Imfinzi

Sterile, preservative free, clear to opalescent and free from visible particles, colourless to slightly yellow.
Each vial of IMFINZI concentrated solution for infusion contains either 120 mg or 500 mg of durvalumab.
Excipients/Inactive Ingredients: Histidine, Histidine hydrochloride monohydrate, Trehalose dihydrate, Polysorbate 80, Water for injection.

Pharmacology: Pharmacodynamics: Mechanism of action: Expression of programmed cell death ligand-1 (PD-L1) protein is an adaptive immune response that helps tumours evade detection and elimination by the immune system. PD-L1 expression can be induced by inflammatory signals (e.g., IFN-gamma) and can be expressed on both tumour cells and tumour-associated immune cells in tumour microenvironment. PD-L1 blocks T-cell function and activation through interaction with PD-1 and CD80 (B7.1). By binding to its receptors, PD-L1 reduces cytotoxic T-cell activity, proliferation, and cytokine production.
Durvalumab is a fully human, high affinity, immunoglobulin G1 kappa (IgG1κ) monoclonal antibody that blocks the interaction of PD-L1 with PD-1 and CD80 (B7.1). Durvalumab does not induce antibody dependent cell-mediated cytotoxicity (ADCC). Blockade of PD-L1/PD-1 and PD-L1/CD80 interactions enhances antitumour immune responses. These antitumour responses may result in tumour elimination.
The combination of tremelimumab, a CTLA-4 inhibitor and durvalumab, a PD-L1 inhibitor functions to enhance anti-tumour T-cell activation and function at multiple stages of the immune response resulting in improved anti-tumour responses. In murine syngeneic tumour models, dual blockade of PD-L1 and CTLA-4 resulted in enhanced anti-tumour activity.
In preclinical studies, PD-L1 blockade by durvalumab led to increased T-cell activation and decreased tumour size in xenograft mouse models of human melanoma and/or pancreatic cancer cells as well as mouse syngeneic colorectal cancer.
Clinical trials: Durvalumab doses of 10 mg/kg every 2 weeks or 1500 mg every 4 weeks were evaluated in NSCLC and ES-SCLC clinical studies. Based on the modelling and simulation of exposure, exposure-safety relationships and exposure-efficacy data comparisons, there are no anticipated clinically significant differences in efficacy and safety between durvalumab doses of 10 mg/kg every 2 weeks or 1500 mg every 4 weeks.
Non-small cell lung cancer (NSCLC): Randomised, placebo-controlled phase 3 study in patients with locally advanced, unresectable NSCLC after chemoradiation (PACIFIC study): The efficacy of IMFINZI was evaluated in the PACIFIC study, a randomised, double-blind, placebo-controlled, multicentre study in 713 patients with histologically or cytologically confirmed locally advanced, unresectable NSCLC. Patients had completed at least 2 cycles of definitive platinum-based chemotherapy with radiation therapy within 1 to 42 days prior to initiation of the study and had an ECOG performance status of 0 or 1. Ninety-two percent of patients had received a total dose of 54 to 66 Gy of radiation. The study excluded patients who had progressed following chemoradiation therapy, patients with prior exposure to any anti-PD-1 or anti-PD-L1 antibody, patients with active or prior documented autoimmune disease within 2 years of initiation of the study; a history of immunodeficiency; a history of severe immune-mediated adverse reactions; medical conditions that required systemic immunosuppression (except physiological dose of systemic corticosteroids); active tuberculosis or hepatitis B or C or HIV infection or patients receiving live attenuated vaccine within 30 days before or after the start of IMFINZI. Patients were randomised 2:1 to receive 10 mg/kg IMFINZI (n=476) or 10 mg/kg placebo (n=237) via intravenous infusion every 2 weeks for up to 12 months or until unacceptable toxicity or confirmed disease progression. Randomisation was stratified by gender, age (<65 years vs. ≥65 years) and smoking status (smoker vs. non- smoker). Patients with disease control at 12 months were given the option to be re-treated upon disease progression. Tumour assessments were conducted every 8 weeks for the first 12 months and then every 12 weeks thereafter.
Patients were enrolled regardless of their tumour PD-L1 expression level. Where available, archival tumour tissue specimens taken prior to chemoradiation therapy were retrospectively tested for PD-L1 expression on tumour cells (TC) using the VENTANA PD-L1 (SP263) IHC assay. Of the 713 patients randomised, 63% of patients provided a tissue sample of sufficient quality and quantity to determine PD-L1 expression and 37% were unknown.
The demographics and baseline disease characteristics were well balanced between study arms. Baseline demographics of the overall study population were as follows: male (70%), age ≥65 years (45%), white (69%), Asian (27%), other (4%), current smoker (16%), past-smoker (75%), and never smoker (9%), WHO/ECOG PS 0 (49%), WHO/ECOG PS 1 (51%). Disease characteristics were as follows: Stage IIIA (53%), Stage IIIB (45%), histological sub-groups of squamous (46%), non-squamous (54%). Of 451 patients with PD L1 expression available, 67% were TC ≥1% [PD-L1 TC 1-24% (32%), PD L1 TC ≥25% (35%)] and 33% were TC <1%.
The two primary endpoints of the study were progression-free survival (PFS) and overall survival (OS) of IMFINZI vs. placebo. Secondary efficacy endpoints included PFS at 12 months (PFS 12) and 18 months (PFS 18) from randomisation and Time from Randomisation to Second Progression (PFS2). PFS was assessed by Blinded Independent Central Review (BICR) according to RECIST 1.1.
The study demonstrated a statistically significant improvement in PFS in the IMFINZI-treated group compared with the placebo group [hazard ratio (HR) = 0.52 (95% CI: 0.42, 0.65), p < 0.0001]. The study demonstrated a statistically significant improvement in OS in the IMFINZI-treated group compared with the placebo group [HR = 0.68 (95% CI: 0.53, 0.87), p=0.00251].
In the 5 year follow-up analysis, with a median follow-up of 34.2 months, IMFINZI continued to demonstrate improved OS and PFS compared to placebo. The OS and PFS results from the primary analysis and the follow-up analysis are summarized in Table 1. Kaplan-Meier curves for OS and PFS from the 5 year follow-up analysis are presented in Figures 1 and 2. (See Table 1 and Figures 1 and 2.)


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The improvements in PFS and OS in favour of patients receiving IMFINZI compared to those receiving placebo were consistently observed in all predefined subgroups analysed, including ethnicity, age, gender, smoking history, EGFR mutation status and histology. ALK mutation status was not analysed in this study.
Post-hoc subgroup analysis by PD-L1 expression: Additional subgroup analyses were conducted to evaluate the efficacy by tumour PD-L1 expression (≥25%, 1-24%, ≥1%, <1%) and for patients whose PD-L1 status could not be established (PD-L1 unknown). PFS and OS results from the 5 year follow-up analysis are summarised in Figures 3 and 4. Overall the safety profile of durvalumab in PD-L1 TC ≥1% subgroup was consistent with the intent to treat population, as was the PD-L1 TC <1% subgroup. (See Figures 3 and 4.)


