Imfinzi Special Precautions

Immune-Mediated Adverse Reactions: IMFINZI is a monoclonal antibody that belongs to a class of drugs that bind to either the programmed death-receptor 1 (PD-1) or the PD-ligand 1 (PD-L1), blocking the PD-1/PD-L1 pathway, thereby removing inhibition of the immune response, potentially breaking peripheral tolerance and inducing immune-mediated adverse reactions. Important immune-mediated adverse reactions listed under Precautions may not include all possible severe and fatal immune-mediated reactions.
The incidence and severity of immune-mediated adverse reactions were similar when IMFINZI was administered as a single agent or in combination with chemotherapy or in combination with tremelimumab and platinum-based chemotherapy, unless otherwise noted.
Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue. Immune-mediated adverse reactions can occur at any time after starting treatment with a PD-1/PD-L1 blocking antibody. While immune-mediated adverse reactions usually manifest during treatment with PD-1/PD-L1 blocking antibodies, immune-mediated adverse reactions can also manifest after discontinuation of PD-1/PD-L1 blocking antibodies.
Early identification and management of immune-mediated adverse reactions are essential to ensure safe use of PD-1/PD-L1 blocking antibodies. Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.
Withhold or permanently discontinue IMFINZI depending on severity [see Dosage & Administration]. In general, if IMFINZI requires interruption or discontinuation, administer systemic corticosteroid therapy (1 mg to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroid therapy.
Toxicity management guidelines for adverse reactions that do not necessarily require systemic steroids (e.g., endocrinopathies and dermatologic reactions) are discussed as follows.
Immune-Mediated Pneumonitis: IMFINZI can cause immune-mediated pneumonitis. The incidence of pneumonitis is higher in patients who have received prior thoracic radiation.
IMFINZI as a Single Agent: In Patients Who Did Not Receive Recent Prior Radiation: In patients who received IMFINZI on clinical trials in which radiation therapy was generally not administered immediately prior to initiation of IMFINZI, the incidence of immune-mediated pneumonitis was 2.4% (34/1414), including fatal (<0.1%), and Grade 3-4 (0.4%) adverse reactions. Events resolved in 19 of the 34 patients and resulted in permanent discontinuation in 5 patients. Systemic corticosteroids were required in 19 patients (19/34) with pneumonitis who did not receive chemoradiation prior to initiation of IMFINZI.
In Patients Who Received Recent Prior Radiation: The incidence of pneumonitis (including radiation pneumonitis) in patients with unresectable Stage III NSCLC following definitive chemoradiation within 42 days prior to initiation of IMFINZI in PACIFIC was 18.3% (87/475) in patients receiving IMFINZI and 12.8% (30/234) in patients receiving placebo. Of the patients who received IMFINZI (475) 1.1% were fatal and 2.7% were Grade 3 adverse reactions. Events resolved in 50 of the 87 patients and resulted in permanent discontinuation in 27 patients.
Systemic corticosteroids were required in 64 patients (64/87) with pneumonitis who had received chemoradiation prior to initiation of IMFINZI, while 2 patients required use of infliximab with high-dose steroids.
The frequency and severity of immune-mediated pneumonitis in patients who did not receive definitive chemoradiation prior to IMFINZI were similar whether IMFINZI was given as a single agent in patients with various cancers in a pooled data set or in patients with ES-SCLC or BTC when given in combination with chemotherapy.
IMFINZI with Tremelimumab: Immune-mediated pneumonitis occurred in 1.3% (5/388) of patients receiving IMFINZI in combination with tremelimumab, including fatal (0.3%) and Grade 3 (0.2%) adverse reactions. Events resolved in 3 of the 5 patients and resulted in permanent discontinuation in 1 patient. Systemic corticosteroids were required in all patients; of these, 4 patients required high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). One patient (1/5) required other immunosuppressants.
IMFINZI with Tremelimumab and Platinum-Based Chemotherapy: Immune-mediated pneumonitis occurred in 3.5% (21/596) of patients receiving IMFINZI in combination with tremelimumab and platinum-based chemotherapy, including fatal (0.5%), and Grade 3 (1%) adverse reactions. Events resolved in 11 of the 21 patients and resulted in permanent discontinuation in 7 patients. Systemic corticosteroids were required in all patients with immune-mediated pneumonitis, while 1 patient (1/21) required other immunosuppressants.
