On October 16, 2017 Bristol-Myers Squibb Company (NYSE:BMY) reported data evaluating Opdivo (nivolumab) and Opdivo plus Yervoy (ipilimumab) in previously treated small cell lung cancer (SCLC) patients whose tumors were evaluable for tumor mutation burden (TMB), from the Phase 1/2 CheckMate -032 trial (Press release, Bristol-Myers Squibb, OCT 16, 2017, View Source [SID1234520929]). The primary objective of this trial was objective response rate (ORR) as assessed by a blinded independent central review (BICR), for which results were previously presented; in the pooled intent-to-treat (ITT) population (n=401), the ORR was 11% with Opdivo alone and 22% with the combination. Among the ITT population, 211 (53%) patients had an evaluable TMB result for these analyses and were divided into subgroups of high, medium and low levels of TMB.
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Patients with high TMB who received Opdivo plus Yervoy had an ORR of 46%; the ORR was 16% and 22% in patients with medium and low levels of TMB, respectively. Patients with high TMB who received Opdivo had an ORR of 21%; the ORR was 7% and 5%, in patients with medium and low levels of TMB, respectively. In patients with high TMB who received Opdivo plus Yervoy, 62% were alive at one year; 20% and 23% of patients with medium and low levels of TMB were alive at one year, respectively. In patients with high TMB who received Opdivo, 35% were alive at one year; 26% and 22% of patients with medium and low levels of TMB were alive at one year, respectively. No new safety data were presented in this analysis.
Over time, cancer cells accumulate mutations that are not seen in normal cells of the body. Tumor mutation burden is a measurement of the quantity of mutations carried by tumor cells, and is one type of biomarker that may help predict the likelihood a patient responds to Immuno-Oncology (I-O) therapies.
“These exploratory TMB data from CheckMate -032 are the first to show the potential of using mutation burden to predict response in some patients with the combination of two I-O agents,” said Matthew D. Hellmann, M.D., study investigator, Memorial Sloan Kettering Cancer Center. “Further investigation is warranted to explore the application of this marker across lung cancers, and in the setting of both I-O combination and monotherapy.”
These data will be presented today at the International Association for the Study of Lung Cancer (IASLC) 18th World Conference on Lung Cancer (WCLC) in Yokohama, Japan during the Biomarker for Lung Cancer oral session from 4:15-4:25 PM JST (Abstract # 11063).
Nick Botwood, M.D., development lead, thoracic cancers, Bristol-Myers Squibb, said, “Assessing the effect of TMB on treatment outcomes has been an important part of our ongoing translational medicine research. Based on these exploratory data from CheckMate -032 in previously treated small cell lung cancer, and the growing scientific evidence for this biomarker, we continue to investigate TMB to understand its relevance as a marker to potentially predict outcomes with immunotherapy. We are committed to our ongoing thoracic cancer development program, focused on identifying patients most likely to benefit from immunotherapy.”
About CheckMate -032
CheckMate -032 is an ongoing Phase 1/2 open-label trial, evaluating the safety and efficacy of Opdivo monotherapy 3 mg/kg every two weeks or Opdivo 1 mg/kg plus Yervoy 3 mg/kg every three weeks for four cycles, in advanced or metastatic solid tumors. All patients were treated until disease progression or unacceptable toxicity. The trial included both PD-L1 expressors and non-expressors. The primary objective was objective response rate (ORR) as assessed by a blinded independent central review (BICR). Secondary objectives included safety, overall survival (OS), progression-free survival (PFS) and duration of response (DOR). Biomarker analysis was an exploratory objective.
Progression-free survival data for the TMB-evaluable patient population were also presented at the WCLC. Patients with high TMB who received Opdivo plus Yervoy had a one-year PFS rate of 30%; the rates were 8% and 6% in patients with medium and low TMB levels, respectively. Patients with high TMB who received Opdivo had a one-year PFS rate of 21%; the rate was 3% in patients with medium TMB level; PFS was not evaluable in patents with low TMB level.
About Small Cell Lung Cancer
Small cell lung cancer (SCLC) is one of two main types of lung cancer, which has been the most common cancer in the world for several decades and accounts for about 10% to 15% of all lung cancers. Survival rates vary depending on the stage of the cancer when it is diagnosed, and five-year survival rates tend to be lower than non-small cell lung cancer, as SCLC is faster growing and symptoms are often not detected until the cancer is at an advanced stage. Globally, the five-year survival rate for Stage I SCLC is between 20% and 40%; for Stage IV SCLC, the five-year survival rate drops to 1%.
Bristol-Myers Squibb & Immuno-Oncology: Advancing Oncology Research
At Bristol-Myers Squibb, patients are at the center of everything we do. Our vision for the future of cancer care is focused on researching and developing transformational Immuno-Oncology (I-O) medicines for hard-to-treat cancers that could potentially improve outcomes for these patients.
We are leading the scientific understanding of I-O through our extensive portfolio of investigational compounds and approved agents. Our differentiated clinical development program is studying broad patient populations across more than 50 types of cancers with 14 clinical-stage molecules designed to target different immune system pathways. Our deep expertise and innovative clinical trial designs position us to advance I-O/I-O, I-O/chemotherapy, I-O/targeted therapies and I-O/radiation therapies across multiple tumors and potentially deliver the next wave of therapies with a sense of urgency. We also continue to pioneer research that will help facilitate a deeper understanding of the role of immune biomarkers and how patients’ tumor biology can be used as a guide for treatment decisions throughout their journey.
We understand making the promise of I-O a reality for the many patients who may benefit from these therapies requires not only innovation on our part but also close collaboration with leading experts in the field. Our partnerships with academia, government, advocacy and biotech companies support our collective goal of providing new treatment options to advance the standards of clinical practice.