Bristol-Myers Squibb Announces First Presentation of Results for Opdivo (nivolumab) Plus Yervoy (ipilimumab) Combination in Advanced Hepatocellular Carcinoma at ASCO 2019

Opdivo plus Yervoy yielded objective response rate of 31% and median duration of response of 17.5 months

Data demonstrate potential of Immuno-Oncology combination in fourth most common cause of cancer death worldwide

PRINCETON, NJ. USA I June 03, 2019 I Bristol-Myers Squibb Company (NYSE: BMY) today announced first results from the Opdivo (nivolumab) plus Yervoy (ipilimumab) cohort of the Phase 1/2 CheckMate -040 study, evaluating the Immuno-Oncology combination in patients with advanced hepatocellular carcinoma (HCC) previously treated with sorafenib. With a minimum follow-up of 28 months, the blinded independent central review (BICR) objective response rate (ORR) was 31% per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). At the time of data cutoff, the median duration of response (DoR) was 17.5 months (95% CI: 11.1, N/A). These data (Abstract #4012) will be featured at the American Society of Clinical Oncology (ASCO) Annual Meeting 2019 in Chicago in a poster display on Monday, June 3 from 8-11 AM CDT, and in a poster discussion from 3-4:30 PM CDT.

The study randomized patients into three arms evaluating three different dosing schedules of the Opdivo plus Yervoy combination: Opdivo 1 mg/kg and Yervoy 3 mg/kg every three weeks (Q3W) for four cycles, followed by Opdivo 240 mg every two weeks (Q2W) (Arm A); Opdivo 3 mg/kg and Yervoy 1 mg/kg Q3W for four cycles, followed by Opdivo 240 mg Q2W (Arm B); or Opdivo 3 mg/kg Q2W and Yervoy 1 mg/kg every six weeks (Q6W) (Arm C).

Meaningful responses were observed across treatment arms. Patients in Arm A experienced the longest median overall survival (OS) of the cohort at 22.8 months (95% CI: 9.4, N/A) and a 30-month OS rate of 44% (95% CI: 29.5, 57). Opdivo and Yervoy demonstrated a disease control rate (DCR) of 54%, 43% and 49% per BICR using RECIST v1.1 across treatment arms A, B and C, respectively. Across the cohort, 5% of patients experienced a complete response and 26% experienced a partial response. Patient responses were achieved regardless of baseline tumor PD-L1 status. Opdivo plus Yervoy showed an acceptable safety profile and the addition of Yervoy yielded no new safety signals in any treatment arm.

“Hepatocellular carcinoma continues to represent a significant unmet need, as it is often diagnosed in the advanced stage where treatment options are limited and do not currently include the potential of an Immuno-Oncology combination,” said Thomas Yau, M.D., Clinical Associate Professor, Department of Medicine, The University of Hong Kong. “These results indicate the addition of Yervoy to Opdivo elicits promising clinical responses in patients with advanced HCC, reiterating the important potential impact of this combination research.”

Opdivo has been an important treatment option for patients with advanced HCC since 2017, when it became the first Immuno-Oncology agent FDA approved for this aggressive cancer,” said Ian M. Waxman, M.D., development lead, Gastrointestinal Cancers, Bristol-Myers Squibb. “We are encouraged by the efficacy observed with the Opdivo plus Yervoy combination in this cohort of CheckMate -040 and are grateful to the patients and investigators for their participation in this study, without whom this progress would not be possible.”

About CheckMate -040

CheckMate -040 (NCT01658878) is an ongoing Phase 1/2, open-label, multi-cohort study investigating Opdivo or Opdivo-based combinations in patients with advanced HCC with and without chronic viral hepatitis who are naïve, intolerant to or who have progressed during sorafenib therapy.