Immune-Mediated Colitis: IMFINZI can cause immune-mediated colitis that is frequently associated with diarrhea. Cytomegalovirus (CMV) infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies.
IMFINZI as a Single Agent: Immune-mediated colitis occurred in 2% (37/1889) of patients receiving IMFINZI, including Grade 4 (<0.1%) and Grade 3 (0.4%) adverse reactions. Events resolved in 27 of the 37 patients and resulted in permanent discontinuation in 8 patients. Systemic corticosteroids were required in all patients with immune-mediated colitis, while 2 patients (2/37) required other immunosuppressants (e.g. infliximab, mycophenolate).
IMFINZI with Tremelimumab: Immune-mediated colitis or diarrhea occurred in 6% (23/388) of patients receiving IMFINZI in combination with tremelimumab, including Grade 3 (3.6%) adverse reactions. Events resolved in 22 of the 23 patients and resulted in permanent discontinuation in 5 patients. All patients received systemic corticosteroids, and 20 of the 23 patients received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). Three patients also received other immunosuppressants.
Intestinal perforation has been observed in other studies of IMFINZI in combination with tremelimumab.
IMFINZI with Tremelimumab and Platinum-Based Chemotherapy: Immune-mediated colitis occurred in 6.5% (39/596) of patients receiving IMFINZI in combination with tremelimumab including fatal (0.2%) and Grade 3 (2.5%) adverse reactions. Events resolved in 33 of 39 patients and resulted in permanent discontinuation in 11 patients. Systemic corticosteroids were required in all patients with immune-mediated colitis, while 4 patients (4/39) required other corticosteroids.
Intestinal perforation and large intestine perforation were reported in 0.1% of patients receiving IMFINZI in combination with tremelimumab.
Immune-Mediated Hepatitis: IMFINZI can cause immune-mediated hepatitis.
IMFINZI as a Single Agent: Immune-mediated hepatitis occurred in 2.8% (52/1889) of patients receiving IMFINZI, including fatal (0.2%), Grade 4 (0.3%) and Grade 3 (1.4%) adverse reactions. Events resolved in 21 of the 52 patients and resulted in permanent discontinuation of IMFINZI in 6 patients. Systemic corticosteroids were required in all patients with immune-mediated hepatitis, while 2 patients (2/52) required use of mycophenolate with high-dose steroids.
IMFINZI with Tremelimumab: Immune-mediated hepatitis occurred in 7.5% (29/388) of patients receiving IMFINZI in combination with tremelimumab, including fatal (0.8%), Grade 4 (0.3%), and Grade 3 (4.1%) adverse reactions. Events resolved in 12 of the 29 patients and resulted in permanent discontinuation in 9 patients. Systemic corticosteroids were required in all 29 patients and all 29 patients required high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). Eight patients (8/29) required other immunosuppressants.
IMFINZI with Tremelimumab and Platinum-Based Chemotherapy: Immune-mediated hepatitis occurred in 3.9% (23/596) of patients receiving IMFINZI in combination with tremelimumab, including fatal (0.3%), Grade 4 (0.5%), and Grade 3 (2.0%) adverse reactions. Events resolved in 12 of the 23 patients and resulted in permanent discontinuation in 10 patients. Systemic corticosteroids were required in all patients with immune-mediated hepatitis, while 2 patients (2/23) required use of other immunosuppressants.
Immune-Mediated Endocrinopathies: Adrenal Insufficiency: IMFINZI can cause primary or secondary adrenal insufficiency. For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated. Withhold or permanently discontinue IMFINZI based on the severity [see Dosage & Administration].
IMFINZI as a Single Agent: Immune-mediated adrenal insufficiency occurred in 0.5% (9/1889) of patients receiving IMFINZI, including Grade 3 (<0.1%) adverse reactions. Events resolved in 1 of the 9 patients and did not lead to permanent discontinuation of IMFINZI in any patients. Systemic corticosteroids were required in all patients with adrenal insufficiency; of these, the majority remained on systemic corticosteroids.