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Patient reported outcomes: Patient-reported symptoms, function and health-related quality of life (HRQoL) were collected using the EORTC QLQ-C30 and its lung cancer module (EORTC QLQ-LC13). The LC13 and C30 were assessed at baseline and every 4 weeks for the first 8 weeks, then every 8 weeks until completion of the treatment period or discontinuation of study drug due to toxicity or disease progression. Compliance was similar between the IMFINZI and placebo treatment groups (83% vs 85.1% overall of evaluable forms completed).
At baseline, no differences in patient reported symptoms, function or HRQoL were observed between IMFINZI and placebo groups. Throughout the duration of the study to week 48, there was no clinically meaningful difference between IMFINZI and placebo groups in symptoms, functioning and HRQoL (as assessed by a difference of greater than or equal to 10 points).
NSCLC-POSEIDON Study: POSEIDON was a study designed to evaluate the efficacy of IMFINZI with or without tremelimumab in combination with platinum-based chemotherapy. POSEIDON was a randomised, open-label, multicenter study in 1013 metastatic NSCLC patients with no sensitising epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) genomic tumour aberrations. Patients with histologically or cytologically documented metastatic NSCLC were eligible for enrolment. Patients had no prior chemotherapy or any other systemic therapy for metastatic NSCLC. Prior to randomisation, patients had tumour PD-L1 status confirmed by using the Ventana PD-L1 (SP263) assay. Patients had a World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at enrolment.
The study excluded patients with active or prior documented autoimmune disease; active and/or untreated brain metastases; a history of immunodeficiency; administration of systemic immunosuppression within 14 days before the start of IMFINZI or tremelimumab, except physiological dose of systemic corticosteroids; active tuberculosis or hepatitis B or C or HIV infection; or patients receiving live attenuated vaccine within 30 days before or after the start of IMFINZI and/or tremelimumab (see Precautions).
Randomisation was stratified by tumour cells (TC) PD-L1 expression (TC ≥50% vs. TC <50%), disease stage (Stage IVA vs. Stage IVB, per the 8th edition of American Joint Committee on Cancer), and histology (non-squamous vs. squamous).
Patients were randomised 1:1:1 to receive: Arm 1: IMFINZI 1500 mg with tremelimumab 75 mg and platinum-based chemotherapy every 3 weeks for 4 cycles followed by, IMFINZI 1500 mg every 4 weeks as monotherapy. A fifth dose of tremelimumab 75 mg was given at Week 16 alongside IMFINZI dose 6; Arm 2: IMFINZI 1500 mg and platinum-based chemotherapy every 3 weeks for 4 cycles, followed by IMFINZI 1500 mg every 4 weeks as monotherapy; Arm 3: Platinum-based chemotherapy every 3 weeks for 4 cycles. Patients could receive 2 additional cycles (a total of 6 cycles post-randomisation), as clinically indicated, at the Investigator's discretion.
In the 3 treatment arms, patients received one of the following histology-based chemotherapy regimens: Non-squamous NSCLC: Pemetrexed 500 mg/m² with carboplatin AUC 5-6 or cisplatin 75 mg/m² every 3 weeks. Unless contraindicated by the investigator, pemetrexed maintenance could be given.
Squamous NSCLC: Gemcitabine 1000 or 1250 mg/m² on Days 1 and 8 with cisplatin 75 mg/m² or carboplatin AUC 5-6 on Day 1 every 3 weeks.
Non-squamous or squamous NSCLC: Nab-paclitaxel 100 mg/m² on Days 1, 8, and 15 with carboplatin AUC 5-6 on Day 1 every 3 weeks.
Tremelimumab was given up to a maximum of 5 doses unless there was disease progression or unacceptable toxicity. IMFINZI and histology-based pemetrexed maintenance therapy (when applicable) was continued until disease progression or unacceptable toxicity.
Tumour assessments were conducted at Week 6 and Week 12 from the date of randomisation, and then every 8 weeks until confirmed objective disease progression. Survival assessments were conducted every 2 months following treatment discontinuation.
The dual primary endpoints of the study were progression-free survival (PFS) and overall survival (OS) for IMFINZI + platinum-based chemotherapy vs. platinum-based chemotherapy alone. The key secondary endpoints of the study were PFS and OS for IMFINZI + tremelimumab + platinum-based chemotherapy and platinum-based chemotherapy alone. The secondary endpoints included objective response rate (ORR) and Duration of Response (DoR). PFS, ORR, and DoR, were assessed using Blinded Independent Central Review (BICR) according to RECIST v1.1.
The demographics and baseline disease characteristics were well-balanced between study arms. Baseline demographics of the overall study population were as follows: male (76.0%), age ≥65 years (47.1%), age ≥75 years (11.3%) median age 64 years (range: 27 to 87 years), White (55.9%), Asian (34.6%), Black or African American (2.0%), Other (7.6%), non-Hispanic or Latino (84.2%), current smoker or past-smoker (78.0%), WHO/ECOG PS 0 (33.4%), WHO/ECOG PS 1 (66.5%). Disease characteristics were as follows: Stage IVA (50.0%), Stage IVB (49.6%), histological sub-groups of squamous (36.9%), non-squamous (62.9%), brain metastases (10.5%), PD-L1 expression TC ≥50% (28.8%), PD-L1 expression TC <50% (71.1%).
The study showed a statistically significant improvement in OS with IMFINZI + tremelimumab + platinum-based chemotherapy vs. platinum-based chemotherapy. IMFINZI + tremelimumab + platinum-based chemotherapy showed a statistically significant improvement in PFS vs. platinum-based chemotherapy alone. The results are summarised as follows. (See Table 2 and Figures 5 and 6.)


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Figure 7 summarises efficacy results of OS by tumour PD-L1 expression in prespecified subgroup analyses. (See Figure 7.)


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Elderly population: A total of 75 patients aged ≥75 years were enrolled in the IMFINZI in combination with tremelimumab and chemotherapy (n=35) and platinum-based chemotherapy only (n=40) arms of the POSEIDON study. An exploratory HR of 1.05 (95% CI: 0.64, 1.71) for OS was observed for the IMFINZI in combination with tremelimumab and platinum-based chemotherapy vs. platinum-based chemotherapy within this study subgroup. Due to the exploratory nature of this subgroup analysis no definitive conclusions can be drawn, but caution is suggested when considering this regimen for elderly patients.
SCLC-CASPIAN Study: CASPIAN was a study designed to evaluate the efficacy of IMFINZI with or without tremelimumab in combination with etoposide and either carboplatin or cisplatin. CASPIAN was a randomized, open-label, multicenter study in 805 treatment naïve ES-SCLC patients with WHO/ECOG Performance status of 0 or 1, suitable to receive a platinum-based chemotherapy regimen as first-line treatment for SCLC, with life expectancy ≥12 weeks, at least one target lesion by RECIST 1.1 and adequate organ and bone marrow function. Patients with asymptomatic or treated brain metastases were eligible. The study excluded patients with a history of chest radiation therapy; a history of active primary immunodeficiency; autoimmune disorders including paraneoplastic syndrome (PNS); active or prior documented autoimmune or inflammatory disorders; use of systemic immunosuppressants within 14 days before the first dose of the treatment except physiological dose of systemic corticosteroids; active tuberculosis or hepatitis B or C or HIV infection; or patients receiving live attenuated vaccine within 30 days before or after the start of IMFINZI.
Randomisation was stratified by the planned platinum-based therapy in cycle 1 (carboplatin or cisplatin).
Patients were randomised 1:1:1 to receive: Arm 1: IMFINZI 1500 mg + tremelimumab 75 mg + etoposide and either carboplatin or cisplatin; Arm 2: IMFINZI 1500 mg + etoposide and either carboplatin or cisplatin; Arm 3: Either carboplatin (AUC 5 or 6 mg/mL/min) or cisplatin (75-80 mg/m²) on Day 1 and etoposide (80-100 mg/m²) intravenously on Days 1, 2, and 3 of each 21-day cycle for between 4-6 cycles.
For patients randomised to Arm 1 and 2, etoposide and either carboplatin or cisplatin was limited to 4 cycles on an every 3 week schedule subsequent to randomisation. IMFINZI monotherapy continued until disease progression or unacceptable toxicity. Administration of IMFINZI monotherapy was permitted beyond disease progression if the patient was clinically stable and deriving clinical benefit as determined by the investigator.
Patients randomised to Arm 3, were permitted to receive a total of up to 6 cycles of etoposide and either carboplatin or cisplatin. After completion of chemotherapy, prophylactic cranial irradiation (PCI) was permitted only in Arm 3 per investigator discretion.
Tumour assessments were conducted at Week 6 and Week 12 from the date of randomisation, and then every 8 weeks until confirmed objective disease progression. Survival assessments were conducted every 2 months following treatment discontinuation.
The primary endpoints of the study were OS of IMFINZI + chemotherapy (Arm 2) vs. chemotherapy alone (Arm 3) and IMFINZI + tremelimumab + chemotherapy (Arm 1) vs. chemotherapy alone (Arm 3). The key secondary endpoint was PFS. Other secondary endpoints were Objective Response Rate (ORR), OS and PFS landmarks and Patient-Reported Outcomes (PRO). PFS and ORR were assessed using Investigator assessments according to RECIST v1.1.
The demographics and baseline disease characteristics were well balanced between the two study arms (268 patients in Arm 2 and 269 patients in Arm 3). Baseline demographics of the overall study population were as follows: male (69.6%), age ≥65 years (39.6%), median age 63 years (range: 28 to 82 years), white (83.8%), Asian (14.5%), black or African American (0.9%), other (0.6%), non-Hispanic or Latino (96.1%), current or past-smoker (93.1%), never smoker (6.9%), WHO/ECOG PS 0 (35.2%), WHO/ECOG PS 1 (64.8%), Stage IV 90.3%, 24.6% of the patients received cisplatin and 74.1% of the patients received carboplatin. In Arm 3, 56.8% of the patients received 6 cycles of etoposide + platinum and 7.8% of the patients received PCI.
At a planned interim (primary) analysis the study demonstrated a statistically significant improvement in OS with IMFINZI + etoposide + platinum (Arm 2) vs. etoposide + platinum alone (Arm 3) [HR=0.73 (95% CI: 0.591, 0.909), p=0.0047]. IMFINZI + etoposide + platinum demonstrated an improvement in PFS vs. etoposide + platinum alone [HR=0.78 (95% CI: 0.645, 0.936).
The PFS, ORR and DoR results from the planned final analysis (DCO: 27 Jan 2020) are summarized in Table 3. Kaplan-Meier curve for PFS is presented in Figure 9.
The OS results with the planned long-term OS follow-up analysis (DCO: 22 March 2021) (median follow-up: 39.3 months) are presented in Table 3. IMFINZI + etoposide + platinum (Arm 2) vs. etoposide + platinum (Arm 3) continued to demonstrate sustained improvement in OS. Kaplan-Meier curves for OS is presented in Figure 8. (See Table 3 and Figures 8 and 9.)


