EU’s CHMP Recommends Approving Perioperative Nivolumab Combo in NSCLC

The FDA approved perioperative nivolumab plus chemotherapy for patients with resectable EGFR-mutated or ALK-rearranged NSCLC in October 2024 based on data from the CheckMate 77T trial.

The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended the approval of neoadjuvant nivolumab (Opdivo) plus chemotherapy in combination with adjuvant nivolumab after surgery for patients with PD-L1–positive resectable non–small cell lung cancer (NSCLC) at a high risk of recurrence in the EU, according to a press release from the developer, Bristol Myers Squibb.¹

The European Commission will now review the CHMP’s opinion on approving the nivolumab-based regimen for this NSCLC population. If approved, the perioperative nivolumab combination would be the second nivolumab-containing regimen to be commercially available for managing resectable NSCLC in the EU.

“Preventing disease recurrence and improving long-term outcomes for patients with NSCLC earlier in the treatment journey is critical to addressing unmet needs and is one of our top priorities,” Dana Walker, MD, MSCE, vice president, nivolumab global program lead, Bristol Myers Squibb, stated in the press release.¹ “With today's positive opinion from the CHMP, we are pleased that our second [nivolumab]-based regimen for certain patients with resectable NSCLC whose tumors have PD-L1 expression [of 1% or higher] is one step closer to being approved in the [EU].”

The CHMP based its recommendation on findings from the phase 3 CheckMate 77T trial (NCT04025879), which evaluated the perioperative nivolumab combination therapy vs neoadjuvant placebo plus chemotherapy followed by adjuvant placebo among 461 patients with resectable stage IIA to IIIB NSCLC. Investigators presented findings from CheckMate 77T at the 2023 European Society of Medical Oncology Congress and subsequently published them in The New England Journal of Medicine.²

After a median follow-up of 25.4 months, published findings showed an 18-month event-free survival (EFS) rate of 70.2% in the nivolumab arm vs 50.0% in the placebo arm per blinded independent review (HR, 0.58; 97.36% CI, 0.42-0.81; P <.001).Investigator assessment also revealed an EFS benefit with the nivolumab combination (HR, 0.56; 95% CI, 0.41-0.76).

At the time of analysis, pathological complete responses (pCRs) occurred in 25.3% (95% CI, 19.8%-31.5%) of the nivolumab arm vs 4.7% (95% CI, 2.4%-8.3%) in the placebo arm (OR, 6.64; 95% CI, 3.40-12.97). Additionally, major pathological responses were highlighted in 35.4% (95% CI, 29.2%-41.9%) and 12.1% (95% CI, 8.2%-17.0%) of each arm (OR, 4.01; 95% CI, 2.48-6.49).

Adverse effects (AEs) occurred in 97.4% of the nivolumab arm compared with 97.8% of the placebo arm. Additionally, grade 3/4 treatment-related toxicities affected 32.5% and 25.2% of patients in each respective arm. The most common grade 3/4 AE in the nivolumab and placebo arms, respectively, was decreased neutrophil counts (10.1% vs 6.5%).

“I am extremely encouraged by the findings of CheckMate 77T evaluating neoadjuvant nivolumab and chemotherapy followed by surgery and adjuvant nivolumab, and by how continuing adjuvant nivolumab after surgery may further improve outcomes and provide a potentially more durable benefit for our patients,” Tina Cascone, MD, PhD, associate professor of Thoracic/Head and Neck Medical Oncology at The University of Texas MD Anderson Cancer Center, stated in a prior press release on findings from CheckMate 77T.³ “The results from the CheckMate 77T study are promising for physicians, patients and their families alike.”

In the double-blind CheckMate 77T trial, patients were randomly assigned 1:1 to receive nivolumab or placebo plus chemotherapy in the neoadjuvant setting followed by nivolumab or placebo in the adjuvant setting. Neoadjuvant therapy included nivolumab at 360 mg or matched placebo plus platinum-doublet chemotherapy every 3 weeks for 4 cycles. Adjuvant therapy, which began 90 days after surgery, consisted of nivolumab at 480 mg or matched placebo every 4 weeks for 1 year.

The trial’s primary end point was EFS based on blinded independent review. Secondary end points included pCR, major pathological response, overall survival, and safety.

The FDA approved perioperative nivolumab plus chemotherapy for patients with resectable EGFR-mutated or ALK-rearranged NSCLC in October 2024 based on data from the CheckMate 77T trial.⁴

References

1. Bristol Myers Squibb receives positive CHMP opinion for perioperative regimen of neoadjuvant Opdivo® (nivolumab) and chemotherapy followed by surgery and adjuvant Opdivo for resectable non-small cell lung cancer in patients with tumor cell PD-L1... News release. Bristol Myers Squibb. March 28, 2025. Accessed March 31, 2025. https://tinyurl.com/4x66z54r
2. Cascone T, Awad MM, Spicer JD, et al. Perioperative nivolumab in resectable lung cancer. N Engl J Med. 2024;390(19):1756-1769. doi:10.1056/NEJMoa2311926
3. 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 March 31, 2025. https://tinyurl.com/jj9yxahd
4. FDA approves neoadjuvant/adjuvant nivolumab for resectable non-small cell lung cancer. News release. FDA. October 3, 2024. Accessed March 31, 2025. https://tinyurl.com/bdfcps54