IMFINZI with Tremelimumab: Immune-mediated adrenal insufficiency occurred in 1.5% (6/388) of patients receiving IMFINZI in combination with tremelimumab, including Grade 3 (0.3%) adverse reactions. Events resolved in 2 of the 6 patients. Systemic corticosteroids were required in all 6 patients, and of these, 1 patient required high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day).
IMFINZI with Tremelimumab and Platinum-Based Chemotherapy: Immune-mediated adrenal insufficiency occurred in 2.2% (13/596) of patients receiving IMFINZI in combination with tremelimumab, including Grade 3 (0.8%) adverse reactions. Events resolved in 2 of the 13 patients and resulted in permanent discontinuation in 1 patient. Systemic corticosteroids were required in all patients with adrenal insufficiency. One patient also required endocrine therapy.
Hypophysitis: IMFINZI can cause immune-mediated hypophysitis. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field cuts. Hypophysitis can cause hypopituitarism. Initiate symptomatic treatment including hormone replacement as clinically indicated. Withhold or permanently discontinue IMFINZI depending on severity [see Dosage & Administration].
IMFINZI as a Single Agent: Grade 3 hypophysitis/hypopituitarism occurred in <0.1% (1/1889) of patients who received IMFINZI. Treatment with systemic corticosteroids was administered in this patient. The event did not lead to permanent discontinuation of IMFINZI.
IMFINZI with Tremelimumab: Immune-mediated hypophysitis/hypopituitarism occurred in 1% (4/388) of patients receiving IMFINZI in combination with tremelimumab. Events resolved in 2 of the 4 patients. Systemic corticosteroids were required in 3 patients, and of these, 1 patient received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). Two patients also required endocrine therapy.
IMFINZI with Tremelimumab and Platinum-Based Chemotherapy: Immune-mediated hypophysitis occurred in 1.3% (8/596) of patients receiving IMFINZI in combination with tremelimumab, including Grade 3 (0.5%) adverse reactions. Events resulted in permanent discontinuation in 1 patient. Systemic corticosteroids were required in 6 patients with immune-mediated hypophysitis; of these, 2 of the 8 patients received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). Four patients also required endocrine therapy.
Thyroid Disorders: IMFINZI can cause immune-mediated thyroid disorders. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism. Initiate hormone replacement therapy for hypothyroidism or institute medical management of hyperthyroidism as clinically indicated. Withhold or discontinue IMFINZI based on the severity [see Dosage & Administration].
Thyroiditis: IMFINZI as a Single Agent: Immune-mediated thyroiditis occurred in 0.5% (9/1889) of patients receiving IMFINZI, including Grade 3 (<0.1%) adverse reactions. Events resolved in 4 of the 9 patients and resulted in permanent discontinuation in 1 patient. Systemic corticosteroids were required in 3 patients (3/9) with immune-mediated thyroiditis, while 8 patients (8/9) required endocrine therapy.
IMFINZI with Tremelimumab: Immune-mediated thyroiditis occurred in 1.5% (6/388) of patients receiving IMFINZI in combination with tremelimumab. Events resolved in 2 of the 6 patients. Systemic corticosteroids were required in 2 patients (2/6) with immune-mediated thyroiditis; of these, 1 patient required high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). All patients required other therapy including hormone replacement therapy, thiamazole, carbimazole, propylthiouracil, perchlorate, calcium channel blocker, or beta-blocker.
IMFINZI with Tremelimumab and Platinum-Based Chemotherapy: Immune-mediated thyroiditis occurred in 1.2% (7/596) of patients receiving IMFINZI in combination with tremelimumab. Events resolved in 2 of the 7 patients and one resulted in permanent discontinuation. Systemic corticosteroids were required in 2 patients (2/7) with immune-mediated thyroiditis, while all patients required endocrine therapy.
Hyperthyroidism: IMFINZI as a Single Agent: Immune-mediated hyperthyroidism occurred in 2.1% (39/1889) of patients receiving IMFINZI. Events resolved in 30 of the 39 patients and did not lead to permanent discontinuation of IMFINZI in any patients. Systemic corticosteroids were required in 9 patients (9/39) with immune-mediated hyperthyroidism, while 35 patients (35/39) required endocrine therapy.