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Subgroup analysis: The improvements in OS in favor of patients receiving IMFINZI + chemotherapy compared to those receiving chemotherapy alone, were consistently observed across the prespecified subgroups based on demographics, geographical region, carboplatin or cisplatin use and disease characteristics.
BTC-TOPAZ-1 Study: TOPAZ-1 was a study designed to evaluate the efficacy of IMFINZI in combination with gemcitabine and cisplatin. TOPAZ-1 was a randomised, double-blind, placebo-controlled, multicentre study in 685 patients with unresectable or metastatic BTC (including intrahepatic and extrahepatic cholangiocarcinoma and gallbladder carcinoma) and ECOG Performance status of 0 or 1. Patients had not received previous therapy in the advanced/unresectable setting. Patients who developed recurrent disease > 6 months after surgery and/or completion of adjuvant therapy were included. Patients must have had an adequate organ and bone marrow function, and have had acceptable serum bilirubin levels (≤2.0 x the upper limit of normal (ULN)), and any clinically significant biliary obstruction had to be resolved before randomisation.
The study excluded patients with ampullary carcinoma, with brain metastases, active or prior documented autoimmune or inflammatory disorders, HIV infection or active infections, including tuberculosis or hepatitis C or patients with current or prior use of immunosuppressive medication within 14 days before the first dose of IMFINZI. Patients with active HBV were allowed to participate if they were on antiviral therapy.
Randomisation was stratified by disease status (initially unresectable vs. recurrent) and primary tumour location (intrahepatic cholangiocarcinoma vs. extrahepatic cholangiocarcinoma vs. gallbladder carcinoma).
Patients were randomised 1:1 to receive: Arm 1: IMFINZI 1500 mg administered on Day 1 + gemcitabine 1000 mg/m² and cisplatin 25 mg/m² (each administered on Days 1 and 8) every 3 weeks (21 days) for up to 8 cycles, followed by IMFINZI 1500 mg every 4 weeks until disease progression or unacceptable toxicity, or; Arm 2: Placebo administered on Day 1 + gemcitabine 1000 mg/m² and cisplatin 25 mg/m² (each administered on Days 1 and 8) every 3 weeks (21 days) for up to 8 cycles, followed by placebo every 4 weeks until disease progression or unacceptable toxicity.
Tumour assessments were conducted every 6 weeks for the first 24 weeks after the date of randomisation, and then every 8 weeks until confirmed objective disease progression.
The primary endpoint of the study was OS, the key secondary endpoint was PFS. Other secondary endpoints were ORR, Duration of Response (DoR) and PRO. PFS, ORR and DoR were investigator-assessed according to RECIST v1.1.
The demographics and baseline disease characteristics were well balanced between the two study arms (341 patients in Arm 1 and 344 patients in Arm 2). Baseline demographics of the overall study population were as follows: male (50.4%), age <65 years (53.3%), white (37.2%), Asian (56.4%), Black or African American (2.0%), other (4.2%), non-Hispanic or Latino (93.1%), ECOG PS 0 (49.1%), vs. PS 1 (50.9%), primary tumour location (intrahepatic bile duct 55.9%, extrahepatic bile duct 19.1% and gallbladder 25.0%), disease status [recurrent (19.1%) vs. unresectable (80.7%), metastatic (86.0%) vs. locally advanced (13.9%)]. PD-L1 expression was evaluated on tumour and immune cells using the Ventana PD-L1 (SP263) assay and the TAP (tumour area positivity) algorithm, 58.7% patients had TAP ≥1% and 30.1% TAP <1%.
OS and PFS were formally tested at a pre-planned interim analysis (data cut-off 11 Aug 2021) after a median follow-up of 9.8 months. Efficacy results are shown in Table 4 and Figure 10. The maturity for OS was 62% and the maturity for PFS was 84%. IMFINZI + chemotherapy (Arm 1) showed statistically significant improvement vs. placebo + chemotherapy (Arm 2) in OS and in PFS. (See Table 4.)


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An additional planned follow-up analysis of OS (data cut-off 25 Feb 2022) was performed 6.5 months after the interim analysis with an OS maturity of 77%. IMFINZI + chemotherapy continued to demonstrate improved OS vs. chemotherapy alone [HR=0.76, (95% CI: 0.64, 0.91)] and the medium follow-up increased to 12 months. (See Figures 10 and 11.)


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HCC-HIMALAYA Study: The efficacy of IMFINZI given in combination with a single dose of tremelimumab 300 mg was evaluated in the HIMALAYA Study, a randomised, open-label, multicentre study in patients with confirmed uHCC who did not receive prior systemic treatment for HCC. The study included patients with Barcelona Clinic Liver Cancer (BCLC) Stage C or B (not eligible for locoregional therapy) and Child-Pugh Score Class A.
The study excluded patients with brain metastases or a history of brain metastases, co-infection of viral hepatitis B and hepatitis C; active or prior documented gastrointestinal (GI) bleeding within 12 months; ascites requiring non-pharmacologic intervention within 6 months; hepatic encephalopathy within 12 months before the start of treatment; active or prior documented autoimmune or inflammatory disorders.
Patients with oesophageal varices were included except those with active or prior documented GI bleeding within 12 months prior to study entry.
Randomisation was stratified by macrovascular invasion (MVI) (yes vs. no), aetiology of liver disease (confirmed hepatitis B virus vs. confirmed hepatitis C virus vs. others) and ECOG performance status (0 vs. 1). The HIMALAYA study randomized 1171 patients 1:1:1 to receive: IMFINZI: durvalumab 1500 mg every 4 weeks; Tremelimumab 300 mg as a single dose + IMFINZI 1500 mg; followed by IMFINZI 1500 mg every 4 weeks; S: Sorafenib 400 mg twice daily.
Tumour assessments were conducted every 8 weeks for the first 12 months and then every 12 weeks thereafter. Survival assessments were conducted every month for the first 3 months following treatment discontinuation and then every 2 months.
The primary endpoint was OS. Secondary endpoints included PFS, Investigator-assessed ORR and DoR according to RECIST v1.1.
The demographics and baseline disease characteristics were well balanced between study arms. The baseline demographics of the overall study population were as follows: male (83.7%), age <65 years (50.4%) White (44.6%), Asian (50.7%), Black or African American (1.7%), Other race (2.3%), ECOG PS 0 (62.6%); Child-Pugh Class score A (99.5%), macrovascular invasion (25.2%), extrahepatic spread (53.4%), baseline AFP <400 ng/mL (63.7%), baseline AFP ≥ 400 ng/mL (34.5%), viral aetiology; hepatitis B (30.6%), hepatitis C (27.2%), uninfected (42.2%), evaluable PD-L1 data (86.3%), PD-L1 Tumour area positivity (TAP) ≥1% (38.9%), PD-L1 TAP <1% (48.3%) [Ventana PD-L1 (SP263) assay].
Results are presented in Table 5 and Figure 12. (See Table 5 and Figure 12.)


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Pharmacokinetics: The pharmacokinetics (PK) of durvalumab was assessed for IMFINZI as a single agent, in combination with chemotherapy, in combination with tremelimumab and platinum-based chemotherapy and in combination with tremelimumab.
The PK of durvalumab was studied in 2903 patients with solid tumours with doses ranging from 0.1 to 20 mg/kg administered intravenously once every two, three or four weeks as monotherapy. PK exposure increased more than dose-proportionally (non-linear PK) at doses <3 mg/kg, and dose proportionally (linear PK) at doses ≥3 mg/kg. Steady state was achieved at approximately 16 weeks. Based on population PK analysis that included 1878 patients who received durvalumab monotherapy in the dose range of ≥10 mg/kg every 2 weeks, the geometric mean steady state volume of distribution (V_ss) was 5.64 L. Durvalumab clearance (CL) decreased over time resulting in a geometric mean steady state clearance (CL_ss) of 8.16 mL/h at Day 365; the decrease in CLss was not considered clinically relevant. The terminal half-life (t_1/2), based on baseline CL, was approximately 18 days. There was no clinically meaningful difference between the PK of durvalumab as a single agent, in combination with chemotherapy, in combination with tremelimumab and platinum-based chemotherapy and in combination with tremelimumab. The primary elimination pathways of durvalumab are protein catabolism via reticuloendothelial system or target mediated disposition.
Special populations: Age (19-96 years), body weight (31-149 kg), gender, positive anti-drug antibody (ADA) status, albumin levels, LDH levels, creatinine levels, soluble PD-L1, tumour type, race or ECOG status had no clinically significant effect on the PK of durvalumab.
Renal impairment: Mild (creatinine clearance (CrCL) 60 to 89 mL/min) and moderate renal impairment (creatinine clearance (CrCL) 30 to 59 mL/min) had no clinically significant effect on the PK of durvalumab. The effect of severe renal impairment (CrCL 15 to 29 mL/min) on the PK of durvalumab is unknown; however, as IgG monoclonal antibodies are not primarily cleared via renal pathways, a change in renal function is not expected to influence durvalumab exposure.
Hepatic impairment: Mild hepatic impairment (bilirubin ≤ULN and AST >ULN or bilirubin >1.0 to 1.5 x ULN and any AST) or moderate hepatic impairment (bilirubin >1.5 to 3 x ULN and any AST) had no clinically significant effect on the PK of durvalumab. The effect of severe hepatic impairment (bilirubin >3.0 x ULN and any AST) on the pharmacokinetics of durvalumab is unknown; however, as IgG monoclonal antibodies are not primarily cleared via hepatic pathways, a change in hepatic function is not expected to influence durvalumab exposure.
Toxicology: Preclinical safety data: Genotoxicity: The genotoxic potential of durvalumab has not been evaluated. As a large protein molecule, durvalumab is not expected to interact directly with DNA or other chromosomal material.
Carcinogenicity: The carcinogenic potential of durvalumab has not been evaluated.

