Neoadjuvant Opdivo Plus Chemotherapy Significantly Improves Pathologic Complete Response in Patients with Resectable Non-Small Cell Lung Cancer in Phase 3 CheckMate -816 Trial

Bristol Myers Squibb announced results from the CheckMate -816 study, which showed that neoadjuvant treatment with three cycles of Opdivo (nivolumab) plus chemotherapy significantly improved pathologic complete response (pCR), a primary endpoint, compared to chemotherapy alone in patients with resectable stage Ib to IIIa non-small cell lung cancer (NSCLC). In the study, 24% of patients treated with Opdivo plus chemotherapy prior to surgery achieved pCR, compared to 2.2% of patients treated with chemotherapy alone (Odds Ratio [OR] 13.94, 99% Confidence Interval [CI]: 3.49–55.75; p<0.0001), with pCR defined as no evidence of cancer cells in their resected tissue as assessed by a blinded independent pathology review. Additionally, Opdivo plus chemotherapy was well tolerated and showed consistent improvements in pCR regardless of PD-L1 expression levels, histologies or stages of disease.

CheckMate -816 represents the first randomized Phase 3 study to show a significant improvement in pathological response with a neoadjuvant immunotherapy combination in patients with resectable NSCLC. The first disclosure of these data will be featured in an oral presentation during the Clinical Trials Plenary Session (Abstract #5218) at the American Association for Cancer Research (AACR) Annual Meeting 2021 on Saturday, April 10, 2021 from 12:30-12:45 p.m. EDT.

“The ultimate goal of treatment in earlier stages of cancer is to prevent the disease from coming back as we work towards a cure for these patients. Unfortunately, even when patients with resectable non-small cell lung cancer undergo surgery, the cancer returns in more than half of patients, and many then die from their disease,” said Nicolas Girard, M.D., professor and head of department, medical oncology, Institut Curie. “The pathologic complete response data from CheckMate -816 give us an early indication of the potential benefit of adding nivolumab to chemotherapy as a neoadjuvant treatment in resectable non-small cell lung cancer, and we hope that these encouraging results eventually translate into improved event-free survival and overall survival for these patients.”

Opdivo plus chemotherapy also demonstrated improvements in key secondary endpoints, including major pathological response (MPR). Four times as many patients treated with Opdivo plus chemotherapy vs. chemotherapy alone achieved MPR (36.9% vs 8.9%; OR 5.70, 95% CI: 3.16-10.26), meaning 10% or less of their tumor cells remained after neoadjuvant therapy.

Three cycles of Opdivo plus chemotherapy were associated with a tolerable safety profile, and no new safety signals were observed. Grade 3–4 treatment-related adverse events were reported in 34% vs. 37% in the Opdivo plus chemotherapy vs. chemotherapy alone arms, respectively. Surgery was rarely canceled due to adverse events, only affecting two patients in each arm of the trial.

Further, in this trial, more patients who received neoadjuvant Opdivo plus chemotherapy underwent surgery (83% vs. 75% with chemotherapy), showing that the addition of Opdivo did not decrease the feasibility of performing surgery. In addition, the number of patients whose tumors were completely resected (R0) was higher with Opdivo plus chemotherapy vs. chemotherapy (83% vs. 78%). Rates of surgery-related adverse events were similar between the two treatment arms.

Opdivo-based treatment regimens have demonstrated durable survival in advanced thoracic cancers. Now, the CheckMate -816 data show that an Opdivo plus chemotherapy regimen has the potential to improve long-term clinical outcomes in earlier stages of non-small cell lung cancer,” said Abderrahim Oukessou, M.D., vice president, thoracic cancers development lead, Bristol Myers Squibb. “The current results from the CheckMate -816 study add to the growing body of evidence that using immunotherapy in cancers that have not yet progressed to metastatic disease may be an important tool for physicians, with four positive Phase 3 trials with Opdivo in resectable cancers to date. We thank the patients and investigators involved in CheckMate -816 and look forward to seeing future results to understand the potential for Opdivo plus chemotherapy to improve event-free survival, the trial’s other primary endpoint, to which we remain blinded.”

More broadly, in earlier stages of NSCLC, Bristol Myers Squibb and collaborators are exploring the use of immunotherapy in the neoadjuvant, adjuvant and peri-operative settings, as well as in association with chemoradiation. The scientific rationale for using immunotherapy in the neoadjuvant setting is twofold: it presents the earliest opportunity to treat cancer cells that have spread in the body without detection, and the presence of a tumor during immunotherapy treatment may enable a stronger immune response, potentially making the treatment more effective.

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