IMFINZI with Tremelimumab: Immune-mediated hyperthyroidism occurred in 4.6% (18/388) of patients receiving IMFINZI in combination with tremelimumab, including Grade 3 (0.3%) adverse reactions. Events resolved in 15 of the 18 patients. Two patients (2/18) required high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). Seventeen patients required other therapy (thiamazole, carbimazole, propylthiouracil, perchlorate, calcium channel blocker, or beta-blocker).
IMFINZI with Tremelimumab and Platinum-Based Chemotherapy: Immune-mediated hyperthyroidism occurred in 5% (30/596) of patients receiving IMFINZI in combination with tremelimumab, including Grade 3 (0.2%) adverse reactions. Events resolved in 21 of the 30 patients. Systemic corticosteroids were required in 5 patients (5/30) with immune-mediated hyperthyroidism, while 28 patients (28/30) required endocrine therapy.
Hypothyroidism: IMFINZI as a Single Agent: Immune-mediated hypothyroidism occurred in 8.3% (156/1889) of patients receiving IMFINZI, including Grade 3 (<0.1%) adverse reactions. Events resolved in 31 of the 156 patients and did not lead to permanent discontinuation of IMFINZI in any patients. Systemic corticosteroids were required in 11 patients (11/156) and the majority of patients (152/156) required long-term thyroid hormone replacement.
IMFINZI with Tremelimumab: Immune-mediated hypothyroidism occurred in 11% (42/388) of patients receiving IMFINZI in combination with tremelimumab. Events resolved in 5 of the 42 patients. One patient received high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). All patients required other therapy (thiamazole, carbimazole, propylthiouracil, perchlorate, calcium channel blocker, or beta-blocker).
IMFINZI with Tremelimumab and Platinum-Based Chemotherapy: Immune-mediated hypothyroidism occurred in 8.6% (51/596) of patients receiving IMFINZI in combination with tremelimumab, including Grade 3 (0.5%) adverse reactions. Systemic corticosteroids were required in 2 patients (2/51) and all patients required endocrine therapy.
IMFINZI with Carboplatin and Paclitaxel: Immune-mediated hypothyroidism occurred in 14% (34/235) of patients receiving IMFINZI in combination with carboplatin and paclitaxel. Events resolved in 8 of the 34 patients. Endocrine therapy was required in 34 of the 34 patients.
Type 1 Diabetes Mellitus, which can present with diabetic ketoacidosis: Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Initiate treatment with insulin as clinically indicated. Withhold or permanently discontinue IMFINZI based on the severity [see Dosage & Administration].
IMFINZI as a Single Agent: Grade 3 immune-mediated type 1 diabetes mellitus occurred in <0.1% (1/1889) of patients receiving IMFINZI. This patient required long-term insulin therapy and IMFINZI was permanently discontinued. Two additional patients (0.1%, 2/1889) had events of hyperglycemia requiring insulin therapy that did not resolve at the time of reporting.
IMFINZI with Tremelimumab: Two patients (0.5%, 2/388) had events of hyperglycemia requiring insulin therapy that had not resolved at last follow-up.
IMFINZI with Tremelimumab and Platinum-Based Chemotherapy: Immune-mediated Type 1 diabetes mellitus occurred in 0.5% (3/596) of patients receiving IMFINZI in combination with tremelimumab, including Grade 3 (0.3%) adverse reactions. All patients required endocrine therapy.
Immune-Mediated Nephritis with Renal Dysfunction: IMFINZI can cause immune-mediated nephritis.
IMFINZI as a Single Agent: Immune-mediated nephritis occurred in 0.5% (10/1889) of patients receiving IMFINZI, including Grade 3 (<0.1%) adverse reactions. Events resolved in 5 of the 10 patients and resulted in permanent discontinuation in 3 patients. Systemic corticosteroids were required in all patients with immune-mediated nephritis.
IMFINZI with Tremelimumab: Immune-mediated nephritis occurred in 1% (4/388) of patients receiving IMFINZI in combination with tremelimumab, including Grade 3 (0.5%) adverse reactions. Events resolved in 3 of the 4 patients and resulted in permanent discontinuation in 2 patients. Systemic corticosteroids were required in all patients with immune-mediated nephritis; of these, 3 patients required high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day).
