CHMP Offers Positive Opinion for Perioperative Nivolumab Plus Chemo in Resectable PD-L1+ NSCLC

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The European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has recommended the approval of nivolumab (Opdivo) in combination with platinum-based chemotherapy as neoadjuvant treatment, followed by nivolumab as monotherapy as adjuvant treatment after surgical resection, for adult patients with resectable non–small cell lung cancer (NSCLC) at high risk of recurrence whose tumors have a PD-L1 expression level of at least 1%.1

The positive opinion was supported by data from the phase 3 CheckMate 77T trial (NCT04025879), which showed that patients with stage II to IIIB NSCLC treated with perioperative nivolumab plus chemotherapy (n = 229) experienced a median event-free survival (EFS) that was not reached (NR; 95% CI, 28.9-NR) per blinded independent central review (BICR) compared with 18.4 months (95% CI, 13.6-28.1) in those given a perioperative placebo plus neoadjuvant chemotherapy (n = 232; HR, 0.58; 95% CI, 0.42-0.81; P = .00025).2 The EFS benefit was similar per investigator assessment (HR, 0.56; 95% CI, 0.41-0.76).

“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 and the Opdivo global program lead at Bristol Myers Squibb, stated in a news 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 [at least] 1%, is one step closer to being approved in the European Union.”

In October 2024, the FDA approved nivolumab (Opdivo) with platinum-doublet chemotherapy as neoadjuvant treatment, followed by single-agent nivolumab after surgery as adjuvant treatment, for adults with resectable (tumors ≥ 4 cm and/or node positive) NSCLC without known EGFR mutations or ALK rearrangements.3 This regulatory decision was also supported by findings from CheckMate 77T.

CheckMate 77T Deep Dive

The global, double-blind, placebo-controlled study enrolled patients with resectable stage IIA (> 4 cm) to IIIB (N2) NSCLC absent of EGFR mutations or ALK alterations.2 No prior systemic therapy was permitted, and patients needed to have an ECOG performance status of 0 to 1.

Patients were randomly assigned in a 1:1 fashion; in the experimental arm, patients received nivolumab at 360 mg once every 3 weeks plus chemotherapy once every 3 weeks for 4 total cycles as neoadjuvant therapy, followed by 480 mg of nivolumab once every 4 weeks for up to 1 years following surgery. In the placebo arm, patients received 4 cycles of neoadjuvant placebo plus chemotherapy, followed by adjuvant placebo once every 4 weeks for up to 1 year. In both arms, neoadjuvant chemotherapy regimens included cisplatin plus pemetrexed, carboplatin plus pemetrexed, or carboplatin plus paclitaxel for patients with nonsquamous histology; or cisplatin plus docetaxel or carboplatin plus paclitaxel for those with squamous histology.

Stratification factors included histology (squamous vs nonsquamous), disease stage (II vs III), and PD-L1 status (≥ 1% vs < 1% vs not evaluable/indeterminate).

BICR-assessed EFS served as the trial’s primary end point. Secondary end points included pathological complete response (pCR) rate, major pathological response (MPR) rate, overall survival (OS), and safety.

Additional data presented at the 2023 ESMO Congress showed that the median EFS was NR for patients with stage II disease treated in the nivolumab arm (n = 81) and in the placebo arm (n = 81; HR, 0.81; 95% CI, 0.46-1.43). In those with stage III disease, the median EFS was 30.2 months (95% CI, 26.9-NR) for the nivolumab regimen (n = 148) vs 13.4 months (95% CI, 9.8-17.7) for the placebo regimen (n = 149; HR, 0.51; 95% CI, 0.6-0.72).

The nivolumab regimen was also associated with improved EFS outcomes in patients with a PD-L1 expression of at least 1% (HR, 0.52; 95% CI, 0.35-0.78) compared with those who had a PD-L1 expression of less than 1% (HR, 0.73; 95% CI, 0.47-1.15).

In the nivolumab arm, the pCR and MPR rates were 25.3% and 35.4%, respectively. These respective rates were 4.7% (odds ratio [OR], 6.64; 95% CI, 3.40-12.97) and 12.1% (OR, 4.01; 95% CI, 2.48-6.49) in the placebo arm.

Assessment of OS data is ongoing.1

Overall safety data between the neoadjuvant and adjuvant treatment periods showed that any-grade adverse effects (AEs) occurred in 97% of patients in the nivolumab arm vs 98% of patients in the placebo arm.2 The rates of grade 3/4 AEs were 47% and 43%, respectively. Treatment-related AEs (TRAEs) of any grade were reported in 89% of patients in the nivolumab arm vs 87% of patients in the placebo arm. The respective rates of grade 3/4 TRAEs were 32% and 25%.

Any-grade TRAEs led to treatment discontinuation in 19% of patients in the nivolumab arm vs 7% of patients in the placebo arm. Grade 3/4 TRAEs leading to treatment discontinuation occurred at rates of 11% and 5%, respectively.

Any-grade serious AEs were reported in 42% (treatment-related, 19%) of patients in the nivolumab arm vs 31% (treatment-related, 10%) of patients in the placebo arm. The rates of grade 3/4 serious AEs were 28% (treatment-related, 14%) in the nivolumab arm vs 20% (treatment-related, 6%) in the placebo arm.

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 28, 2025. https://news.bms.com/news/corporate-financial/2025/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---/default.aspx
2. 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):1295. doi:10.1016/j.annonc.2023.10.050
3. FDA approves neoadjuvant/adjuvant nivolumab for resectable non-small cell lung cancer. FDA. October 3, 2024. Accessed March 28, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-neoadjuvantadjuvant-nivolumab-resectable-non-small-cell-lung-cancer