FDA Priority Review Granted To Nivolumab/Ipilimumab for Treatment of Advanced NSCLC

The FDA has granted priority review to the Biologics License Application for nivolumab (Opdivo) in combination with ipilimumab (Yervoy) for the first-line treatment of patients with metastatic or recurrent non-small cell lung cancer (NSCLC) with noEGFRorALKgenomic tumor aberrations, according to a press release from the Bristol-Myers Squibb Company.¹

The BLA was submitted based on data frompart 1 of the phase III CheckMate-227 trial, which evaluated the combination versus chemotherapy in patients with previously untreated NSCLC. The data presented at the Society for Immunotherapy of Cancer (SITC) Annual Meeting showed that nivolumab plus ipilimumab resulted in a median overall survival (OS) of 17.2 months versus 14.9 months in patients with tumor PD-L1 expression ≥1% who were given chemotherapy (HR, 0.79; 97.72% CI, 0.65-0.96;P= .007). Nivolumab/ipilimumab showed an overall survival of 40% compared with 33% in patients who were given chemotherapy.²

For patients with PD-L1 expression ≥50%, the OS was also favorable in the immunotherapy combination arm compared with chemotherapy and a third arm in which patients received nivolumab alone. The median OS was 21.2 months for the nivolumab/ipilimumab arm, 18.1 months for the nivolumab-only arm, and 14.0 months for the chemotherapy arm. The median duration of response (DOR) in these arms was 31.8, 17.5, and 5.8 months, respectively.

The overall response rate (ORR) for patients in the patients who received nivolumab plus ipilimumab was also favorable compared with the monotherapy and chemotherapy arms. Specifically, the ORR in the immunotherapy arm was 35.0%, which included complete responses (CRs) in 5.8% of patients, and partial responses (PRs) in 30.1% of patients. In the nivolumab arm, the ORR was 27.5% including CRs in 3% of patients and PRs in 24.5% of patients. Finally, the chemotherapy arm had a 30% ORR with CRs in 1.8% of patients and PRs in 28.2% of patients.

In terms of safety, treatment-related adverse events (TRAEs) occurred less frequently in the immunotherapy arm than the others. The immunotherapy combination led to a higher amount of treatment discontinuation than the other treatment arms, though. Overall, the rate of discontinuation for patients in the immunotherapy arm was 18% versus 12% in the nivolumab monotherapy arm, and 9% in the chemotherapy arm.

“The FDA’s acceptance of our application for Opdivo plus Yervoy represents an important milestone for patients with lung cancer in the United States, where, despite recent treatment advances, lung cancer remains the cause of more than 150,000 deaths each year,” said Sabine Maier, MD, development lead, thoracic cancers, Bristol-Myers Squibb. “Lung cancer is the third tumor type where the combination of Opdivo and Yervoy has demonstrated a significant long-term overall survival benefit in a randomized phase 3 trial, which further validates the immunologic rationale for dual Immuno-Oncology therapy.”

CheckMate-227 is an ongoing open-label randomized trial. The co-primary end points of the study are OS and progression-free survival. The secondary end points are ORR and disease-related symptom improvement as measured by the Lung Cancer Symptom Score. The study includes patients with stage IV or recurrent NSCLC who have an ECOG performance status ≤1, measurable disease, and no prior systemic anti-cancer therapy. Individuals with untreated metastases are ineligible to enroll.

The Priority Review for nivolumab plus ipilimumab for the first-line treatment of patients with metastatic or recurrent NSCLC has a Prescription Drug User Fee Act goal date of May 15, 2020.

References

1. US Food and Drug Administration accepts for priority review Bristol-Myers Squibb’s application for opdivo (nivolumab) plus yervoy (ipilimumab) in first-line non-small cell lung cancer [news release]. Princeton, New Jersey: Bristol-Myers Squibb; January 15, 2020.https://bit.ly/3acD89H. Accessed January 15, 2020.
2. Brahmer JR. Point-counterpoint: new data and controversies on immunotherapy combinations in the first-line treatment of NSCLC. Presented at: 34th Annual Meeting & Pre-Conference Programs of the Society for Immunotherapy of Cancer (SITC 2019). November 7-10, 2019. National Harbor, MD.