The Opdivo plus Yervoy cohort of CheckMate -040 is an exploratory cohort evaluating the safety and efficacy of the combination in three different dosing regimens. Primary endpoints include safety and tolerability and ORR based on investigator assessment using RECIST v1.1, which was consistent with the exploratory endpoint of BICR-assessed ORR at 28 months follow-up (29% vs. 31%). Secondary endpoints include DCR, DoR, OS, time to response, time to progression and progression-free survival.

Rates of any grade treatment-related adverse events (TRAEs) were 94%, 71% and 79% in Arms A, B and C, respectively. The most commonly occurring grade 3-4 TRAEs included pruritus (4%, N/A, N/A), rash (4%, 4%, N/A), diarrhea (4%, 2%, 2%), aspartate aminotransferase (AST) increase (16%, 8%, 4%) and lipase increase (12% 6%, 8%). While grade 3-4 TRAEs were most common among patients in Arm A (53%) compared to Arms B and C (29%, 31%), events were considered manageable. Thirteen patients in the cohort (8.9%) had any grade TRAEs leading to discontinuation, eight of whom (5.5%) discontinued due to grade 3-4 TRAEs.

About Hepatocellular Carcinoma

Liver cancer is the fourth most frequent cause of cancer death worldwide and hepatocellular carcinoma (HCC), the most common type of liver cancer, is the fastest rising cause of cancer-related death in the United States. HCC is often diagnosed in the advanced stage, where effective treatment options are limited and the survival benefit provided by the first-line standard of care is less than three months over placebo. While most cases of HCC are caused by hepatitis B virus (HBV) or hepatitis C virus (HCV) infections, metabolic syndrome and nonalcoholic steatohepatitis (NASH) are rising in prevalence and expected to contribute to increased rates of HCC.

Bristol-Myers Squibb: Advancing Oncology Research

At Bristol-Myers Squibb, patients are at the center of everything we do. The focus of our research is to increase quality, long-term survival for patients and make cure a possibility. Through a unique multidisciplinary approach powered by translational science, we harness our deep scientific experience in oncology and Immuno-Oncology (I-O) research to identify novel treatments tailored to individual patient needs. Our researchers are developing a diverse, purposefully built pipeline designed to target different immune system pathways and address the complex and specific interactions between the tumor, its microenvironment and the immune system. We source innovation internally, and in collaboration with academia, government, advocacy groups and biotechnology companies, to help make the promise of transformational medicines, like I-O, a reality for patients.

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 treated more than 35,000 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 65 countries, including the United States, the European Union, Japan and China. 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 unresectable or metastatic melanoma.

OPDIVO® (nivolumab), in combination with YERVOY® (ipilimumab), is indicated for the treatment of patients with unresectable or metastatic melanoma.

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 metastatic small cell lung cancer (SCLC) with progression after platinum-based chemotherapy and at least one other line of therapy. 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 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), as a single agent, 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), in combination with YERVOY® (ipilimumab), is indicated for the treatment of adults and pediatric patients 12 years and older 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.

Checkmate Trials and Patient Populations

Checkmate 037–previously treated metastatic melanoma; Checkmate 066–previously untreated metastatic melanoma; Checkmate 067–previously untreated metastatic melanoma, as a single agent or in combination with YERVOY; Checkmate 017–second-line treatment of metastatic squamous non-small cell lung cancer; Checkmate 057–second-line treatment of metastatic non-squamous non-small cell lung cancer; Checkmate 032–small cell lung cancer; Checkmate 025–previously treated renal cell carcinoma; Checkmate 214–previously untreated renal cell carcinoma, in combination with YERVOY; Checkmate 205/039–classical Hodgkin lymphoma; Checkmate 141–recurrent or metastatic squamous cell carcinoma of the head and neck; Checkmate 275–urothelial carcinoma; Checkmate 142–MSI-H or dMMR metastatic colorectal cancer, as a single agent or in combination with YERVOY; Checkmate 040–hepatocellular carcinoma; Checkmate 238–adjuvant treatment of melanoma.

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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