Locally advanced non-small cell lung cancer (NSCLC): IMFINZI (durvalumab) is indicated for the treatment of patients with locally advanced, unresectable NSCLC whose disease has not progressed following platinum-based chemoradiation therapy.
IMFINZI in combination with tremelimumab and platinum-based chemotherapy is indicated for treatment of adults with metastatic NSCLC with no sensitising EGFR mutations or ALK positive mutations.
Small Cell Lung Cancer (SCLC): IMFINZI in combination with etoposide and either carboplatin or cisplatin is indicated for the first-line treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC).
Biliary Tract Cancer (BTC): IMFINZI in combination with gemcitabine and cisplatin is indicated for treatment of adults with unresectable or metastatic biliary tract cancer (BTC).
Hepatocellular Carcinoma (HCC): IMFINZI in combination with tremelimumab is indicated for treatment of adults with advanced or unresectable hepatocellular carcinoma (HCC).

IMFINZI is for single use in one patient only. Discard any residue.
Posology: The recommended dose for IMFINZI monotherapy and IMFINZI combination therapy is presented in Table 6. IMFINZI is administered as an intravenous infusion over 1 hour. (See Table 6.)


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Dose escalation or reduction is not recommended. Treatment withholding, or discontinuation may be required based on individual safety and tolerability, see Table 7.
Guidelines for management of adverse reactions are described in Table 7. When used in combination with tremelimumab refer also to the SmPc for tremelimumab. (See Table 7.)


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For suspected immune-mediated adverse reactions, adequate evaluation should be performed to confirm aetiology or exclude alternate aetiologies. Based on the severity of the adverse reaction, IMFINZI and/or tremelimumab should be withheld and corticosteroids administered. Consider increasing dose of corticosteroids and/or using additional systemic immunosuppressants if there is worsening or no improvement. Upon improvement to ≤ Grade 1, corticosteroid taper should be initiated and continued over at least 1 month. After withhold, IMFINZI and/or tremelimumab can be resumed within 12 weeks if the adverse reactions improved to ≤ Grade 1 and the corticosteroid dose has been reduced to ≤10 mg prednisone or equivalent per day. IMFINZI and tremelimumab should be permanently discontinued for recurrent Grade 3 (severe) immune-mediated adverse reactions and for any Grade 4 (life-threatening) immune-mediated adverse reactions, except for endocrinopathies that are controlled with replacement hormones.
Special patient populations: Renal impairment: No dose adjustment of IMFINZI is recommended for patients with mild or moderate renal impairment (see Pharmacology: Pharmacokinetics under Actions). Durvalumab has not been studied in subjects with severe renal impairment.
Hepatic impairment: No dose adjustment of IMFINZI is recommended for patients with mild or moderate hepatic impairment. Data from patients with moderate and severe hepatic impairment are too limited to draw conclusions on this population (see Pharmacology: Pharmacokinetics under Actions).
Use in paediatric patients: The safety and efficacy of durvalumab have not been established in patients younger than 18 years of age.
Use in the elderly: No dose adjustment is required for elderly patients (≥65 years of age) (see Pharmacology: Pharmacodynamics: Clinical trials and Pharmacokinetics under Actions).
Method of administration: IMFINZI is for intravenous use. It is to be administered as an intravenous infusion solution over 1 hour.
IMFINZI in combination with chemotherapy: When IMFINZI is administered in combination with chemotherapy, administer IMFINZI prior to chemotherapy on the same day.
IMFINZI in combination with tremelimumab and platinum-based chemotherapy: When IMFINZI is administered in combination with tremelimumab and platinum-based chemotherapy, tremelimumab is given first, followed by IMFINZI and then platinum-based chemotherapy on the same day of dosing.
When IMFINZI is administered in combination with a fifth dose of tremelimumab and pemetrexed maintenance therapy at week 16, tremelimumab is given first, followed by IMFINZI and then pemetrexed maintenance therapy on the same day of dosing.
IMFINZI, tremelimumab, and platinum-based chemotherapy are administered as separate intravenous infusions. IMFINZI and tremelimumab are each given over 1 hour. For platinum-based chemotherapy, refer to the SmPC for administration information. For pemetrexed maintenance therapy, refer to the SmPC for administration information. Separate infusion bags and filters for each infusion should be used.
During cycle 1, tremelimumab is to be followed by IMFINZI starting approximately 1 hour (maximum 2 hours) after the end of the tremelimumab infusion. Platinum-based chemotherapy infusion should start approximately 1 hour (maximum 2 hours) after the end of the IMFINZI infusion. If there are no clinically significant concerns during cycle 1, then at the physician's discretion, subsequent cycles of IMFINZI can be given immediately after tremelimumab and the time period between the end of the IMFINZI infusion and the start of chemotherapy can be reduced to 30 minutes.
IMFINZI in combination with tremelimumab: When IMFINZI is administered in combination with tremelimumab, administer tremelimumab prior to IMFINZI on the same day. IMFINZI and tremelimumab are administered as separate intravenous infusions. Refer to the summary of product characteristics (SmPC) for tremelimumab dosing information.
Preparation of solution: IMFINZI is supplied as single-dose vials and does not contain any preservatives. Aseptic technique must be observed.
Visually inspect drug product for particulate matter and discolouration. IMFINZI is a clear to opalescent, colourless to slightly yellow solution. Discard the vial if the solution is cloudy, discoloured or visible particles are observed. Do not shake the vial.
Withdraw the required volume from the vial(s) of IMFINZI and transfer into an intravenous (IV) bag containing 0.9% Sodium Chloride Injection, or 5% Dextrose Injection. Mix diluted solution by gentle inversion. The final concentration of the diluted solution should be between 1 mg/mL and 15 mg/mL. Do not freeze or shake the solution.
Care must be taken to ensure the sterility of prepared solutions.
Do not re-enter the vial after withdrawal of drug; only withdraw one dose per vial.
Discard any unused portion left in the vial.
No incompatibilities between IMFINZI and 9 g/L (0.9%) sodium chloride or 50 g/L (5%) dextrose in polyvinylchloride or polyolefin IV bags have been observed.
After preparation of infusion solution: IMFINZI does not contain a preservative.
Chemical and physical in-use stability has been demonstrated for up to 30 days at 2ºC to 8ºC and for up to 24 hours at room temperature (up to 25ºC) from the time of preparation.
From a microbiological point of view, the prepared solution for infusion should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2ºC to 8ºC or 12 hours at room temperature (up to 25ºC), unless dilution has taken place in controlled and validated aseptic conditions.
Administration: Administer infusion solution intravenously over 60 minutes through an intravenous line containing a sterile, low-protein binding 0.2 or 0.22 micron in-line filter.
Do not co-administer other drugs through the same infusion line.

There is no specific treatment in the event of durvalumab overdose, and symptoms of overdose are not established. In the event of an overdose, physicians should follow general supportive measures and should treat symptomatically.

Hypersensitivity to the active substance or to any of the excipients listed in Description.

