Imfinzi (durvalumab) for muscle-invasive bladder cancer

Initial US Approval:

2017

Key Clinical Studies:

NIAGARA (NCT03732677)

Drug Class/Description:

Programmed death-ligand 1 (PD-L1) blocking antibody

Indications and Usage:

Imfinzi is a programmed death-ligand 1 (PD-L1) blocking antibody indicated:

• in combination with platinum-containing chemotherapy as neoadjuvant treatment, followed by IMFINZI continued as a single agent as adjuvant treatment after surgery, for the treatment of adult patients with resectable (tumors ≥ 4 cm and/or node positive) non-small cell lung cancer (NSCLC) and no known epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements.
• as a single agent, for the treatment of adult patients with unresectable, Stage III NSCLC whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy.
• in combination with tremelimumab-actl and platinum-based chemotherapy, for the treatment of adult patients with metastatic NSCLC with no sensitizing EGFR mutations or ALK genomic tumor aberrations.
• as a single agent, for the treatment of adult patients with limited-stage small cell lung cancer (LS-SCLC) whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy.
• in combination with etoposide and either carboplatin or cisplatin, as first-line treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC).
• in combination with gemcitabine and cisplatin, as treatment of adult patients with locally advanced or metastatic biliary tract cancer (BTC).
• in combination with tremelimumab-actl, for the treatment of adult patients with unresectable hepatocellular carcinoma (uHCC).
• in combination with carboplatin and paclitaxel followed by IMFINZI as a single agent, for the treatment of adult patients with primary advanced or recurrent endometrial cancer that is mismatch repair deficient (dMMR) as determined by an FDA-approved test.
• in combination with gemcitabine and cisplatin as neoadjuvant treatment, followed by single agent IMFINZI as adjuvant treatment following radical cystectomy, for the treatment of adult patients with muscle invasive bladder cancer (MIBC). 

Dosage and Administration:

• Administer IMFINZI as an intravenous infusion over 60 minutes after dilution. 
• Neoadjuvant and Adjuvant Treatment of Resectable NSCLC:
  • Weight ≥ 30 kg:
    • Neoadjuvant: IMFINZI 1,500 mg in combination with chemotherapy every 3 weeks for up to 4 cycles prior to surgery.
    • Adjuvant: IMFINZI 1,500 mg as a single agent every 4 weeks for up to 12 cycles after surgery.
  • Weight < 30 kg:
    • Neoadjuvant: IMFINZI 20 mg/kg every 3 weeks in combination with chemotherapy for up to 4 cycles prior to surgery.
    • Adjuvant: 20 mg/kg every 4 weeks as a single agent for up to 12 cycles after surgery. 
• Unresectable Stage III NSCLC, following concurrent platinum-based chemotherapy and radiation therapy: 
  • Weight ≥ 30 kg: IMFINZI 10 mg/kg every 2 weeks or 1,500 mg every 4 weeks.
  • Weight < 30 kg: IMFINZI 10 mg/kg every 2 weeks.
• Metastatic NSCLC:
  • Weight ≥ 30 kg: IMFINZI 1,500 mg every 3 weeks in combination with tremelimumab-actl 75 mg and platinum-based chemotherapy for 4 cycles, and then administer IMFINZI 1,500 mg every 4 weeks as a single agent with histology-based pemetrexed maintenance therapy every 4 weeks, and a fifth dose of tremelimumab-actl 75 mg in combination with IMFINZI dose 6 at week 16.
  • Weight < 30 kg: IMFINZI 20 mg/kg every 3 weeks in combination with tremelimumab-actl 1 mg/kg and platinum-based chemotherapy, and then administer IMFINZI 20 mg/kg every 4 weeks as a single agent with histology-based pemetrexed therapy every 4 weeks, and a fifth dose of tremelimumab-actl 1 mg/kg in combination with IMFINZI dose 6 at week 16.
• LS-SCLC, following concurrent platinum-based chemotherapy and radiation therapy:
  • Weight ≥ 30 kg: 1,500 mg every 4 weeks. 
  • Weight < 30 kg: 20 mg/kg every 4 weeks.
• ES-SCLC:
  • Weight ≥ 30 kg: With etoposide and either carboplatin or cisplatin, administer IMFINZI 1,500 mg every 3 weeks in combination with chemotherapy, and then 1,500 mg every 4 weeks as a single agent. 
  • Weight < 30 kg: With etoposide and either carboplatin or cisplatin, administer IMFINZI 20 mg/kg every 3 weeks in combination with chemotherapy, and then 10 mg/kg every 2 weeks as a single agent.
• BTC:
  • Weight ≥ 30 kg: administer IMFINZI 1,500 mg every 3 weeks in combination with chemotherapy, and then 1,500 mg every 4 weeks as a single agent.
  • Weight < 30 kg: administer IMFINZI 20 mg/kg every 3 weeks in combination with chemotherapy, and then 20 mg/kg every 4 weeks as a single agent.
• uHCC:
  • Weight ≥ 30 kg: IMFINZI 1,500 mg in combination with tremelimumab-actl 300 mg as a single dose at Cycle 1/Day 1, followed by IMFINZI as a single agent every 4 weeks.
  • Weight < 30 kg: IMFINZI 20 mg/kg in combination with tremelimumab-actl 4 mg/kg as a single dose at Cycle 1/Day 1, followed by IMFINZI as a single agent every 4 weeks.
• dMMR endometrial cancer:
  • Weight ≥ 30 kg: IMFINZI 1,120 mg in combination with carboplatin and paclitaxel every 3 weeks for 6 cycles, followed by IMFINZI 1,500 mg every 4 weeks as a single agent.
  • Weight < 30 kg: IMFINZI 15 mg/kg in combination with carboplatin and paclitaxel every 3 weeks for 6 cycles, followed by IMFINZI 20 mg/kg every 4 weeks as a single agent.
• MIBC:
  • Weight ≥ 30 kg:  
    • Neoadjuvant: IMFINZI 1,500 mg in combination with gemcitabine and cisplatin every 3 weeks for 4 cycles prior to surgery.
    • Adjuvant: IMFINZI 1,500 mg every 4 weeks as a single agent for up to 8 cycles after surgery. 
  • Weight < 30 kg:  
    • Neoadjuvant: IMFINZI 20 mg/kg in combination with gemcitabine and cisplatin every 3 weeks for 4 cycles prior to surgery. 
    • Adjuvant: IMFINZI 20 mg/kg every 4 weeks as a single agent for up to 8 cycles after surgery. 
• See full Prescribing Information for preparation and administration instructions and dosage modifications for adverse reactions. 

