Phase III CheckMate-816 Trial Demonstrates Significant Improvement in Event-Free Survival with Neoadjuvant Opdivo Plus Chemotherapy in Resectable Non-Small Cell Lung Cancer

Recently, Bristol-Myers Squibb announced the data of the primary endpoint, event-free survival (EFS), from the Phase III clinical trial CheckMate -816. The results showed that, compared with chemotherapy alone, patients with resectable non-small cell lung cancer (NSCLC) who received three cycles of Opdivo combined with chemotherapy before surgery had significantly improved EFS benefits. At the minimum follow-up of 21.0 months, patients who were randomly assigned to receive Nivolumab combined with chemotherapy before surgery had a 37% reduction in the risk of disease recurrence, progression, or death (HR 0.63; 97.38% Confidence Interval [CI]: 0.43-0.91; p=0.0052). The median EFS for patients in the Nivolumab plus chemotherapy group was 31.6 months, while the median EFS for patients in the chemotherapy alone group was 20.8 months.

Moreover, although the current survival data are not yet mature and the analysis has not reached statistical significance, favorable early overall survival (OS) benefits have been observed in the nivolumab plus chemotherapy group (HR 0.57; 99.67% Confidence Interval [CI]: 0.30-1.07). At two years of follow-up, the survival rate was 83% for patients receiving nivolumab plus chemotherapy as neoadjuvant treatment, compared to 71% for those treated with chemotherapy alone. OS follow-up will continue with further analyses planned.

CheckMate -816 is the first Phase III clinical study to demonstrate that immunotherapy-based combination treatment significantly improves EFS and another primary endpoint, the pathological complete response (pCR) rate, in patients with non-small cell lung cancer during the neoadjuvant setting. The EFS data were first presented at the Clinical Studies of Neoadjuvant and Perioperative Immunotherapy session of the 2022 American Association for Cancer Research (AACR) Annual Meeting, held from 23:15 on April 11 to 01:15 on April 12, 2022 Beijing Time (Abstract #CT012), and simultaneously published in The New England Journal of Medicine.

Dr. Nicolas Girard, Investigator of CheckMate –816 and Professor and Director of the Curie Montsouris Thoracic Institute in Paris, stated: "Although some patients with resectable non-small cell lung cancer may be cured, the majority still face a high risk of postoperative recurrence. Therefore, we need effective systemic treatment options to prevent this situation. The results of CheckMate -816 have for the first time demonstrated that neoadjuvant therapy based on an immunotherapy combination regimen can bring clear and significant benefits to these patients compared to chemotherapy alone. In this study, we first observed an improvement in the pathological complete response rate, and now we are seeing an increase in event-free survival, while overall survival is also showing a positive trend of benefit. We are continuously striving toward the ultimate goal of curing patients, and these data indicate that nivolumab combined with chemotherapy has the potential to deliver better long-term survival outcomes for patients."

In the study, the safety of nivolumab combined with chemotherapy as neoadjuvant therapy was consistent with previous research reports, and no new safety signals were observed during the analysis of EFS. The incidence of grade 3-4 treatment-related adverse events in the nivolumab plus chemotherapy group was similar to that in the chemotherapy alone group (34% vs 37%). Additionally, the incidence of grade 3-4 surgery-related adverse events was also similar between the two groups (nivolumab plus chemotherapy group: 11%, chemotherapy alone group: 15%). In the nivolumab plus chemotherapy group, 83% of patients underwent surgery, compared to 75% in the chemotherapy alone group.

CheckMate -816 investigator, Associate Professor of Surgery at McGill University, and attending thoracic and upper gastrointestinal surgeon at Montreal General Hospital, McGill University Health Centre, Jonathan Spicer, stated: "Surgery remains the cornerstone for curing patients with non-small cell lung cancer. The use of nivolumab in combination with chemotherapy as a neoadjuvant treatment allows for shorter, less invasive surgeries with a reduced scope, without increasing complications or adverse events, which is highly significant for thoracic surgeons and their patients. The improvement in surgical outcomes, along with enhanced survival results for patients, is expected to fundamentally transform how surgeons and oncologists collaborate in treating resectable non-small cell lung cancer."