Traceability: In order to improve the traceability of biological medicinal products, the tradename and the batch number of the administered product should be clearly recorded.
Immune-mediated pneumonitis: Immune-mediated pneumonitis or interstitial lung disease, defined as requiring use of systemic corticosteroids and with no clear alternate aetiology, occurred in patients receiving IMFINZI or IMFINZI in combination with tremelimumab (see Adverse Reactions).
Pneumonitis and radiation pneumonitis: Radiated pneumonitis is frequently observed in patients receiving radiation therapy to the lung and the clinical presentation of pneumonitis and radiation pneumonitis is very similar. In the PACIFIC Study, in patients who had completed treatment with at least 2 cycles of concurrent chemoradiation within 1 to 42 days prior to initiation of the trial, pneumonitis or radiation pneumonitis occurred in 161 (33.9%) patients in the IMFINZI-treated group and 58 (24.8%) in the placebo group, including Grade 3 (3.4% vs 3.0%) and Grade 5 (1.1% vs 1.7%).
Patients should be monitored for signs and symptoms of pneumonitis. Suspected pneumonitis should be confirmed with radiographic imaging and other infectious and disease-related aetiologies excluded, and managed as recommended in Dosage & Administration.
Immune-mediated hepatitis: Immune-mediated hepatitis, defined as requiring use of systemic corticosteroids and with no clear alternate aetiology, occurred in patients receiving IMFINZI or IMFINZI in combination with tremelimumab (see Adverse Reactions). Monitor alanine aminotransferase, aspartate aminotransferase, total bilirubin, and alkaline phosphatase levels prior to initiation of treatment and prior to each subsequent infusion. Additional monitoring is to be considered based on clinical evaluation Immune-mediated hepatitis should be managed as recommended in Dosage & Administration.
Immune-mediated colitis: Immune-mediated colitis or diarrhoea, defined as requiring use of systemic corticosteroids and with no clear alternate aetiology, occurred in patients receiving IMFINZI or IMFINZI in combination with tremelimumab (see Adverse Reactions). Adverse drug reactions of intestinal perforation and large intestine perforation were reported in patients receiving IMFINZI in combination with tremelimumab. Patients should be monitored for signs and symptoms of colitis/diarrhoea and intestinal perforation and managed as recommended in Dosage & Administration.
Immune-mediated endocrinopathies: Immune-mediated hypothyroidism/hyperthyroidism/thyroiditis: Immune-mediated hypothyroidism, hyperthyroidism, or thyroiditis occurred in patients receiving IMFINZI or IMFINZI in combination with tremelimumab, and hypothyroidism may follow hyperthyroidism (see Adverse Reactions). Patients should be monitored for abnormal thyroid function tests prior to and periodically during treatment as indicated based on clinical evaluation. Immune-mediated hypothyroidism, hyperthyroidism, and thyroiditis should be managed as recommended in Dosage & Administration.
Immune-mediated adrenal insufficiency: Immune-mediated adrenal insufficiency occurred in patients receiving IMFINZI or IMFINZI in combination with tremelimumab (see Adverse Reactions). Patients should be monitored for clinical signs and symptoms of adrenal insufficiency. For symptomatic adrenal insufficiency, patients should be managed as recommended in Dosage & Administration.
Immune-mediated type 1 diabetes mellitus, which can first present as diabetic ketoacidosis that can be fatal if not detected early, occurred in patients receiving IMFINZI or IMFINZI in combination with tremelimumab (see Adverse Reactions). Patients should be monitored for clinical signs and symptoms of type 1 diabetes mellitus. For symptomatic type 1 diabetes mellitus, patients should be managed as recommended in Dosage & Administration.
Immune-mediated hypophysitis/hypopituitarism: Immune-mediated hypophysitis/hypopituitarism occurred in patients receiving IMFINZI or IMFINZI in combination with tremelimumab (see Adverse Reactions). Patients should be monitored for clinical signs and symptoms of hypophysitis. For symptomatic hypophysitis or hypopituitarism, patients should be managed as recommended in Dosage & Administration.
Immune-mediated nephritis: Immune-mediated nephritis, defined as requiring use of systemic corticosteroids and with no clear alternate aetiology, occurred in patients receiving IMFINZI or IMFINZI in combination with tremelimumab (see Adverse Reactions). Patients should be monitored for abnormal renal function tests prior to and periodically during treatment with IMFINZI or IMFINZI in combination with tremelimumab and managed as recommended in Dosage & Administration.
Immune-mediated rash: Immune-mediated rash or dermatitis (including pemphigoid), defined as requiring use of systemic corticosteroids and with no clear alternate aetiology, occurred in patients receiving IMFINZI or IMFINZI in combination with tremelimumab see Adverse Reactions. Events of Stevens-Johnson Syndrome (SJS) or toxic epidermal necrolysis have been reported in patients treated with PD-1 inhibitors. Patients should be monitored for signs and symptoms of rash or dermatitis and managed as recommended in Dosage & Administration.
Immune-mediated myocarditis: Immune-mediated myocarditis, which can be fatal, occurred in patients receiving IMFINZI or IMFINZI in combination with tremelimumab (see Adverse Reactions). Patients should be monitored for signs and symptoms of immune-mediated myocarditis and managed as recommended in Dosage & Administration.
Immune-mediated pancreatitis: Immune-mediated pancreatitis, occurred in patients receiving IMFINZI in combination with tremelimumab and chemotherapy (see Adverse Reactions). Patients should be monitored for signs and symptoms of immune-mediated pancreatitis and managed as recommended in Dosage & Administration.
Other immune mediated adverse reactions: Given the mechanism of action of IMFINZI or IMFINZI in combination with tremelimumab, other potential immune-mediated adverse reactions may occur. The following immune-related adverse reactions have been observed in patients treated with IMFINZI monotherapy or IMFINZI in combination with tremelimumab: myasthenia gravis, myositis, polymyositis, meningitis, Guillain-Barré syndrome, immune thrombocytopenia and pancreatitis (see Adverse Reactions). Events of pancreatitis have been reported in patients in the clinical study programme. Patients should be monitored for signs and symptoms and managed as recommended in Dosage & Administration.
Infusion-related reactions: Patients should be monitored for signs and symptoms of infusion-related reactions. Severe infusion related reactions have been reported in patients receiving IMFINZI or IMFINZI in combination with tremelimumab (see Adverse Reactions). Infusion-related reactions should be managed as recommended in Dosage & Administration.
Disease-specific precaution (BTC): Cholangitis and biliary tract infections: Cholangitis and biliary tract infections are not uncommon in patients with advanced BTC. Cholangitis events were reported in TOPAZ-1 in both treatment groups (14.5% [IMFINZI + chemotherapy] vs. 8.2% [placebo + chemotherapy]); these were mostly in association with biliary stents and were not immune-mediated in aetiology. Patients with BTC (especially those with biliary stents) should be closely monitored for development of cholangitis or biliary tract infections before initiation of treatment and, regularly, thereafter.
Metastatic NSCLC: Limited data are available in elderly patients (≥75 years) treated with IMFINZI in combination with tremelimumab and platinum-based chemotherapy (see Adverse Reactions and Pharmacology: Pharmacodynamics under Actions). Careful consideration of the potential benefit/risk of this regimen on an individual basis is recommended.
Patients excluded from clinical trials: Patients with the following were excluded from clinical trials: a baseline ECOG performance score ≥2; active or prior documented autoimmune disease within 2 years of initiation of the study; a history of immunodeficiency; a history of severe immune-mediated adverse reactions; medical conditions that required systemic immunosuppression, except physiological dose of systemic corticosteroids (≤10 mg/day prednisone or equivalent); uncontrolled intercurrent illnesses; active tuberculosis or hepatitis B or C or HIV infection or patients receiving live attenuated vaccine within 30 days before or after the start of IMFINZI. In the absence of data, durvalumab should be used with caution in these populations after careful consideration of the potential benefit/risk on an individual basis. The safety of concurrent prophylactic cranial irradiation (PCI) with IMFINZI in patients with ES-SCLC is unknown.
For more information on exclusion criteria for each specific study see Pharmacology: Pharmacodynamics under Actions.
Effects on ability to drive and use machines: Based on its pharmacodynamic properties, durvalumab is unlikely to affect the ability to drive and use machines. However, if patients experience adverse reactions affecting their ability to concentrate and react, they should be advised to use caution when driving or operating machinery.

Effects on fertility: There are no data on the effects of durvalumab on fertility in humans. In repeat-dose toxicology studies of durvalumab up to 3 months duration in sexually mature cynomolgus monkeys, there were no notable effects on the male and female reproductive organs. These animals received weekly doses of durvalumab yielding 23 times the exposure (based on AUC) in humans at the recommended clinical dose.
Use in pregnancy - Category D: There are no data on the use of durvalumab in pregnant women. Based on its mechanism of action, durvalumab has the potential to impact maintenance of pregnancy and may cause foetal harm when administered to a pregnant woman. Human IgG1 is known to cross the placental barrier; therefore, durvalumab has the potential to be transmitted from the mother to the developing foetus.
Durvalumab use is not recommended during pregnancy. Women of childbearing potential should use effective contraception during treatment and for at least 3 months after the last dose.
Animal data: As reported in the literature, the PD-1/PD-L1 pathway plays a central role in preserving pregnancy by maintaining maternal immune tolerance to the foetus. In mouse allogeneic pregnancy models, disruption of PD-L1 signalling was shown to result in an increase in foetal loss. The effects of durvalumab on prenatal and postnatal development were evaluated in reproduction studies in cynomolgus monkeys. Durvalumab was administered from the confirmation of pregnancy through delivery at exposure levels approximately 6 to 20 times higher than those observed in humans at the recommended clinical dose of 10 mg/kg (based on AUC). Administration of durvalumab resulted in premature delivery, foetal loss (abortion and stillbirth) and increase in neonatal deaths compared to concurrent controls. Durvalumab was detected in infant serum on postpartum Day 1, indicating the presence of placental transfer of durvalumab. Based on its mechanism of action, foetal exposure to durvalumab may increase the risk of developing immune-mediated disorders or altering the normal immune response and immune-mediated disorders have been reported in PD-1 knockout mice.
Use in lactation: There is no information regarding the presence of durvalumab in human milk, the absorption and effects on the breastfed infant, or the effects on milk production. Human IgG is excreted in human milk. In animal reproduction studies, administration of durvalumab to pregnant cynomolgus monkeys was associated with dose-related low-level excretion of durvalumab in breast milk and was associated with premature neonatal death compared to concurrent controls. Because of the potential for adverse reactions in breastfed infants from durvalumab, lactating women should be advised not to breastfeed during treatment and for at least 3 months after the last dose.

