Opdivo Fails to Extend Survival in SCLC Patients in Phase 3 Trial, Bristol-Myers Squibbs Reports

Opdivo Fails to Extend Survival in SCLC Patients in Phase 3 Trial, Bristol-Myers Squibbs Reports

Bristol-Myers Squibb‘s immune checkpoint inhibitor Opdivo (nivolumab) is no better than standard chemotherapy at extending the lives of patients with small cell lung cancer (SCLC) who failed prior platinum-based chemotherapy, a Phase 3 trial shows.

Although Opdivo’s safety profile was consistent to that reported in previous clinical studies involving SCLC patients, the Phase 3 CheckMate-331 trial (NCT02481830) did not meet its primary objective of overall survival, Bristol-Myers Squibbs reports.

“Small cell lung cancer is a highly aggressive disease in which significant unmet need remains,” Sabine Maier, MD, development lead, thoracic cancers at Bristol-Myers Squibb, said in a press release. “We are focused on researching innovative oncology therapies to improve outcomes for patients with lung cancer. We thank the patients, their families, and the physicians involved in the CheckMate-331 study.”

SCLC patients who relapse after an initial response to their first-line platinum-based chemotherapy are usually given chemotherapy with topotecan. In Japan, amrubicin is approved as a second-line SCLC treatment and may also be offered.

The problem with chemotherapies is that they act on growing and dividing cells, regardless of being cancerous or normal. Damage to healthy cells causes side effects, including a dampened immune system, loss of hair, and gastrointestinal tract problems.

Opdivo is an immune checkpoint inhibitor meant to block signals from cancer cells that prevent immune cells from recognizing and eliminating them effectively. The approach is approved for many cancers, and had shown promise in a Phase 1/2 trial in SCLC patients.

This study, called CheckMate-032 (NCT01928394), included 401 previously treated patients with SCLC. Response rates were 11% with Opdivo alone, and 22% with a combination of Opdivo and Yervoy (ipilimumab).

These results led the U.S. Food and Drug Administration to grant accelerated approval to Opdivo as a treatment for patients with metastatic SCLC who have failed platinum-based chemotherapy and at least one other line of treatment.

An accelerated approval is usually granted based on overall response rates and duration of responses, but is dependent on confirmation of the treatment’s safety and effectiveness in additional trials.

For this purpose, the company launched the Phase 3 CheckMate-331 trial, which was aimed at determining if Opdivo was better then standard chemotherapy at extending the lives of patients who had failed prior platinum-based chemotherapy, with or without radiation therapy.

It included approximately 300 patients across 149 clinical centers worldwide — including Japan — who randomly received Opdivo or standard chemotherapy — topotecan or amrubicin.

In addition to its primary goal of extending survival, which was not met, researchers also aimed to determine the time a patient lived until their disease worsened and the number of patients responding to treatment as secondary measures.

Bristol-Myers is now investigating the role of Opdivo, alone or in combination with Yervoy, as a maintenance therapy for SCLC patients who achieved at least stable disease after first-line chemotherapy.

In another Phase 2 trial (NCT03670056) for SCLC, which is not yet recruiting participants, researchers will study how Opdivo impacts tumor-infiltrating immune cell populations and its correlation with clinical response.