Opdivo Plus Chemotherapy Showed Improved Progression-Free Survival Versus Chemotherapy in First-Line Lung Cancer Patients with PD-L1

Study also provides important information on I-O plus I-O and I-O plus chemotherapy combinations in a single randomized trial

Results by tumor mutational burden status for both Opdivo-based combinations to be presented

PRINCETON, NJ, USA I June 04, 2018 I Bristol-Myers Squibb Company (NYSE:BMY) today announced results from a part of the Phase 3 CheckMate -227 trial that evaluated Opdivo (nivolumab) plus low-dose Yervoy (ipilimumab) and Opdivo plus chemotherapy versus chemotherapy in patients with first-line advanced non-small cell lung cancer (NSCLC) with PD-L1 expression <1%, across squamous and non-squamous tumor histologies (Part 1b).

$BMY announces new #NSCLC data from Phase 3 combo trial at #ASCO18 #LungCancer

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Data show that Opdivo plus chemotherapy (n=177) extended progression-free survival (PFS) versus chemotherapy (n=186) in patients with PD-L1 expression <1% (HR 0.74; 95% CI: 0.58 to 0.94). PFS is a secondary endpoint for Opdivo plus chemotherapy in Part 1b of the study, and results are based on a descriptive analysis.

In an exploratory analysis of patients with high tumor mutational burden (TMB) ≥10 mutations/megabase (mut/Mb) and PD-L1 expression <1%, the one-year PFS rates were 45% with Opdivo plus low-dose Yervoy (n=38), 27% with Opdivo plus chemotherapy (n=43) and 8% with chemotherapy (n=48). In patients with low TMB (<10 mut/Mb) and PD-L1 <1%, the one-year PFS rate was 18% with both Opdivo plus low-dose Yervoy (n=52) and Opdivo plus chemotherapy (n=54) and was 16% with chemotherapy (n=59).

Hossein Borghaei, D.O., study investigator and chief of thoracic medical oncology at Fox Chase Cancer Center in Philadelphia, said, “For the first time, CheckMate -227 allows the oncology community to look at I-O/I-O and I-O/chemotherapy in one data set. Results show Opdivo plus chemotherapy improved progression-free survival versus chemotherapy in first-line lung cancer patients whose tumors do not express PD-L1. Taken together with the totality of CheckMate -227 data presented to date, the results reinforce that TMB status provides clinically relevant information for Opdivo-based combinations and that Opdivo plus low-dose Yervoy provided durable efficacy in patients with high TMB.”

Results from Part 1b of CheckMate -227 will be presented today from 3:12-3:24 PM CDT during the Lung Cancer—Non-Small Cell Metastatic oral abstract session at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago (Abstract #9001).

Sabine Maier, M.D., development lead, thoracic cancers, Bristol-Myers Squibb, commented, “In today’s evolving NSCLC treatment landscape, the Opdivo-based combination data from CheckMate -227 continue to advance the science of I-O, driving a more precise understanding of predictive biomarkers, such as TMB, to determine who may benefit from I-O combinations.”

In this report, Grade 3-4 treatment-related adverse events (TRAEs) were observed in 25% of patients who received Opdivo plus low-dose Yervoy, 52% with Opdivo plus chemotherapy and 35% with chemotherapy. The most common select Grade 3-4 TRAEs with Opdivo plus low-dose Yervoy were hepatic (8%), gastrointestinal (3%), endocrine (3%), skin (3%), diarrhea (2%), anemia (2%), fatigue (1%), asthenia (1%) and nausea (1%). The most common Grade 3-4 TRAEs with Opdivo plus chemotherapy were anemia (17%), neutropenia (12%), decreased neutrophil count (10%), fatigue (5%), hepatic (3%), decreased appetite (2%), nausea (2%), gastrointestinal (2%), diarrhea (1%), skin (1%) and endocrine (0.6%).

About CheckMate -227

CheckMate -227 is an open-label Phase 3 trial evaluating Opdivo-based regimens versus platinum-doublet chemotherapy in patients with first-line advanced non-small cell lung cancer (NSCLC) across non-squamous and squamous tumor histologies. This program is comprised of three parts:

  • Part 1a: Opdivo plus low-dose Yervoy or Opdivo monotherapy versus chemotherapy in patients whose tumors express PD-L1
  • Part 1b: Opdivo plus low-dose Yervoy or Opdivo plus chemotherapy versus chemotherapy in patients whose tumors do not express PD-L1
  • Part 2: Opdivo plus chemotherapy versus chemotherapy, regardless of PD-L1 or tumor mutational burden (TMB) status

There are two co-primary endpoints in Part 1 for the Opdivo plus low-dose Yervoy combination versus chemotherapy: overall survival (OS) in patients whose tumors express PD-L1 (assessed in patients enrolled in Part 1a); and progression-free survival (PFS) in patients with high TMB ≥10 mut/Mb across the PD-L1 spectrum (assessed in patients enrolled across Parts 1a and 1b).

Data for the co-primary endpoint of PFS were previously presented at the American Association for Cancer Research Annual Meeting 2018 and published in The New England Journal of Medicine.

In Part 1b of this study, patients were randomized 1:1:1 to Opdivo 3 mg/kg every two weeks plus low-dose Yervoy 1 mg/kg every six weeks (n=187); Opdivo 360 mg every three weeks plus histology-based platinum-doublet chemotherapy, followed by Opdivo monotherapy (n=177); and histology-based platinum-doublet chemotherapy every three weeks for up to four cycles (n=186). TMB status was assessed using the validated assay, FoundationOne CDx.

