FDA Grants Priority Review to BLA for First-Line Nivolumab/Ipilimumab Plus Limited Chemo in NSCLC

The FDA has accepted the Biologics License Application (BLA) for and granted Priority Review to the combination of nivolumab (Opdivo) plus ipilimumab (Yervoy) with limited chemotherapy as a first-line treatment of patients with metastatic or recurrent non—small cell lung cancer (NSCLC) who have noEGFRor ALKgenomic tumor aberrations, according to a press release from Bristol Myers Squibb (BMS). The Prescription Drug Free User Act target action date is set as August 6, 2020, and the combination was granted Fast Track designation.¹

An application for the combination was subsequently validated by the European Medicines Agency (EMA).

“Despite treatment advances, there remains a serious unmet need for additional innovative treatment options for lung cancer patients globally,” said Sabine Maier, MD, development lead, thoracic cancers, Bristol Myers Squibb, in a statement. “The FDA’s acceptance and EMA’s validation of our applications represent important milestones for patients with lung cancer, and we look forward to working with regulatory authorities to bring the first and only dual immunotherapy plus limited chemotherapy regimen to patients as soon as possible.

The submission of the BLA to the FDA was supported by data from the phase III CheckMate-9LA trial (NCT03215706), which met its primary end point of overall survival (OS) back in October 2019, at which time BMS stated that the results would be presented at an upcoming medical congress.²

The CheckMate-9LA trial is open and actively recruiting patients. The open-label, multicenter, randomized trial to evaluate the use of nivolumab, ipilimumab, and chemotherapy as a first-line treatment for patients with advanced NSCLC, regardless of PD-L1 expression status. The target enrollment for the study is 700 participants who must have histologically confirmed stage IV or recurrent NSCLC, squamous or non-squamous histology, with no prior systemic anticancer therapy, an ECOG performance status ≤1, and measurable disease.

As treatment, patients in the experimental arm receive 360 mg nivolumab every 3 weeks plus 1 mg/kg ipilimumab every 6 weeks and 2 cycles of chemotherapy, which consists of carboplatin, paclitaxel, pemetrexed, and cisplatin. In the comparator arm, patients receive up to 4 cycles of chemotherapy followed by maintenance therapy with pemetrexed, given they meet the eligibility requirements for chemotherapy.

The key secondary end points of the study include progression-free survival (PFS) and overall response rate (ORR) in the intention-to-treat population as well as PFS, OS, and ORR by PD-L1 expression and tumor mutational burden status.

The combination of nivolumab and ipilimumab is being explored in ongoing studies across multiple malignancies. Of note in lung cancer,results from the phase III CheckMate-227 trial led to an FDA Priority Review for nivolumab/ipilimumabin advanced NSCLC earlier this year. The study evaluated the combination versus chemotherapy.

The median OS achieved with nivolumab/ipilimumab was 17.2 months versus 14.9 months.

In patients who received chemotherapy (HR, 0.79; 97.72% CI, 0.65-0.96;P= .007). In addition, the objective response rate (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. These arms were favorable over the chemotherapy arm which demonstrated an ORR of 30% with CRs in 1.8% of patients and PRs in 28.2% of patients.

References

1. Bristol Myers Squibb announces acceptance of U.S. and EU regulatory filings for Opdivo (nivolumab) plus Yervoy (ipilimumab) combined with limited chemotherapy in first-line lung cancer [news release]. Princeton, New Jersey: Bristol Myers Squibb; April 8, 2020. https://bit.ly/39VpR40. Accessed April 8, 2020.
2. CheckMate-9LA, a phase 3 trial evaluating Opdivo (nivolumab) plus low-dose Yervoy (ipilimumab) combined with chemotherapy, meets primary endpoint demonstrating superior overall survival compared to chemotherapy alone in first-line lung cancer [news release]. Princeton, New Jersey: Bristol Myers Squibb; October 22, 2019. https://bit.ly/3bZUJ4W. Accessed April 8, 2020.