IMFINZI with Tremelimumab and Platinum-Based Chemotherapy: Immune-mediated nephritis occurred in 0.7% (4/596) of patients receiving IMFINZI in combination with tremelimumab, including Grade 3 (0.2%) adverse reactions. Events resolved in 1 of the 4 patients and resulted in permanent discontinuation in 3 patients. Systemic corticosteroids were required in all patients with immune-mediated nephritis.
Immune-Mediated Dermatology Reactions: IMFINZI can cause immune-mediated rash or dermatitis (including pemphigoid), defined as requiring use of systemic corticosteroids and with no clear alternate etiology. Exfoliative dermatitis, including Stevens Johnson Syndrome (SJS), drug rash with eosinophilia and systemic symptoms (DRESS), and toxic epidermal necrolysis (TEN), has occurred with PD-1/L-1 blocking antibodies. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-exfoliative rashes. Withhold or permanently discontinue IMFINZI depending on severity [see Dosage & Administration].
IMFINZI as a Single Agent: Immune-mediated rash or dermatitis (including pemphigoid) occurred in 1.8% (34/1889) of patients receiving IMFINZI, including Grade 3 (0.4%) adverse reactions. Events resolved in 19 of the 34 patients and resulted in permanent discontinuation in 2 patients. Systemic corticosteroids were required in all patients with immune-mediated rash or dermatitis.
IMFINZI with Tremelimumab: Immune-mediated rash or dermatitis occurred in 4.9% (19/388) of patients receiving IMFINZI in combination with tremelimumab, including Grade 4 (0.3%) and Grade 3 (1.5%) adverse reactions. Events resolved in 13 of the 19 patients and resulted in permanent discontinuation in 2 patients. Systemic corticosteroids were required in all patients with immune-mediated rash or dermatitis; of these, 12 patients required high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day). One patient received other immunosuppressants.
IMFINZI with Tremelimumab and Platinum-Based Chemotherapy: Immune-mediated rash or dermatitis occurred in 7.2% (43/596) of patients receiving IMFINZI in combination with tremelimumab, including Grade 3 (0.3%) adverse reactions. Events resolved in 32 of the 43 patients and resulted in permanent discontinuation in 2 patients. Systemic corticosteroids were required in all patients with immune-mediated rash or dermatitis.
Immune-Mediated Pancreatitis: IMFINZI in combination with tremelimumab can cause immune-mediated pancreatitis.
IMFINZI with Tremelimumab: Immune-mediated pancreatitis occurred in 2.3% (9/388) of patients receiving IMFINZI in combination with tremelimumab, including Grade 4 (0.3%) and Grade 3 (1.5%) adverse reactions. Events resolved in 6 of the 9 patients. Systemic corticosteroids were required in all 9 patients and of these 7 patients required high-dose corticosteroid treatment (at least 40 mg prednisone or equivalent per day).
Other Immune-Mediated Adverse Reactions: The following clinically significant, immune-mediated adverse reactions occurred at an incidence of less than 1% each in patients who received IMFINZI or IMFINZI in combination with tremelimumab, or were reported with the use of other PD-1/PD-L1 blocking antibodies.
Cardiac/vascular: Myocarditis, pericarditis, vasculitis.
Nervous system: Meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barré syndrome, nerve paresis, autoimmune neuropathy.
Ocular: Uveitis, iritis, and other ocular inflammatory toxicities can occur. Some cases can be associated with retinal detachment. Various grades of visual impairment to include blindness can occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome, as this may require treatment with systemic steroids to reduce the risk of permanent vision loss.
Gastrointestinal: Pancreatitis including increases in serum amylase and lipase levels, gastritis, duodenitis.
Musculoskeletal and connective tissue disorders: Myositis/polymyositis, rhabdomyolysis and associated sequelae including renal failure, arthritis, polymyalgia rheumatic.
Endocrine: Hypoparathyroidism.
Other (hematologic/immune): Hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenia, solid organ transplant rejection, other transplant (including corneal graft) rejection.
Infusion-Related Reactions: IMFINZI can cause severe or life-threatening infusion-related reactions.
Monitor for signs and symptoms of infusion-related reactions. Interrupt, slow the rate of, or permanently discontinue IMFINZI based on the severity [see Dosage & Administration]. For Grade 1 or 2 infusion-related reactions, consider using pre-medications with subsequent doses.
