On October 3, 2024, the Food and Drug Administration approved nivolumab (Opdivo, Bristol Myers Squibb Company) 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) non-small cell lung cancer (NSCLC) and no known epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements.

Full prescribing information for Opdivo will be posted on Drugs@FDA.

Efficacy and Safety

Efficacy was evaluated in CHECKMATE-77T (NCT04025879), a randomized, double-blind, placebo-controlled multicenter trial in 461 patients with previously untreated and resectable NSCLC (Stage IIA to select stage IIIB [AJCC, 8th edition]). Patients were randomized (1:1) to either nivolumab or placebo, with platinum-based chemotherapy, every 3 weeks for up to 4 cycles (neoadjuvant treatment) followed by either continued single-agent nivolumab or placebo every 4 weeks for up to 13 cycles (adjuvant treatment).

The major efficacy outcome measure was event-free survival (EFS) by blinded independent central review. Median EFS was not reached (95% CI: 28.9, not estimable [NE]) in the nivolumab arm and 18.4 months (95% CI: 13.6, 28.1) in the chemotherapy arm (hazard ratio 0.58 [95% CI: 0.43, 0.78]; p-value 0.00025). At the prespecified interim analysis, overall survival (OS) was not formally tested for statistical significance; however, a descriptive analysis revealed no detriment.

Adverse reactions were similar to those occurring in other clinical trials of nivolumab with chemotherapy. Of those who received neoadjuvant nivolumab, 5.3% were unable to undergo surgery due to adverse reactions compared with 3.5% in the placebo arm. In addition, 4.5% who received neoadjuvant treatment and surgery in the nivolumab arm had delays in surgery due to adverse reactions compared with 3.9% in the placebo arm. See the prescribing information for additional safety information.

The recommended nivolumab dosage is 360 mg every 3 weeks (neoadjuvant treatment) and 480 mg every 4 weeks (adjuvant treatment). Nivolumab should be administered prior to chemotherapy when administered on the same day.

This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, FDA collaborated with the Australian Therapeutic Goods Administration (TGA), the Brazilian Health Regulatory Agency (ANVISA), Health Canada, and Israel’s Ministry of Health (IMoH). The application reviews are ongoing at the other regulatory agencies.

Expedited Programs

This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.

For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email [email protected].

Follow the Oncology Center of Excellence on X: @FDAOncology.