Dosage Forms and Strengths:

• Injection: 500 mg/10 mL (50 mg/mL) solution in a single-dose vial.
• Injection: 120 mg/2.4 mL (50 mg/mL) solution in a single-dose vial.

Contraindications:

None.

Warnings and Precautions:

• Immune-Mediated Adverse Reactions
  • Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue, including the following: immune-mediated pneumonitis, immune-mediated colitis, immune-mediated hepatitis, immune-mediated endocrinopathies, immune-mediated dermatologic adverse reactions, immunemediated nephritis and renal dysfunction, solid organ transplant rejection, and immune-mediated pancreatitis.
  • Monitor for early identification and management. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment.
  • Withhold or permanently discontinue based on severity and type of reaction.
• Infusion-Related Reactions: Interrupt, slow the rate of infusion, or permanently discontinue IMFINZI based on the severity of the reaction. 
• Complications of Allogeneic HSCT: Fatal and other serious complications can occur in patients who receive allogeneic HSCT before or after being treated with a PD-1/PD-L1 blocking antibody.
• Embryo-Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and use of effective contraception. 

Adverse Reactions:

IMFINZI in Combination with Chemotherapy

• Most common adverse reactions (≥ 20%) of patients with resectable, Stage II/III NSCLC [neoadjuvant /adjuvant]) are anemia, nausea, constipation, fatigue, musculoskeletal pain, and rash.

IMFINZI as a Single Agent

• Most common adverse reactions (≥ 20%) of patients with unresectable, Stage III NSCLC) are cough, fatigue, pneumonitis/radiation pneumonitis, upper respiratory tract infections, dyspnea, and rash.

IMFINZI in Combination with Tremelimumab-actl and Platinum-Based Chemotherapy

• Most common adverse reactions (≥ 20%) of patients with metastatic NSCLC) are nausea, fatigue, musculoskeletal pain, decreased appetite, rash, and diarrhea.

IMFINZI as a Single Agent

• Most common adverse reactions (≥ 20%) of patients with limited-stage SCLC) are pneumonitis or radiation pneumonitis, and fatigue.

IMFINZI in Combination with Platinum-Based Chemotherapy

• Most common adverse reactions (≥ 20%) of patients with extensive-stage SCLC) are nausea, fatigue/asthenia, and alopecia.

IMFINZI in Combination with Gemcitabine and Cisplatin

• Most common adverse reactions (≥ 20%) of patients with BTC) are fatigue, nausea, constipation, decreased appetite, abdominal pain, rash, and pyrexia.

IMFINZI in Combination with Tremelimumab-actl

• Most common adverse reactions (≥ 20%) of patients with uHCC) are rash, diarrhea, fatigue, pruritus, musculoskeletal pain, and abdominal pain.

IMFINZI in Combination with Carboplatin and Paclitaxel, followed by IMFINZI as a single agent

• Most common adverse reactions (≥ 20%) of patients with endometrial cancer) were peripheral neuropathy, musculoskeletal pain, nausea, alopecia, fatigue, abdominal pain, constipation, rash, decreased magnesium, increased ALT, increased AST, diarrhea, vomiting, cough, decreased potassium, dyspnea, headache, and increased alkaline phosphatase.

IMFINZI in Combination with Gemcitabine and Cisplatin, followed by IMFINZI as a single agent

• Most common adverse reactions (≥ 20% of patients with MIBC) were decreased hemoglobin, decreased neutrophils, increased blood creatinine, decreased sodium, nausea, increased ALT, decreased calcium, decreased platelets, fatigue, increased potassium, decreased lymphocytes, increased AST, constipation, decreased magnesium, decreased appetite, increased alkaline phosphate, rash, pyrexia, diarrhea, vomiting and abdominal pain. 

Use in Specific Populations:

• Lactation: Advise not to breastfeed.

Adapted From:

https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/761069s000lbl.pdf

 

Every health-care provider should make their own determination regarding specific safe and appropriate patient care practices, including drug dosages and indications. The provider should always consult the most recent prescribing/product information. FDA Focus information is not guaranteed to be accurate, complete, or current. JADPRO and its editors, authors, reviewers, and commentators cannot be held responsible for any liability incurred as a consequence of the application of any of the information listed within.