Approval Status: Initially approved May 2017
Specific Treatments: advanced or metastatic urothelial carcinoma and Stage III non-small cell lung cancer
Imfinzi (durvalumab) is a programmed death-ligand 1 (PD-L1) blocking antibody.
Imfinzi is specifically indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who:
1) have disease progression during or following platinum-containing chemotherapy
2) have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy
Imfinzi is also specifically approved 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.
Imfinzi is supplied as an infusion for intravenous administration. The recommended dose is 10 mg/kg administered as an intravenous infusion over 60 minutes every 2 weeks until disease progression or unacceptable toxicity. Please see drug label for treatment modifications.
This indication was approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. The accelerated FDA approval of Imfinzi was based on the urothelial cancer cohort of a multicenter, multicohort, open-label clinical trial. This cohort consisted of 182 patients with locally advanced or metastatic urothelial carcinoma who had progressed while on or after a platinum-based therapy, including those who progressed within 12 months of receiving therapy in a neo-adjuvant or adjuvant setting. These patients had initiated durvalumab therapy at least 13 weeks prior to the data cut-off date. All patients received Imfinzi 10 mg/kg via intravenous infusion every 2 weeks for up to 12 months or until unacceptable toxicity or disease progression. Tumor assessments were performed at Weeks 6, 12 and 16, then every 8 weeks for the first year and every 12 weeks thereafter. The major efficacy outcome measures were confirmed Objective Response Rate (ORR) according to RECIST v1.1 as assessed by Blinded Independent Central Review (BICR), and duration of response (DoR). The ORR was 17% and the median DoR was not reached. Among the total 31 responding patients, 1s (45%) had ongoing responses of 6 months or longer and five (16%) had ongoing responses of 12 months or longer.
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.
Adverse effects associated with the use of Imfinzi may include, but are not limited to, the following:
- musculoskeletal pain
- decreased appetite
- peripheral edema
- urinary tract infection
Adverse effects associated with the use of Imfinzi for non-small cell lung cancer (NSCLC) include :
- upper respiratory tract infections
- shortness of breath
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.
For additional information regarding Imfinzi or advanced or metastatic urothelial carcinoma and non-small cell lung cancer, please visit https://www.imfinzi.com/