IMFINZI as a Single Agent: Infusion-related reactions occurred in 2.2% (42/1889) of patients receiving IMFINZI, including Grade 3 (0.3%) adverse reactions.
IMFINZI in Combination with Tremelimumab: Infusion-related reactions occurred in 2.6% (10/388) of patients receiving IMFINZI in combination with tremelimumab.
IMFINZI with Tremelimumab and Platinum-Based Chemotherapy: Infusion-related reactions occurred in 2.9% (17/596) of patients receiving IMFINZI in combination with tremelimumab, including Grade 3 (0.3%) adverse reactions.
Complications of Allogeneic HSCT after IMFINZI: Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with a PD-1/L-1 blocking antibody. Transplant-related complications include hyperacute graft-versus-host-disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease (VOD) after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause). These complications may occur despite intervening therapy between PD-1/L-1 blockade and allogeneic HSCT.
Follow patients closely for evidence of transplant-related complications and intervene promptly. Consider the benefit versus risks of treatment with a PD-1/L-1 blocking antibody prior to or after an allogeneic HSCT.
Embryo-Fetal Toxicity: Based on its mechanism of action and data from animal studies, IMFINZI can cause fetal harm when administered to a pregnant woman. In animal reproduction studies, administration of durvalumab to cynomolgus monkeys from the onset of organogenesis through delivery resulted in increased premature delivery, fetal loss and premature neonatal death. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with IMFINZI and for 3 months after the last dose of IMFINZI [see Use in Pregnancy & Lactation].
Use in Children: The safety and effectiveness of IMFINZI have not been established in pediatric patients. Safety and efficacy were assessed but not established in a multi-center, open-label study (NCT03837899) in 45 pediatric patients aged 1 to < 17 years with advanced solid tumors. All 45 patients received at least a single dose of IMFINZI, and 41 patients received IMFINZI in combination with tremelimumab. No new safety signals were observed in pediatric patients in this study.
Durvalumab systemic exposure in pediatric patients weighing ≥ 35 kg was within the range of values previously observed in adults given the same weight-based dose, whereas the systemic exposure in pediatric patients weighing < 35 kg was lower than that observed in adults.
Use in the Elderly: Of the 401 patients with resectable NSCLC treated with IMFINZI in combination with chemotherapy in the AEGEAN study, 209 (52%) patients were 65 years or older and 49 (12%) patients were 75 years or older. There were no overall clinically meaningful differences in safety or efficacy between patients ≥ 65 years of age and younger patients.
Of the 476 patients with unresectable, Stage III NSCLC treated with IMFINZI in the PACIFIC study, 45% were 65 years or older, while 7.6% were 75 years or older. No overall differences in safety or effectiveness were observed between patients 65 years or older and younger patients. The PACIFIC study did not include sufficient numbers of patients aged 75 years and over to determine whether they respond differently from younger patients.
Of the 330 patients with metastatic NSCLC treated with IMFINZI in combination with tremelimumab and platinum-based chemotherapy, 143 (43%) patients were 65 years or older and 35 (11%) patients were 75 years or older. There were no clinically meaningful differences in safety or efficacy between patients 65 years or older and younger patients.
Of the 265 patients with ES-SCLC treated with IMFINZI in combination with chemotherapy, 101 (38%) patients were 65 years or older and 19 (7.2%) patients were 75 years or older. There were no clinically meaningful differences in safety or efficacy between patients 65 years or older and younger patients.
Of the 338 patients with BTC treated with IMFINZI in combination with chemotherapy in the TOPAZ-1 study, 158 (47%) patients were 65 years or older and 38 (11%) patients were 75 years or older. No overall differences in safety or effectiveness of IMFINZI have been observed between patients 65 years of age and older and younger adult patients.
Of the 393 patients with uHCC treated with IMFINZI in combination with tremelimumab, 50% of patients were 65 years of age or older and 13% of patients were 75 years of age or older. No overall differences in safety or effectiveness of IMFINZI have been observed between patients 65 years of age and older and younger adult patients.
Of the 235 patients with endometrial cancer treated with IMFINZI with carboplatin and paclitaxel, 49% of patients were 65 years of age or older and 12% of patients were 75 years of age or older. No overall differences in safety or effectiveness of IMFINZI have been observed between patients 65 years of age and older and younger adult patients.