Phase 3 CheckMate-816 Trial Meets Primary End Point in Resectable NSCLC

October 7, 2020

Significantly more patients treated with nivolumab (Opdivo) plus chemotherapy before surgery demonstrated no evidence of cancer cells in their resected tissue in the trial compared to those treated with chemotherapy alone.

The phase 3 CheckMate-816 trial met a primary end point of pathologic complete response (pCR) in patients with resectable non-small cell lung cancer (NSCLC), according to Bristol Myers Squibb, the conductor of the trial.

Significantly more patients treated with nivolumab (Opdivo) plus chemotherapy before surgery demonstrated no evidence of cancer cells in their resected tissue in the trial compared to those treated with chemotherapy alone. Moreover, the safety profile of nivolumab plus chemotherapy was also consistent with previously reported studies in NSCLC.

Importantly, CheckMate-816 is the first and only phase 3 trial to display a benefit with an immune checkpoint inhibitor in combination with chemotherapy as a neoadjuvant treatment in non-metastatic NSCLC.

“Up to half of patients who undergo surgery for non-metastatic lung cancer will experience disease recurrence,” Mark Awad, MD, PhD, clinical director of the Lowe Center for Thoracic Oncology at Dana-Farber Cancer Institute, said in a press release. “Nivolumab has shown benefit as an adjuvant, or post-surgical, treatment option in other cancer types, and the positive results from CheckMate-816 speak to its potential in the neoadjuvant setting of resectable non-small cell lung cancer. We look forward to following patients in this trial of nivolumab plus chemotherapy as a new way of treating resectable non-small cell lung cancer, with the potential that an improvement in pathologic complete response will lead to extended event-free survival and, ultimately, overall survival.”

The phase 3, randomized, open-label, multi-center trial randomized 358 patients included in the primary analysis to receive either 360 mg of nivolumab plus histology-based platinum doublet chemotherapy every 3 weeks for up to 3 doses, or platinum doublet chemotherapy every 3 weeks for up to 3 doses, followed by surgery. Patients included in the experimental arm of the trial were dosed with up to 3 doses of nivolumab plus chemotherapy prior to surgery, which is a standard number of cycles of therapy in the neoadjuvant setting.

The dual primary end points of the trial are pCR and event-free survival (EFS). Key secondary end points include overall survival (OS), major pathologic response (MPR), and time to death or distant metastases.

Currently, the CheckMate-816 trial remains ongoing to evaluate the other primary end point of EFS, to which the company is blinded, as well as key secondary end points.

Bristol Myers Squibb indicated it will complete a full evaluation of the available data from the CheckMate-816 trial and work with investigators to present the results at an upcoming medical conference. Additionally, the company will discuss potential regulatory options with health authorities.

Of note, the company and collaborators are exploring the use of immunotherapy in the neoadjuvant, adjuvant, and peri-operative settings, as well as in association with chemoradiation. To date, nivolumab has demonstrated improved efficacy in the neoadjuvant and adjuvant treatment of 4 tumor types, including lung cancer, bladder cancer, esophageal/gastroesophageal junction cancer, and melanoma.

Reference:

Opdivo (nivolumab) Plus Chemotherapy Shows Statistically Significant Improvement in Pathologic Complete Response as Neoadjuvant Treatment of Resectable Non-Small Cell Lung Cancer in Phase 3 CheckMate-816 Trial [news release]. Princeton, NJ. Published October 7, 2020. Accessed October 7, 2020. https://news.bms.com/news/details/2020/Opdivo-nivolumab-Plus-Chemotherapy-Shows-Statistically-Significant-Improvement-in-Pathologic-Complete-Response-as-Neoadjuvant-Treatment-of-Resectable-Non-Small-Cell-Lung-Cancer-in-Phase-3-CheckMate--816-Trial/default.aspx