Summary of the safety profile: IMFINZI as monotherapy: The safety of IMFINZI as monotherapy is based on pooled data in 3006 patients across multiple tumour types. IMFINZI was administered at a dose of 10 mg/kg every 2 weeks or 20 mg/kg every 4 weeks. The most common (>10%) adverse reactions were cough/productive cough (21.5%), diarrhoea (16.3%), rash (16.0%), pyrexia (13.8%), upper respiratory tract infections (13.5%), abdominal pain (12.7%), pruritus (10.8%), and hypothyroidism (10.1%). The most common (>2%) Grade ≥3 adverse reactions were pneumonia (3.5%) and aspartate aminotransferase increased/alanine aminotransferase increased (2.3%).
IMFINZI was discontinued due to adverse reactions in 3.6% of patients. The most common adverse reaction leading to treatment discontinuation was pneumonitis (1.1%) and pneumonia (0.8%).
IMFINZI was delayed or interrupted due to adverse reactions in 13.7% of patients. The most common adverse reactions leading to dose delay or interruption were pneumonia (2.7%) and aspartate aminotransferase increased/alanine aminotransferase increased (1.7%).
IMFINZI in combination with chemotherapy: The safety of IMFINZI in combination with chemotherapy is based on pooled data in 603 patients from 2 studies (TOPAZ-1 and CASPIAN). The most common (>10%) adverse reactions were neutropenia (53.1%), anaemia (43.9%), nausea (37.5%), fatigue (36.8%), thrombocytopenia (28.0%), constipation (25.4%), decreased appetite (22.6%), abdominal pain (18.4%), alopecia (18.4%), leukopenia (17.2%), vomiting (16.9%), pyrexia (15.1%), rash (14.8%), diarrhoea (13.8%), aspartate aminotransferase increased or alanine aminotransferase increased (10.9%), cough/productive cough (10.8%), and pruritus (10.4%).
The most common (>2%) Grade ≥ 3 adverse reactions were neutropenia (35.2%), anaemia (17.4%), thrombocytopenia (11.1%), leukopenia (7.1%), fatigue (5.0%), febrile neutropenia (3.0%), aspartate aminotransferase increased or alanine aminotransferase increased (2.8%) and pneumonia (2.5%).
IMFINZI was discontinued due to adverse reactions in 2.0% of patients. The most common adverse reaction leading to treatment discontinuation was fatigue (0.3%).
IMFINZI was delayed or interrupted due to adverse reactions in 29.2% of patients. The most common adverse reactions leading to dose delay or interruption were neutropenia (17.1%), anaemia (3.8%), thrombocytopenia (4.3%), leukopenia (3.5%), fatigue (1.7%) and pyrexia (1.3).
IMFINZI in combination with tremelimumab 75 mg and platinum-based chemotherapy: The safety of IMFINZI given in combination with tremelimumab 75 mg and chemotherapy is based on data in 330 patients with metastatic NSCLC. The most common (>20%) adverse reactions were anaemia (49.7%), nausea (41.5%), neutropenia (41.2%), fatigue (36.1%), rash (25.8%), thrombocytopenia (24.5%) and diarrhoea (21.5%). The most common (>2%) Grade ≥ 3 adverse reactions were neutropenia (23.9%), anaemia (20.6%), pneumonia (9.4%), thrombocytopenia (8.2%), leukopenia (5.5%), fatigue (5.2%), lipase increased (3.9%), amylase increased (3.6%), febrile neutropenia (2.4%), colitis (2.1%) and aspartate aminotransferase increased/alanine aminotransferase increased (2.1%).
IMFINZI was discontinued due to adverse reactions in 8.5% of patients. The most common adverse reactions leading to treatment discontinuation were pneumonia (2.1%) and colitis (1.2%).
IMFINZI was interrupted due to adverse reactions in 49.4% of patients. The most common adverse reactions leading to dose interruption were neutropenia (16.1%), anaemia (10.3%), thrombocytopenia (7.3%), leukopenia (5.8%), pneumonia (5.2%), aspartate aminotransferase increased/alanine aminotransferase increased (4.8%), colitis (3.3%) and pneumonitis (3.3%).
IMFINZI in combination with tremelimumab 300 mg: The safety of IMFINZI given in combination with a single dose of tremelimumab 300 mg is based on pooled data (HCC pool) in 462 HCC patients from the HIMALAYA Study and another study in HCC patients, Study 22. The most common (>10%) adverse reactions were rash (32.5%), pruritus (25.5%), diarrhoea (25.3%), abdominal pain (19.7%), aspartate aminotransferase increased/alanine aminotransferase increased (18.0%), pyrexia (13.9%), hypothyroidism (13.0%), cough/productive cough (10.8%), oedema peripheral (10.4%) and lipase increased (10.0%) (see Table 8). The most common severe adverse reactions (NCI CTCAE Grade ≥3) are aspartate aminotransferase increased/alanine aminotransferase increased (8.9%), lipase increased (7.1%), amylase increased (4.3%) and diarrhoea (3.9%).
The most common serious adverse reactions are colitis (2.6%), diarrhoea (2.4%), pneumonia (2.2%), and hepatitis (1.7%).
The frequency of treatment discontinuation due to adverse reactions is 6.5%. The most common adverse reactions leading to treatment discontinuation are hepatitis (1.5%) and aspartate aminotransferase increased/alanine aminotransferase increased (1.3%).
The severity of adverse drug reactions was assessed based on the CTCAE, defining grade 1=mild, grade 2=moderate, grade 3=severe, grade 4=life threatening and grade 5=death.
Tabulated list of adverse reactions: Table 8 lists the incidence of adverse reactions in the IMFINZI monotherapy pooled safety dataset and in patients treated with IMFINZI in combination with chemotherapy (N=603) Unless otherwise stated, Table 4 lists the incidence of adverse reactions in patients treated with IMFINZI in combination with tremelimumab 75 mg and platinum-based chemotherapy in the POSEIDON study (N=330) and in patients treated with IMFINZI in combination with a single dose of tremelimumab 300 mg in the HCC pool (N=462). Adverse reactions are listed according to system organ class in MedDRA. Within each system organ class, the adverse reactions are presented in decreasing frequency. The corresponding frequency category for each ADR is defined as: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1000); very rare (<1/10,000); not known (cannot be estimated from available data). Within each frequency grouping, adverse drug reactions are presented in order of decreasing seriousness. (See Tables 8 and 9.)


