FDA Accepts sBLA for Immunotherapy Combo in Non-Small Cell Lung Cancer

Officials with the FDA have accepted Bristol-Myers Squibb’s supplemental biologics license application (sBLA) for nivolumab (Opdivo) plus low-dose ipilimumab (Yervoy) for the treatment of first-line advanced non-small cell lung cancer (NSCLC), according to a press release.

The application is based on positive results from the CheckMate-227 phase 3 clinical trial evaluating the nivolumab plus ipilimumab regimen versus chemotherapy in first-line NSCLC patients with tumor mutational burden (TMB) ≥10 mutations per megabase (mut/Mb). Nivolumab is dosed at 3 mg/kg every 2 weeks with low-dose ipilimumab (1 mg/kg) every 6 weeks.

In part 1 of the trial, the 2 co-primary endpoints are overall survival in patients whose tumors express PD-L1 and progression-free survival (PFS) in patients with TMB ≥10 mut/Mb across the PD-L1 spectrum.

The trial includes:

• Part 1a: Nivolumab plus low-dose ipilimumab or nivolumab monotherapy versus chemotherapy in patients whose tumors express PD-L1.
• Part 1b: Nivolumab plus low-dose iplimumab or nivolumab plus chemotherapy versus chemotherapy in patients whose tumors do not express PD-L1.
• Part 2: Nivolumab plus chemotherapy versus chemotherapy, regardless of PD-L1 or TMB status.

According to the data, the PFS benefit was observed regardless of PD-L1 expression levels and in both squamous and non-squamous tumor histology. The 1-year PFS rate was 42.6% with the combination treatment compared with 13.2% with chemotherapy, and the median PFS was 7.2 months. The objective response rate was 45.3% versus 26.9% with chemotherapy.

In an early descriptive analysis, encouraging overall survival benefits were observed with the combination versus chemotherapy in patients with TMB ≥10 mut/Mb.

“Lung cancer is a complex disease, and we believe multiple treatment approaches, including those that are biomarker-driven, are needed to help individual patients,” Sabine Maier, MD, development lead of thoracic cancers at Bristol-Myers Squibb, said in the press release. “We look forward to working with the FDA throughout the review process to bring this important treatment option to patients.”

The target FDA action date for the combination treatment is February 20, 2019.

Reference

1. U.S. Food and Drug Administration (FDA) Accepts Application for Opdivo Plus Low-Dose Yervoy for Treatment of First-Line Non-Small Cell Lung Cancer in Patients with Tumor Mutational Burden ≥10 mut/Mb [news release]. Bristol-Myers Squibb. https://news.bms.com/press-release/corporatefinancial-news/us-food-and-drug-administration-fda-accepts-application-opdivo. Accessed June 21, 2018.

2. Hellmann MD, Ciuleanu TE, Pluzanski A, et al. Nivolumab plus ipilimumab in lung cancer with high tumor mutational burden. NEJM. 2018. Doi: 10.1056/NEJMoa1801946