Imfinzi

In combination w/ platinum-containing chemotherapy (as neoadjuvant treatment) followed by Imfinzi as a single agent (as adjuvant treatment after surgery) for the treatment of adults w/ resectable (tumors ≥4 cm &/or node +ve) NSCLC & no known epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements (NSCLC). As a single agent for the treatment of adults w/ unresectable stage III NSCLC whose disease has not progressed following concurrent platinum-based chemotherapy & RT (NSCLC). In combination w/ tremelimumab & platinum-based chemotherapy for the treatment of adults w/ metastatic NSCLC w/ no sensitizing EGFR mutations or ALK genomic tumor aberrations (NSCLC). In combination w/ etoposide & either carboplatin or cisplatin for the 1st-line treatment of adults w/ extensive-stage small cell lung cancer (ES-SCLC). In combination w/ gemcitabine & cisplatin for the treatment of adults w/ locally advanced or metastatic biliary tract cancer (BTC). In combination w/ tremelimumab for the treatment of adults w/ unresectable hepatocellular carcinoma (uHCC). In combination w/ carboplatin & paclitaxel followed by Imfinzi as a single agent for the treatment of adults w/ primary advanced or recurrent endometrial cancer that is mismatch repair deficient (dMMR).

Administer as IV infusion over 60 min. Resectable NSCLC Administer Imfinzi prior to chemotherapy. Duration of therapy: Until disease progression that precludes definitive surgery, recurrence, unacceptable toxicity, or max of 12 cycles after surgery. Patient weighing ≥30 kg Neoadjuvant: 1,500 mg in combination w/ chemotherapy every 3 wk for up to 4 cycles prior to surgery. Adjuvant: 1,500 mg as single agent every 4 wk for up to 12 cycles after surgery. Patient weighing <30 kg Neoadjuvant: 20 mg/kg every 3 wk in combination w/ chemotherapy for up to 4 cycles prior to surgery. Adjuvant: 20 mg/kg every 4 wk for up to 12 cycles as single agent after surgery. Unresectable stage III NSCLC Duration of therapy: Until disease progression, unacceptable toxicity, or max of 12 mth. Patient weighing ≥30 kg 10 mg/kg every 2 wk or 1,500 mg every 4 wk. Patient weighing <30 kg 10 mg/kg every 2 wk. ES-SCLC Duration of therapy: Until disease progression or unacceptable toxicity. Patient weighing ≥30 kg 1,500 mg in combination w/ chemotherapy every 3 wk (21 days) for 4 cycles, followed by 1,500 mg every 4 wk as single agent. Patient weighing <30 kg 20 mg/kg in combination w/ chemotherapy every 3 wk (21 days) for 4 cycles, followed by 20 mg/kg every 4 wk as single agent. BTC Duration of therapy: Until disease progression or unacceptable toxicity. Patient weighing ≥30 kg 1,500 mg in combination w/ chemotherapy every 3 wk (21 days) up to 8 cycles, followed by 1,500 mg every 4 wk as single agent. Patient weighing <30 kg 20 mg/kg in combination w/ chemotherapy every 3 wk (21 days) up to 8 cycles, followed by 20 mg/kg every 4 wk as single agent. uHCC Administer tremelimumab prior to Imfinzi on the same day. Duration of therapy: After cycle 1 of combination therapy, administer Imfinzi as a single agent every 4 wk until disease progression or unacceptable toxicity. Patient weighing ≥30 kg 1,500 mg following a single dose of tremelimumab 300 mg on day 1 of cycle 1; continue 1,500 mg as single agent every 4 wk. Patient weighing <30 kg 20 mg/kg following a single dose of tremelimumab 4 mg/kg on day 1 of cycle 1; continue 20 mg/kg as single agent every 4 wk. dMMR endometrial cancer Duration of therapy: Until disease progression or unacceptable toxicity. Patient weighing ≥30 kg 1,120 mg in combination w/ carboplatin & paclitaxel every 3 wk (21 days) for 6 cycles, followed by 1,500 mg every 4 wk as single agent. Patient weighing <30 kg 15 mg/kg in combination w/ carboplatin & paclitaxel every 3 wk (21 days) for 6 cycles, followed by 20 mg/kg every 4 wk as single agent. Metastatic NSCLC Continue Imfinzi until disease progression or intolerable toxicity. Dosing interval change from every 3 wk to every 4 wk starting at cycle 5. If patients receive fewer than 4 cycles of platinum-based chemotherapy, the remaining cycles of tremelimumab (up to a total of 5) should be given after the platinum-based chemotherapy phase, in combination w/ Imfinzi, every 4 wk. Patient weighing ≥30 kg Tremelimumab 75 mg, followed by Imfinzi 1,500 mg, then carboplatin & nab-paclitaxel (or carboplatin or cisplatin & pemetrexed for non-squamous disease; or carboplatin or cisplatin & gemcitabine for squamous disease). Patient weighing <30 kg Tremelimumab 1 mg/kg, followed by Imfinzi 20 mg/kg, then carboplatin & nab-paclitaxel (or carboplatin or cisplatin & pemetrexed for non-squamous disease; or carboplatin or cisplatin & gemcitabine for squamous disease).

Risk of immune-mediated adverse reactions. Evaluate liver enzymes, creatinine, & thyroid function at baseline & periodically during treatment. W/hold treatment for severe (grade 3) immune-mediated adverse reactions. Permanently discontinue treatment for life-threatening (grade 4) or recurrent severe (grade 3) immune-mediated adverse reactions. Risk of infusion-related reactions. Interrupt infusion or slow infusion rate for grade 1 or 2 infusion-related reactions. Permanently discontinue infusion for grade 3 or 4 infusion-related reactions. Fatal & other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation before or after being treated w/ a PD-1/L-1 blocking Ab. Can cause fetal harm when administered to a pregnant woman. Females of reproductive potential should use effective contraception during treatment & for 3 mth after the last dose. Women should not breastfeed during treatment & for 3 mth after the last dose. Safety & effectiveness have not been established in ped patients.

Most common (≥20%) in resectable stage II/III NSCLC: Anemia, nausea, constipation, fatigue, musculoskeletal pain, rash. Most common (≥20%) in unresectable stage III NSCLC: Cough, fatigue, pneumonitis/radiation pneumonitis, URTIs, dyspnea, rash. Most common (≥20%) in metastatic NSCLC: Nausea, fatigue, musculoskeletal pain, decreased appetite, rash, diarrhea. Most common (≥20%) in ES-SCLC: Nausea, fatigue/asthenia, alopecia. Most common (≥20%) in BTC: Fatigue, nausea, constipation, decreased appetite, abdominal pain, rash, pyrexia. Most common (≥20%) in uHCC: Rash, diarrhea, fatigue, pruritus, musculoskeletal pain, abdominal pain. Most common (≥20%) in advanced or recurrent dMMR endometrial cancer: Peripheral neuropathy, musculoskeletal pain, nausea, alopecia, fatigue, abdominal pain, constipation, rash, decreased Mg, increased ALT/AST, diarrhea, vomiting, cough, decreased K, dyspnea, headache, increased alkaline phosphatase, decreased appetite.

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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