Dr. Abderrahim Oukessou, Vice President of Bristol-Myers Squibb and Head of Thoracic Tumor Development, stated: "Immunotherapy has ushered in a new era of advanced cancer treatment, transforming survival expectations for patients with lung cancer and many other types of tumors. In recent years, with a deeper understanding of the immune system and the biological mechanisms of cancer, we have continued to explore the use of immunotherapy in neoadjuvant, adjuvant, and perioperative settings. The research data from CheckMate -816, including the encouraging early results on overall survival, once again confirm the importance of studying immunotherapy in early-stage cancer. We look forward to continuing to see these scientific advancements bring tangible benefits to patients and their families."

Based on the EFS and pCR results from CheckMate -816, the U.S. FDA approved nivolumab in combination with platinum-doublet chemotherapy (administered once every three weeks for a total of three cycles) in March 2022 as neoadjuvant treatment for adult patients with resectable NSCLC who have tumors ≥4 cm or are lymph node positive. Health regulatory agencies in other countries worldwide are also reviewing the new drug's marketing application.

In the field of non-metastatic non-small cell lung cancer, Bristol-Myers Squibb and its partners are jointly exploring the use of immunotherapy in neoadjuvant, adjuvant, and perioperative settings, as well as in combination with chemoradiotherapy. The use of tumor immunotherapy during the neoadjuvant treatment phase is supported by a dual scientific rationale: firstly, the presence of the tumor during immunotherapy may enhance the immune response, potentially making the treatment for the primary tumor more effective. Secondly, tumor immunotherapy has the opportunity to eliminate hidden micrometastases. To date, Opdivo has demonstrated improved efficacy as a neoadjuvant or adjuvant treatment in four types of tumors, including lung cancer, bladder cancer, esophageal cancer/gastroesophageal junction cancer, and melanoma.

(This indication has not yet been approved in China. The information contained in this material is for reference only, please follow the advice or guidance of doctors or other healthcare professionals.)

About CheckMate -816

CheckMate -816 is a randomized, open-label, multi-center Phase III clinical trial designed to evaluate the efficacy of nivolumab combined with chemotherapy as neoadjuvant treatment compared to chemotherapy alone in patients with resectable Stage IB to IIIA non-small cell lung cancer (according to the 7th edition of the AJCC/UICC staging criteria), regardless of tumor PD-L1 expression levels. In the primary analysis, 358 patients were randomly assigned pre-surgery to receive either nivolumab (360 mg) combined with histology-based platinum doublet chemotherapy (administered every three weeks for a total of three cycles) or platinum doublet chemotherapy alone (administered every three weeks for a total of three cycles), followed by surgical treatment. The primary endpoints of the study are event-free survival and pathological complete response rate. Secondary endpoints include overall survival, major pathological response rate, and time to death or distant metastasis.

About Lung Cancer

Lung cancer is the leading cause of cancer death worldwide. Non-small cell lung cancer (NSCLC) is the most common type, accounting for 84% of all confirmed cases. A majority of NSCLC patients (approximately 60%) are diagnosed without metastasis, and up to half of these cases are resectable. With enhanced screening, this proportion is expected to increase over time. Although many patients with non-metastatic NSCLC can be cured through surgery, 30% to 55% of patients will experience postoperative recurrence and succumb to the disease. Therefore, multiple treatment options are needed, including preoperative (neoadjuvant therapy) and/or postoperative (adjuvant therapy), to improve long-term survival for patients.

About Opdivo

Opdivo is a PD-1 immune checkpoint inhibitor that uniquely harnesses the body's own immune system to help restore anti-tumor immune responses. This characteristic of leveraging the body's own immune system to fight cancer has made Opdivo an important treatment option for multiple types of tumors.

Based on Bristol-Myers Squibb's scientific expertise in the field of Immuno-Oncology (I-O) treatment, Opdivo boasts a globally leading research and development program, covering clinical trials across various stages for multiple types of tumors, including Phase III clinical trials. To date, more than 35,000 patients have received Opdivo treatment as part of its clinical development program. Opdivo’s clinical trials contribute to a deeper understanding of the potential role biomarkers play in guiding patient treatment decisions, particularly in identifying how patients with different levels of PD-L1 expression may benefit from Opdivo.

In July 2014, Opdivo became the world's first PD-1 immune checkpoint inhibitor to receive regulatory approval. Currently, Opdivo has been approved in more than 65 countries and regions, including the United States, the European Union, Japan, and China. Following the initial regulatory approval in October 2015 for the combination of Opdivo® (nivolumab injection) and Yervoy® (ipilimumab injection) for the treatment of metastatic melanoma, this combination therapy has now been approved in over 50 countries and regions, including the United States, the European Union, and China.