The primary endpoint in Part 2 is OS.

About Tumor Mutational Burden (TMB)

Over time, cancer cells accumulate mutations that are not seen in normal cells of the body. Tumor mutational burden, or TMB, is a quantitative biomarker that reflects the total number of mutations carried by tumor cells. Tumor cells with high TMB have higher levels of neoantigens, which are thought to help the immune system recognize tumors and incite an increase in cancer-fighting T cells and an anti-tumor response. TMB is one type of biomarker that may help predict the likelihood a patient responds to immunotherapies.

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 medicines, including Immuno-Oncology (I-O) therapeutic approaches, for hard-to-treat cancers that could potentially improve outcomes for these patients.

We are leading the integrated scientific understanding of both tumor cell and immune system pathways, 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 24 clinical-stage molecules designed to target different immune system pathways. Our deep expertise and innovative clinical trial designs position us to advance the 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 a patient’s tumor biology can be used as a guide for treatment decisions throughout their journey.

We understand making the promise of transformational medicines like I-O therapies 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.

About Opdivo

Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to uniquely harness the body’s own immune system to help restore anti-tumor immune response. By harnessing the body’s own immune system to fight cancer, Opdivo has become an important treatment option across multiple cancers.

Opdivo’s leading global development program is based on Bristol-Myers Squibb’s scientific expertise in the field of Immuno-Oncology, and includes a broad range of clinical trials across all phases, including Phase 3, in a variety of tumor types. To date, the Opdivo clinical development program has enrolled more than 25,000 patients. The Opdivo trials have contributed to gaining a deeper understanding of the potential role of biomarkers in patient care, particularly regarding how patients may benefit from Opdivo across the continuum of PD-L1 expression.

In July 2014, Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world. Opdivo is currently approved in more than 60 countries, including the United States, the European Union and Japan. In October 2015, the company’s Opdivo and Yervoy combination regimen was the first Immuno-Oncology combination to receive regulatory approval for the treatment of metastatic melanoma and is currently approved in more than 50 countries, including the United States and the European Union.

U.S. FDA-APPROVED INDICATIONS FOR OPDIVO®

OPDIVO® (nivolumab) as a single agent is indicated for the treatment of patients with BRAF V600 mutation-positive unresectable or metastatic melanoma. This indication is approved under accelerated approval based on progression-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

OPDIVO® (nivolumab) as a single agent is indicated for the treatment of patients with BRAF V600 wild-type unresectable or metastatic melanoma.

OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of patients with unresectable or metastatic melanoma. This indication is approved under accelerated approval based on progression-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

OPDIVO® (nivolumab) is indicated for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with progression on or after platinum-based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving OPDIVO.

OPDIVO® (nivolumab) is indicated for the treatment of patients with advanced renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy.

OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of patients with intermediate or poor-risk, previously untreated advanced renal cell carcinoma (RCC).

OPDIVO® (nivolumab) is indicated for the treatment of adult patients with classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and brentuximab vedotin or after 3 or more lines of systemic therapy that includes autologous HSCT. This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

OPDIVO® (nivolumab) is indicated for the treatment of patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) with disease progression on or after platinum-based therapy.

OPDIVO® (nivolumab) is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

OPDIVO® (nivolumab) is indicated for the treatment of adult and pediatric (12 years and older) patients with microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (CRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

OPDIVO® (nivolumab) is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

OPDIVO® (nivolumab) is indicated for the adjuvant treatment of patients with melanoma with involvement of lymph nodes or metastatic disease who have undergone complete resection.

OPDIVO® (10 mg/mL) and YERVOY® (5 mg/mL) are injections for intravenous use.

Checkmate Trials and Patient Populations

Checkmate 067–advanced melanoma alone or in combination with YERVOY® (ipilimumab); Checkmate 037 and 066–advanced melanoma; Checkmate 017–squamous non-small cell lung cancer (NSCLC); Checkmate 057–non-squamous NSCLC; Checkmate 025–renal cell carcinoma; Checkmate 205/039–classical Hodgkin lymphoma; Checkmate 141–squamous cell carcinoma of the head and neck; Checkmate 214–renal cell carcinoma; Checkmate 275–urothelial carcinoma; Checkmate 040–hepatocellular carcinoma, Checkmate 238–adjuvant treatment of melanoma.

Please see U.S. Full Prescribing Information for OPDIVO and YERVOY, including Boxed WARNING regarding immune-mediated adverse reactions for YERVOY.

About the Bristol-Myers Squibb and Ono Pharmaceutical Collaboration

In 2011, through a collaboration agreement with Ono Pharmaceutical Co., Bristol-Myers Squibb expanded its territorial rights to develop and commercialize Opdivo globally except in Japan, South Korea and Taiwan, where Ono had retained all rights to the compound at the time. On July 23, 2014, Ono and Bristol-Myers Squibb further expanded the companies’ strategic collaboration agreement to jointly develop and commercialize multiple immunotherapies – as single agents and combination regimens – for patients with cancer in Japan, South Korea and Taiwan.

About Bristol-Myers Squibb

Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol-Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube and Facebook.

SOURCE: Bristol-Myers Squibb

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