Imfinzi (durvalumab) - 2 indications

Scroll down for additional information on each indication:

• for adults with unresectable stage III non-small cell lung cancer; approved February 2018
• as first-line treatment of adults with extensive-stage small cell lung cancer; approved March of 2020

General Information

Imfinzi (durvalumab) is a programmed death-ligand 1 (PD-L1) blocking antibody.

Imfinzi is specifically indicated for the following:

• for patients with Stage III non-small cell lung cancer whose tumor cannot be removed by surgery (unresectable) and whose disease has not progressed following platinum-based chemotherapy given at the same time as radiation therapy. 
• as a 1st-line treatment for adult patients with extensive-stage small cell lung cancer in combination with standard-of-care chemotherapies, etoposide and either carboplatin or cisplatin (platinum-etoposide).

Imfinzi was previously granted accelerated approval for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. However, this approval was withdrawn in February of 2021 following a failure to meet endpoints in the phase 3 post-approval DANUBE clinical study.

Imfinzi is supplied as an infusion for intravenous administration. Scroll down for recommended dosing/administration for each indication.

Mechanism of Action

Imfinzi (durvalumab) is a programmed death-ligand 1 (PD-L1) blocking antibody. Expression of PD-L1 can be induced by inflammatory signals (e.g., IFN-gamma) and can be expressed on both tumor cells and tumor-associated immune cells in the tumor microenvironment. PD-L1 blocks T-cell function and activation through interaction with PD-1 and CD80. By binding to its receptors, PD-L1 reduces cytotoxic T-cell activity, proliferation, and cytokine production. Durvalumab is a human immunoglobulin G1 kappa (IgG1κ) monoclonal antibody that blocks the interaction of PD-L1 with PD-1 and CD80. Blockade of PD-L1/PD-1 and PD-L1/CD80 interactions releases the inhibition of immune responses, without inducing antibody dependent cell mediated cytotoxicity.

Side Effects

Adverse effects associated with the use of Imfinzi in patients with unresectable, Stage III NSCLC) may include, but are not limited to, the following:

• cough
• fatigue
• pneumonitis/radiation pneumonitis
• upper respiratory tract infections
• dyspnea
• rash

Adverse effects associated with the use of Imfinzi in patients with extensive-stage SCLC) may include, but are not limited to, the following:

• nausea
• fatigue/asthenia
• alopecia

Indication 1 - adults with unresectable stage III non-small cell lung cancer

approved February 2018

Dosing/Administration

• Patients with a body weight of 30 kg and more: 10 mg/kg every 2 weeks or 1500 mg every 4 weeks
• Patients with a body weight of less than 30 kg: 10 mg/kg every 2 week

Treat until disease progression, unacceptable toxicity, or a maximum of 12 months

Clinical Trial Results

The FDA approval of Imfinzi for non-small cell lung cancer was based on the PACIFIC study in 713 patients with unresectable Stage 3 NSCLC who completed at least 2 cycles of concurrent platinum-based chemotherapy and radiation before starting study drug. Imfinzi was tested against placebo. The endpoints were progression free survival and overall survival. The median time for PFS was 16.8 months for 476 patients receiving Imfinzi compared with 5.6 months for 237 patients receiving placebo. Subjects in the Imfinzi arm had a 48% lower chance of lung cancer growing or spreading than those receiving placebo.

Indication 2  - first-line treatment of adults with extensive-stage small cell lung cancer

approved March of 2020

Dosing/Administration

• Patients with a body weight of 30 kg and more: 1500 mg in combination with chemotherapy1 every 3 weeks (21 days) for 4 cycles, followed by 1500 mg every 4 weeks as a single agent
• Patients with a body weight of less than 30 kg: 20 mg/kg in combination with chemotherapy every 3 weeks (21 days) for 4 cycles, followed by 10 mg/kg every 2 weeks as a single agent

Treat until disease progression or unacceptable toxicity

Clinical Trial Results

The FDA approval of Imfinzi for 1st-line treatment for adult patients with extensive-stage small cell lung cancer in combination with standard-of-care chemotherapies, etoposide and either carboplatin or cisplatin (platinum-etoposide) was based on the phase 3 CASPIAN trial. The trial used a fixed dose of Imfinzi(1500 mg) administered every three weeks for four cycles while in combination with chemotherapy and then every four weeks until disease progression as a single medicine. The trial had two primary endpoints comparing experimental arms to SoC. In the Imfinzi plus SoC arm, the risk of death was reduced by 27%, with median OS of 13.0 months versus 10.3 months for SoC alone. Results also showed an increased confirmed objective response rate in the Imfinzi plus SoC arm (68% versus 58% for SoC alone).