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Description of selected adverse reactions: IMFINZI is associated with immune-mediated adverse reactions. Most of these, including severe reactions, resolved following initiation of appropriate medical therapy or withdrawal and/or treatment modifications. The data for the following immune-mediated adverse reactions reflect IMFINZI monotherapy the combined safety database of 3006 patients which includes the PACIFIC Study and additional studies in patients with various solid tumours, in indications for which durvalumab is not approved. Across all studies, IMFINZI was administered at a dose of 10 mg/kg every 2 weeks, 20 mg/kg every 4 weeks, or 1500 mg every 3 or 4 weeks. Details for the significant adverse reactions for IMFINZI when given in combination with chemotherapy are presented if clinically relevant differences were noted in comparison to IMFINZI monotherapy.
The data for the following immune-mediated adverse reactions are also based on 2280 patients who received IMFINZI 20 mg/kg every 4 weeks in combination with tremelimumab 1 mg/kg or IMFINZI 1500 mg in combination with tremelimumab 75 mg every 4 weeks. Details for the significant adverse reactions for IMFINZI when given in combination with tremelimumab and platinum-based chemotherapy are presented if clinically relevant differences were noted in comparison to IMFINZI in combination with tremelimumab.
The data for the following immune-mediated adverse reactions also reflect the IMFINZI in combination with tremelimumab 300 mg combined safety database of 462 patients with HCC (the HCC pool). In these two studies, IMFINZI was administered at a dose of 1500 mg in combination with tremelimumab 300 mg every 4 weeks.
The management guidelines for these adverse reactions are described in Dosage & Administration and Precautions.
Immune-mediated pneumonitis: In the combined safety database with IMFINZI monotherapy, (n=3006 multiple tumour types), immune-mediated pneumonitis occurred in 92 (3.1%) patients, including Grade 3 in 25 (0.8%) patients, Grade 4 in 2 (<0.1%) patient, and Grade 5 in 6 (0.2%) patients. The median time to onset was 55 days (range: 2-785 days). Sixty-nine of the 92 patients received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day), and 2 patients also received infliximab and 1 patient also received cyclosporine. IMFINZI was discontinued in 38 patients. Resolution occurred in 53 patients.
Immune-mediated pneumonitis occurred more frequently in the PACIFIC study who had completed treatment with concurrent chemoradiation within 1 to 42 days prior to initiation of the study (9.9%), than in the other patients in the combined safety database (1.8%).
In the PACIFIC Study, (n=475 in the IMFINZI arm, and n=234 in the placebo arm) immune-mediated pneumonitis occurred in 47 (9.9%) patients in the IMFINZI-treated group and 14 (6.0%) patients in the placebo group, including Grade 3 in 9 (1.9%) patients on IMFINZI vs. 6 (2.6%) patients on placebo and Grade 5 (fatal) in 4 (0.8%) patients on IMFINZI vs. 3 (1.3%) patients on placebo. The median time to onset in the IMFINZI-treated group was 46 days (range: 2-342 days) vs. 57 days (range: 26-253 days) in the placebo group. In the IMFINZI-treated group, all patients received systemic corticosteroids, including 30 patients who received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day), and 2 patients also received infliximab. In the placebo group, all patients received systemic corticosteroids, including 12 patients who received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day) and 1 patient also received cyclophosphamide and tacrolimus. Resolution occurred for 29 patients in the IMFINZI treated group vs. 6 in placebo.
In the combined safety database with IMFINZI in combination with tremelimumab (n=2280), immune-mediated pneumonitis occurred in 86 (3.8%) patients, including Grade 3 in 30 (1.3%) patients, Grade 4 in 1 (<0.1%) patient, and Grade 5 (fatal) in 7 (0.3%) patients. The median time to onset was 57 days (range: 8-912 days). All patients received systemic corticosteroids and 79 of the 86 patients received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). Seven patients also received other immunosuppressants. Treatment was discontinued in 39 patients. Resolution occurred in 51 patients.
In the HCC pool (n=462), immune-mediated pneumonitis occurred in 6 (1.3%) patients, including Grade 3 in 1 (0.2%) patient and Grade 5 (fatal) in 1 (0.2%) patient. The median time to onset was 29 days (range: 5-774 days). Six patients received systemic corticosteroids, and 5 of the 6 patients received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). One patient also received other immunosuppressants. Treatment was discontinued in 2 patients. Resolution occurred in 3 patients.
Immune-mediated hepatitis: In the combined safety database with IMFINZI monotherapy, immune-mediated hepatitis occurred in 68 (2.3%) patients, including Grade 3 in 35 (1.2%) patient, Grade 4 in 6 (0.2%) and Grade 5 (fatal) in 4 (0.1%) patient. The median time to onset was 33 days (range: 3-333 days). Forty-five of the 68 patients received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). Three patient also received mycophenolate treatment. IMFINZI was discontinued in 9 patients. Resolution occurred in 31 patients.
In the combined safety database with IMFINZI in combination with tremelimumab (n=2280), immune-mediated hepatitis occurred in 80 (3.5%) patients, including Grade 3 in 48 (2.1%) patients, Grade 4 in 8 (0.4%) patients and Grade 5 (fatal) in 2 (< 0.1%) patients. The median time to onset was 36 days (range: 1-533 days). All patients received systemic corticosteroids and 68 of the 80 patients received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). Eight patients also received other immunosuppressants. Treatment was discontinued in 27 patients. Resolution occurred in 47 patients.
In the HCC pool (n=462), immune-mediated hepatitis occurred in 34 (7.4%) patients, including Grade 3 in 20 (4.3%) patients, Grade 4 in 1 (0.2%) patient and Grade 5 (fatal) in 3 (0.6%) patients. The median time to onset was 29 days (range: 13-313 days). All patients received systemic corticosteroids, and 32 of the 34 patients received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). Nine patients also received other immunosuppressants. Treatment was discontinued in 10 patients. Resolution occurred in 13 patients.
Immune-mediated colitis: In the combined safety database with IMFINZI monotherapy, immune-mediated colitis or diarrhoea occurred in 58 (1.9%) patients, including Grade 3 in 9 (0.3%) patients and Grade 4 in 2 (<0.1%) patient. The median time to onset was 70 days (range: 1-394 days). Thirty-eight of the 58 patients received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). One patient also received infliximab treatment and 1 patient also received mycophenolate. IMFINZI was discontinued in 9 patients. Resolution occurred in 43 patients.
In the combined safety database with IMFINZI in combination with tremelimumab (n=2280), immune-mediated colitis or diarrhoea occurred in 167 (7.3%) patients, including Grade 3 in 76 (3.3%) patients and Grade 4 in 3 (0.1%) patients. The median time to onset was 57 days (range: 3-906 days). All patients received systemic corticosteroids and 151 of the 167 patients received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). Twenty-two patients also received other immunosuppressants. Treatment was discontinued in 54 patients. Resolution occurred in 141 patients.
Intestinal perforation and large intestine perforation were uncommonly reported in patients receiving IMFINZI in combination with tremelimumab.
In the HCC pool (n=462), immune-mediated colitis or diarrhoea occurred in 31 (6.7%) patients, including Grade 3 in 17 (3.7%) patients. The median time to onset was 23 days (range: 2-479 days). All patients received systemic corticosteroids, and 28 of the 31 patients received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). Four patients also received other immunosuppressants. Treatment was discontinued in 5 patients. Resolution occurred in 29 patients.
Intestinal perforation was observed in patients receiving IMFINZI in combination with tremelimumab (rare) in studies outside of the HCC pool.
Immune-mediated endocrinopathies: Immune-mediated hypothyroidism: In the combined safety database with IMFINZI monotherapy, immune-mediated hypothyroidism occurred in 245 (8.2%) patients, including Grade 3 in 4 (0.1%) patients. The median time to onset was 85 days (range: 1-562 days). Of the 245 patients, 240 patients received hormone replacement therapy and 6 patients received high-dose corticosteroids (at least 40 mg prednisone or equivalent per day) for immune-mediated hypothyroidism. No patients discontinued IMFINZI due to immune-mediated hypothyroidism.
In the combined safety database with IMFINZI in combination with tremelimumab (n=2280), immune-mediated hypothyroidism occurred in 209 (9.2%) patients, including Grade 3 in 6 (0.3%) patients. The median time to onset was 85 days (range: 1-624 days). Thirteen patients received systemic corticosteroids and 8 of the 13 received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). Treatment discontinued in 3 patients. Resolution occurred in 52 patients. Immune-mediated hypothyroidism was preceded by immune-mediated hyperthyroidism in 25 patients or immune-mediated thyroiditis in 2 patients.
In the HCC pool (n=462), immune-mediated hypothyroidism occurred in 46 (10.0%) patients. The median time to onset was 85 days (range: 26-763 days). One patient received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). All patients required other therapy including hormone replacement therapy. Resolution occurred in 6 patients. Immune-mediated hypothyroidism was preceded by immune-mediated hyperthyroidism in 4 patients.
Immune-mediated hyperthyroidism: In the combined safety database with IMFINZI monotherapy, immune-mediated hyperthyroidism occurred in 50 (1.7%) patients, there were no Grade 3 or 4 cases. The median time to onset was 43 days (range: 1-196 days). Forty-six of the 50 patients received medical therapy (thiamazole, carbimazole, propylthiouracil, perchlorate, calcium channel blocker, or beta-blocker), 11 patients received systemic corticosteroids and 4 of the 11 patients received high-dose systemic corticosteroid treatment (at least 40 mg prednisone or equivalent per day). One patient discontinued IMFINZI due to immune-mediated hyperthyroidism. Resolution occurred in 39 patients. Twenty patients experienced hypothyroidism following hyperthyroidism.
In the combined safety database with IMFINZI in combination with tremelimumab (n=2280), immune-mediated hyperthyroidism occurred in 62 (2.7%) patients, including Grade 3 in 5 (0.2%) patients. The median time to onset was 33 days (range: 4-176 days). Eighteen patients received systemic corticosteroids, and 11 of the 18 patients received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). Fifty-three patients required other therapy (thiamazole, carbimazole, propylthiouracil, perchlorate, calcium channel blocker or beta-blocker), One patient discontinued treatment due to hyperthyroidism. Resolution occurred in 47 patients.
In the HCC pool (n=462), immune-mediated hyperthyroidism occurred in 21 (4.5%) patients, including Grade 3 in 1 (0.2%) patient. The median time to onset was 30 days (range: 13-60 days). Four patients received systemic corticosteroids, and all of the four patients received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). Twenty patients required other therapy (thiamazole, carbimazole, propylthiouracil, perchlorate, calcium channel blocker, or beta-blocker). One patient discontinued treatment due to hyperthyroidism. Resolution occurred in 17 patients.
Immune-mediated thyroiditis: In the combined safety database with IMFINZI monotherapy, immune-mediated thyroiditis occurred in 12 (0.4%) patients, including Grade 3 in 2 (<0.1%) patients. The median time to onset was 49 days (range: 14-106 days). Of the 12 patients, 10 patients received hormone replacement therapy and 1 patient received high-dose corticosteroids (at least 40 mg prednisone or equivalent per day). One patient discontinued IMFINZI due to immune-mediated thyroiditis. Three patients experienced hypothyroidism following thyroiditis.
In the combined safety database with IMFINZI in combination with tremelimumab (n=2280), immune-mediated thyroiditis occurred in 15 (0.7%) patients, including Grade 3 in 1 (<0.1%) patient. The median time to onset was 57 days (range: 22-141 days). Five patients received systemic corticosteroids and 2 of the 5 patients received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). Thirteen patients required other therapy including, hormone replacement therapy, thiamazole, carbimazole, propylthiouracil, perchlorate, calcium channel blocker, or beta-blocker. No patients discontinued treatment due to immune-mediated thyroiditis. Resolution occurred in 5 patients.
