FDA, EMA Accept Applications for Nivolumab Combo in Resectable NSCLC

The application submitted to the FDA is a supplemental biologics license application (sBLA) and has been assigned a Prescription Drug User Fee Act date of October 8, 2024.

Both the FDA and the European Medicines Agency (EMA) have accepted regulatory applications for the neoadjuvant combination of nivolumab (Opdivo) and chemotherapy followed by surgery and adjuvant nivolumab as a perioperative treatment for patients with stage IIA to IIIB non–small cell lung cancer (NSCLC), according to a press release from Bristol Myers Squibb, the developer of nivolumab.¹

The application submitted to the FDA is a supplemental biologics license application (sBLA) and has been assigned a Prescription Drug User Fee Act date of October 8, 2024.

The EMA had validated a type II variation application in late January 2024 for the combination; therefore, the regulatory agency’s centralized review process has begun.

Both applications were supported with findings from the phase 3 CheckMate-77T trial (NCT04025879), which demonstrated statistically significant and clinically meaningful improvements in event-free survival (EFS) as per blinded independent central review (BICR) with the neoadjuvant/adjuvant nivolumab/chemotherapy regimen compared with neoadjuvant chemotherapy and placebo followed by surgery and adjuvant placebo in this patient population.² The results were presented during the 2023 European Society of Medical Oncology (ESMO) Congress.³

At a median follow-up of 25.4 months, the nivolumab regimen led to a 42% reduction in the risk of disease recurrence, progression, or death compared with the chemotherapy approach (HR, 0.58; 97.36% CI, 0.42-0.81; P = .00025). Additionally, the pathologic complete response (pCR) rate was 25.3% vs. 4.7%, respectively; the major pathologic response (MPR) rate was 35.4% vs 12.1%, respectively.

The study remains ongoing to assess overall survival (OS).

"Between 30% to 55% of [patients with NSCLC] who undergo surgery will experience disease recurrence. We are working to expand options that improve outcomes for patients with resectable disease, as part of our comprehensive approach to the treatment of multiple types of cancer, including and especially in earlier stages,” Abderrahim Oukessou, MD, vice president, thoracic cancers global program lead, Bristol Myers Squibb, stated in a press release.¹

“With CheckMate-77T, we have evaluated the potential for neoadjuvant immunotherapy to induce [pCR] and the role of perioperative [nivolumab] treatment in reducing the likelihood that the cancer will return and help make extended survival possible for patients,” Oukessou added. “The acceptance of these applications underscores our impactful progress in addressing unmet needs across several [NSCLC] cancer treatment settings and brings us one step closer to offering a new perioperative [nivolumab]-based regimen to patients who may benefit."

In the phase 3, double-blind, placebo-controlled, multicenter CheckMate-77T trial, investigators randomly assigned 452 patients with resectable stage IIA to IIIB NSCLC to receive neoadjuvant nivolumab with chemotherapy followed by surgery and adjuvant nivolumab vs neoadjuvant chemotherapy and placebo followed by surgery. In the nivolumab arm, patients received 360 mg of nivolumab every 3 weeks plus chemotherapy every 3 weeks for 4 cycles followed by surgery within 6 weeks of neoadjuvant therapy, and 480 mg of nivolumab every 4 weeks for 1 year. In the comparator arm, patients received placebo/chemotherapy every 3 weeks for 4 cycles followed by surgery within 6 weeks of neoadjuvant therapy, followed by placebo for 1 year.

Eligibility criteria included having stage IIA to IIIB NSCLC, no prior systemic therapy, and no EGFR mutations or known ALK alterations. Stratification factors included disease histology, disease stage, and PD-L1 status.

The primary end point is EFS, and secondary endpoints include OS, pCR, and MPR.

Additional results showed that the definitive surgery rates were 78% with the nivolumab-based regimen compared with 77% with chemotherapy and placebo, with complete resection rates at 89% and 90% of patients, respectively.

Furthermore, data showed that the safety profile of the regimen was consistent with previously reported studies, and no new safety signals were identified. All-grade surgery-related adverse effects (AEs) occurred in 41% of patients on the nivolumab arm compared with 39% of those on the placebo arm; 12% of patients in each arm had grade 3/4 AEs. There were 2 treatment-related deaths in the nivolumab arm due to grade 5 pneumonitis and grade 4 pneumonitis (n = 1 each). Both occurred after completion of the neoadjuvant treatment.

References

1. Bristol Myers Squibb announces acceptance of U.S. and EU regulatory filings for neoadjuvant Opdivo (nivolumab) and chemotherapy followed by surgery and adjuvant Opdivo in resectable non-small cell lung cancer. News release. Bristol Myers Squibb. February 7, 2023. Accessed February 7, 2023. https://news.bms.com/news/corporate-financial/2024/Bristol-Myers-Squibb-Announces-Acceptance-of-U.S.-and-EU-Regulatory-Filings-for-Neoadjuvant-Opdivo-nivolumab-and-Chemotherapy-Followed-by-Surgery-and-Adjuvant-Opdivo-in-Resectable-Non-Small-Cell-Lung-Cancer/default.aspx
2. Perioperative regimen of neoadjuvant Opdivo (nivolumab) and chemotherapy followed by adjuvant opdivo shows significant improvement in event-free survival for patients with resectable non-small cell lung cancer in phase 3 CheckMate-77T trial. News release. Bristol Myers Squibb. October 17, 2023. Accessed February 7, 2023. https://news.bms.com/news/corporate-financial/2023/Perioperative-Regimen-of-Neoadjuvant-Opdivo-nivolumab-and-Chemotherapy-Followed-by-Adjuvant-Opdivo-Shows-Significant-Improvement-in-Event-Free-Survival-for-Patients-with-Resectable-Non-Small-Cell-Lung-Cancer-in-Phase-3-CheckMate--77T-Trial/default.aspx
3. Cascone T, Awad MM, Spicer JD, et al. CheckMate 77T: phase III study comparing neoadjuvant nivolumab (NIVO) plus chemotherapy (chemo) vs neoadjuvant placebo plus chemo followed by surgery and adjuvant NIVO or placebo for previously untreated, resectable stage II–IIIB NSCLC. Ann Oncol. 2023;34(suppl 2):S1295. doi:10.1016/j.annonc.2023.10.050