FDA Issues CRL for Lilly’s Sintilimab for First-Line NSCLC

The FDA has issued a complete response letter (CRL) for the biologics license application for sintilimab injection, a PD-1 inhibitor in combination with pemetrexed and platinum chemotherapy for the first-line treatment of people with nonsquamous non-small cell lung cancer (NSCLC).

The CRL includes a recommendation for an additional clinical study, specifically a multiregional clinical trial comparing standard of care therapy for first line metastatic NSCLC to sintilimab with chemotherapy utilizing a non-inferiority design with an overall survival endpoint.

This regulatory decision is consistent with the outcome of the Oncologic Drugs Advisory Committee Meeting in February. The ODAC had voted 14-1 vote in support for additional testing for sintilimab. In a statement after the meeting, Eli Lilly, one of the drugs developers, said it had hoped that its aggressive pricing strategy for the therapy would have swayed the committee.

But the agency does not take costs or pricing strategy into account when making decisions. Both the agency and the committee had objected to the reliance of studies only done in China. The agency cited in materials ahead of the meeting that multiregional trials are the preferred approach according to guidelines from the International Council for Harmonization and that most drug applications in the United States are based on multiregional trials. ORIENT-11, the trial used for this application, was conducted in China only, and regulators indicated the patients enrolled didn’t reflect the U.S. population. Patients in the study were young, predominantly male, with lower rates of smoking, and didn’t represent racial and ethnic minorities.

The FDA also indicated that if consulted ahead of the application, it would have advised company of the need for a trial with overall survival as an endpoint. In the ORIENT-11 trial, progression-free survival was the primary endpoint, with overall response rate and duration f response as secondary endpoints.

Sintilimab is an investigational PD-1 inhibitor developed by Innovent Biologics and Lilly. Sintilimab is a type of immunoglobulin G4 monoclonal antibody, which binds to PD-1 molecules on the surface of T-cells, blocks the PD-1 / PD-Ligand 1 (PD-L1) pathway, and reactivates T-cells to kill cancer cells.

Innovent is currently conducting more than 20 clinical studies of sintilimab to evaluate its safety and efficacy in a wide variety of cancer indications, including more than 10 registrational or pivotal clinical trials.