In the HCC pool (n=462), immune-mediated thyroiditis occurred in 6 (1.3%) patients. The median time to onset was 56 days (range: 7-84 days). Two patients received systemic corticosteroids, and 1 of the 2 patients received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). All patients required other therapy including hormone replacement therapy. Resolution occurred in 2 patients.
Immune-mediated adrenal insufficiency: In the combined safety database with IMFINZI monotherapy, immune-mediated adrenal insufficiency occurred in 14 (0.5%) patients, including Grade 3 in 3 (<0.1%) patients. The median time to onset was 146 days (range: 20-547 days). All 14 patients received systemic corticosteroids; 4 of the 14 patients received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). No patients discontinued IMFINZI due to immune-mediated adrenal insufficiency. Resolution occurred in 3 patients.
In the combined safety database with IMFINZI in combination with tremelimumab (n=2280), immune-mediated adrenal insufficiency occurred in 33 (1.4%) patients, including Grade 3 in 16 (0.7%) patients and Grade 4 in 1 (<0.1%) patient. The median time to onset was 105 days (range: 20-428 days). Thirty-two patients received systemic corticosteroids, and 10 of the 32 patients received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). Treatment was discontinued in one patient. Resolution occurred in 11 patients.
In the HCC pool (n=462), immune-mediated adrenal insufficiency occurred in 6 (1.3%) patients, including Grade 3 in 1 (0.2%) patient. The median time to onset was 64 days (range: 43-504 days). All patients received systemic corticosteroids, and 1 of the 6 patients received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). Resolution occurred in 2 patients.
Immune-mediated type 1 diabetes mellitus: In one study with 475 locally advance, unresectable NSCLC patients, Grade-3 immune-mediated type 1 diabetes mellitus occurred in 1 (<0.1%) patient. The time to onset was 43 days. This patient recovered with sequelae, required long-term insulin therapy and IMFINZI was permanently discontinued due to immune-mediated type 1 diabetes mellitus.
In the combined safety database with IMFINZI in combination with tremelimumab (n=2280), immune-mediated type 1 diabetes mellitus occurred in 6 (0.3%) patients, including Grade 3 in 1 (<0.1%) patient and Grade 4 in 2 (<0.1%) patients. The median time to onset was 58 days (range: 7-220 days). All patients required insulin. Treatment was discontinued for 1 patient. Resolution occurred in 1 patient.
Immune-mediated hypophysitis/hypopituitarism: In the combined safety database with IMFINZI monotherapy, immune-mediated hypophysitis/hypopituitarism occurred in 2 (<0.1%) patients, both Grade 3. The time to onset for the events was 44 days and 50 days. Both patients received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day) and one patient discontinued IMFINZI due to immune-mediated hypophysitis/hypopituitarism.
In the combined safety database with IMFINZI in combination with tremelimumab (n=2280), immune-mediated hypophysitis/hypopituitarism occurred in 16 (0.7%) patients, including Grade 3 in 8 (0.4%) patients. The median time to onset for the events was 123 days (range: 63-388 days). All patients received systemic corticosteroids and 8 of the 16 patients received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). Four patients also required endocrine therapy. Treatment was discontinued in 2 patients. Resolution occurred in 7 patients.
In the HCC pool (n=462), immune-mediated hypophysitis/hypopituitarism occurred in 5 (1.1%) patients. The median time to onset for the events was 149 days (range: 27-242 days). Four patients received systemic corticosteroids, and 1 of the 4 patients received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). Three patients also required endocrine therapy. Resolution occurred in 2 patients.
Immune-mediated nephritis: In the combined safety database with IMFINZI monotherapy, immune-mediated nephritis occurred in 14 (0.5%) patients, including Grade 3 in 2 (<0.1%) patients. The median time to onset was 71 days (range: 4-393 days). Nine patients received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day) and 1 patient also received mycophenolate. IMFINZI was discontinued in 5 patients. Resolution occurred in 8 patients.
In the combined safety database with IMFINZI in combination with tremelimumab (n=2280), immune-mediated nephritis occurred in 9 (0.4%) patients, including Grade 3 in 1 (<0.1%) patient. The median time to onset was 79 days (range: 39-183 days). All patients received systemic corticosteroids and 7 patients received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). Treatment was discontinued in 3 patients. Resolution occurred in 5 patients.
In the HCC pool (n=462), immune-mediated nephritis occurred in 4 (0.9%) patients, including Grade 3 in 2 (0.4%) patients. The median time to onset was 53 days (range: 26-242 days). All patients received systemic corticosteroids, and 3 of the 4 received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). Treatment was discontinued in 2 patients. Resolution occurred in 3 patients.
Immune-mediated rash: In the combined safety database with IMFINZI monotherapy, immune-mediated rash or dermatitis occurred in 50 (1.7%) patients, including Grade 3 in 12 (0.4%) patients. The median time to onset was 43 days (range: 4-333 days). Twenty-three of the 50 patients received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). IMFINZI was discontinued in 3 patients. Resolution occurred in 32 patients.
In the combined safety database with IMFINZI in combination with tremelimumab (n=2280), immune-mediated rash or dermatitis (including pemphigoid) occurred in 112 (4.9%) patients, including Grade 3 in 17 (0.7%) patients. The median time to onset was 35 days (range: 1-778 days). All patients received systemic corticosteroids, and 57 of the 112 patients received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). Treatment was discontinued in 10 patients. Resolution occurred in 65 patients.
In the HCC pool (n=462), immune-mediated rash or dermatitis (including pemphigoid) occurred in 26 (5.6%) patients, including Grade 3 in 9 (1.9%) patients and Grade 4 in 1 (0.2%) patient. The median time to onset was 25 days (range: 2-933 days). All patients received systemic corticosteroids and 14 of the 26 patients received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). One patient received other immunosuppressants. Treatment was discontinued in 3 patients. Resolution occurred in 19 patients.
Infusion-related reactions: In the combined safety database with IMFINZI monotherapy, infusion-related reactions occurred in 49 (1.6%) patients, including Grade 3 in 5 (0.2%) patients. There were no Grade 4 or 5 events.
In the combined safety database with IMFINZI in combination with tremelimumab (n=2280), infusion-related reactions occurred in 45 (2.0%) patients, including Grade 3 in 2 (<0.1%) patients. There were no Grade 4 or 5 events.
Laboratory abnormalities: In patients treated with durvalumab monotherapy, the proportion of patients who experienced a shift from baseline to a Grade 3 or 4 laboratory abnormality was as follows: 2.4% for alanine aminotransferase increased, 3.6% for aspartate aminotransferase increased, 0.5% for blood creatinine increased, 5.7% for amylase increased and 5.6% for lipase increased. The proportion of patients who experienced a TSH shift from baseline that was ≤ULN to any grade >ULN was 18.8% and a TSH shift from baseline that was ≥LLN to any grade <LLN was 18.1%.
In patients treated with durvalumab in combination with chemotherapy, the proportion of patients who experienced a shift from baseline to a Grade 3 or 4 laboratory abnormality was as follows: 6.4% for alanine aminotransferase increased, 6.5% for aspartate aminotransferase increased, 4.2% for blood creatinine increased, 6.4% for amylase increased, and 11.7% for lipase increased. The proportion of patients who experienced a TSH shift from baseline that was ≤ULN to any grade > ULN was 20.3% and a TSH shift from baseline that was ≥LLN to any grade <LLN was 24.1%.
In patients treated with IMFINZI in combination with tremelimumab and platinum-based chemotherapy, the proportion of patients who experienced a shift from baseline to a Grade 3 or 4 laboratory abnormality was as follows: 6.2% for alanine aminotransferase increased, 5.2% for aspartate aminotransferase increased, 4.0% for blood creatinine increased, 9.4% for amylase increased and 13.6% for lipase increased. The proportion of patients who experienced a TSH shift from baseline that was ≤ULN to >ULN was 24.8% and a TSH shift from baseline that was ≥LLN to <LLN was 32.9%.
In patients treated with IMFINZI in combination with tremelimumab, the proportion of patients who experienced a shift from baseline to a Grade 3 or 4 laboratory abnormality was as follows: 5.1% for alanine aminotransferase increased, 5.8% for aspartate aminotransferase, 1.0% for blood creatinine increased, 5.9% for amylase increased and 11.3% for lipase increased. The proportion of patients who experienced a TSH shift from baseline that was ≤ULN to >ULN was 4.2% and a TSH shift from baseline that was ≥LLN to <LLN was 17.2%.
Immunogenicity: Immunogenicity of IMFINZI as monotherapy is based on pooled data in 2280 patients who were treated with IMFINZI 10 mg/kg every 2 weeks, or 20 mg/kg every 4 weeks as a single-agent and evaluable for the presence of anti-drug antibodies (ADAs). Sixty nine patients (3.0%) tested positive for treatment emergent ADAs. Neutralising antibodies (nAb) against durvalumab were detected in 0.5% (12/2280) of patients. The presence of ADAs did not have a clinically relevant effect on safety. There are insufficient number of patients to determine ADA impact on efficacy. Based on population PK analysis, slightly lower exposure are expected in ADA-positive patients however, the reduction of PK exposure is less than 30% compared to a typical patient and is not considered clinically relevant.
Across multiple phase III studies, in patients treated with IMFINZI in combination with other therapeutic agents, 0% to 10.1% of patients developed treatment-emergent ADAs. Neutralizing antibodies against durvalumab were detected in 0% to 1.7% of patients treated with IMFINZI in combination with other therapeutic agents. The presence of ADAs did not have an apparent effect on pharmacokinetics or safety.
Elderly: No overall differences in safety were reported between elderly (≥65 years) and younger patients.
In studies PACIFIC, CASPIAN and TOPAZ-1 data on safety for patients 75 years and older are too limited to draw a conclusion on this population.
In first line metastatic NSCLC patients in the POSEIDON study, some differences in safety were reported between elderly (≥65 years) and younger patients. The safety data from patients 75 years of age or older are limited to a total of 74 patients. There was a higher frequency of serious adverse reactions and discontinuation rate of any study treatment due to adverse reactions in 35 patients aged 75 years of age or older treated with IMFINZI in combination with tremelimumab and platinum-based chemotherapy (45.7% and 28.6%, respectively) relative to 39 patients aged 75 years of age or older who received platinum-based chemotherapy only (35.9% and 20.5%, respectively).
Reporting of suspected adverse reactions: Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at e-meso.pom.go.id.

Durvalumab is an immunoglobulin, therefore no formal pharmacokinetic drug-drug interaction studies have been conducted. PK drug-drug interaction between durvalumab and chemotherapy was assessed in the CASPIAN study and showed concomitant treatment with durvalumab did not impact the PK of etoposide, carboplatin or cisplatin. Additionally, based on population PK analysis, concomitant chemotherapy treatment did not meaningfully impact the PK of durvalumab. PK drug-drug interactions between durvalumab in combination with tremelimumab and platinum-based chemotherapy were assessed in the POSEIDON study and showed no clinically meaningful PK interactions between tremelimumab, durvalumab, nab-paclitaxel, gemcitabine, pemetrexed, carboplatin or cisplatin in the concomitant treatment.

Incompatibilities: Incompatibilities were either not assessed or not identified as part of registration of this medicine.

Store unopened vials under refrigeration at 2°C to 8°C in the original carton to protect from light.
Do not freeze. Do not shake.
Shelf life: 36 months.

Targeted Cancer Therapy / Cancer Immunotherapy

L01FF03 - durvalumab ; Belongs to the class of PD-1/PD-L1 (Programmed cell death protein 1/death ligand 1) inhibitors. Used in the treatment of cancer.

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