FDA Grants Priority Review to Neoadjuvant Nivolumab Plus Chemotherapy for Resectable NSCLC

The FDA has accepted a supplemental biologics license application (sBLA) for nivolumab (Opdivo) in combination with chemotherapy and granted it priority review for the neoadjuvant treatment of patients with resectable non–small cell lung cancer (NSCLC), according to an announcement by Bristol Myers Squibb.¹

The sBLA, which was given a Prescription Drug User Fee Act target action date of July 13, 2022, is supported by findings from the phase 3 CheckMate-816 clinical trial (NCT02998528).

CheckMate-816 is an international, randomized, open-label study investigating the combination of nivolumab and ipilimumab (Yervoy) or nivolumab plus platinum doublet chemotherapy versus platinum doublet chemotherapy alone in patients with early-stage NSCLC. Interim analysis results from the study show that nivolumab plus chemotherapy showed a statistically significant and clinically meaningful improvement in pathologic complete response (pCR) versus chemotherapy alone when administered prior to surgery, achieving a key primary end point in CheckMate-816.²

Results for the nivolumab/chemotherapy cohort were presented during the American Association for Cancer Research Annual Meeting 2021. In a cohort of 358 patients, the pCR was 24% with nivolumab/chemotherapy compared with 2.2% with chemotherapy alone (odds ration [OR]. 13.94, 99% CI, 3.4%-55.75%; P <.0001).

Assessments of the secondary end points including overall survival (OS), major pathologic response (MPR), and time to death or distant metastases showed that 4 times as many patients treated with nivolumab plus chemotherapy achieved a MPR (36.9%) compared with those 8.9% in of those treated with chemotherapy (OR, 5.70, 95% CI: 3.16-10.26).

Overall, nivolumab/chemotherapy was well-tolerated with no new safety signal observed. Thirty-four percent of those treated with the experimental combination experienced grade 3/4 treatment-related adverse events compared with 37% of the chemotherapy-alone arm. It was also noted by investigators that surgery was not often canceled due to AEs.

In the nivolumab plus chemotherapy arm, 83% of patients underwent surgery versus 75% of the chemotherapy-only arm. Further, a higher percentage of patients who received nivolumab/chemotherapy has R0 resection (83%) compared with the chemotherapy-alone arm (78%).

In addition to patients with early-stage NSCLC being treated in the neoadjuvant setting, nivolumab-based therapies have shown efficacy and safety for the treatment of other lung cancer, bladder cancer, esophageal/gastroesophageal junction cancer, and melanoma.

“While significant progress has been made in how we treat non-small cell lung cancer, there remains a strong need for new options that can prevent recurrence and improve clinical outcomes, especially when a patient’s cancer is caught in earlier stages,” said Abderrahim Oukessou, MD, vice president, thoracic cancers development lead, Bristol Myers Squibb, in a press release.¹ “The FDA’s acceptance of our application marks an important step in our effort to offer patients and physicians the first immunotherapy-based option that can be given before surgery to extend the time patients can continue living without disease progression or recurrence. We look forward to working with the FDA to potentially bring this regimen to patients in the [United States], where lung cancer is the leading cause of cancer deaths.”

_References:

_{1. U.S. Food and Drug Administration accepts for priority review Bristol Myers Squibb’s application for Opdivo (nivolumab) plus chemotherapy as neoadjuvant treatment for resectable non-small cell lung cancer. News release. February 28, 2022. Accessed February 28, 2022. https://bit.ly/3Hu0pmY}

_{2. Neoadjuvant Opdivo (nivolumab) Plus chemotherapy significantly improves pathologic complete response in patients with resectable non-small cell lung cancer in phase 3 CheckMate -816 Trial. News release. April 10, 2021. Accessed February 28, 2022. https://bit.ly/3C3ZFEi}