Bristol-Myers Squibb Announces First Clinical Results of Nivolumab Plus Ipilimumab in Advanced Hepatocellular Carcinoma at ASCO 2019

PRINCETON, New Jersey, June 3, 2019 /PRNewswire/ -- Bristol-Myers Squibb (NYSE:BMY) today announced at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting data from the Phase 1/2 CheckMate -040 clinical studyNivolumabCombinedIpilimumabResults from the first clinical study in patients with advanced hepatocellular carcinoma (HCC) who had previously been treated with sorafenib. After a minimum follow-up of 28 months, the objective response rate (ORR), assessed by the Blinded Independent Central Review Committee (BICR) according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), was 31%. At the data cutoff, the median duration of response (DoR) was 17.5 months (95% CI: 11.1, N/A).

This study randomly assigned patients into three groups to evaluateNivolumabandIpilimumabThree Different Dosing Regimens for Combination Therapy:Nivolumab 1 mg/kg in combinationIpilimumab 3 mg/kg administered once every 3 weeks for 4 consecutive cycles, followed by sequentialNivolumab240 mg, once every 2 weeks (Group A);Nivolumab 3 mg/kg in combinationIpilimumab1 mg/kg treatment, once every 3 weeks, followed by sequential administration after 4 consecutive cycles.Nivolumab240 mg, once every 2 weeks (Group B);Nivolumab 3 mg/kg, once every 2 weeks, in combination withIpilimumab 1 mg/kg, once every 6 weeks (Group C).

Benefit was observed in all treatment groups. Group A had the longest median overall survival (OS) of 22.8 months (95% CI: 9.4, N/A), with a 30-month OS rate of 44% (95% CI: 29.5, 57). Assessed by BICR according to RECIST v1.1,NivolumabandIpilimumabThe disease control rates (DCR) for Groups A, B, and C receiving combination therapy were 54%, 43%, and 49%, respectively. In the entire cohort, 5% of patients achieved complete response and 26% achieved partial response. Objective responses were observed regardless of PD-L1 expression levels.NivolumabCombinedIpilimumabThe treatment regimen demonstrated acceptable safety, with no observations of increasedIpilimumabNew safety signals that have emerged.

“There is a significant unmet need in the treatment of hepatocellular carcinoma, as most patients are already at an advanced stage at diagnosis. Furthermore, current treatment options are limited and do not include promising immuno-oncology (I-O) combination therapies,” said Dr. Thomas Yau, Associate Professor of Clinical Medicine at the Li Ka Shing Faculty of Medicine, The University of Hong Kong.，“The CheckMate -040 study results indicate that,”NivolumabJointIpilimumab"The treatment regimen demonstrates significant clinical efficacy in patients with advanced hepatocellular carcinoma, while also underscoring the critical potential value of research into combination immunotherapy."

“Since 2017NivolumabAs the first immuno-oncology drug approved by the U.S. Food and Drug Administration (FDA) for the treatment of advanced hepatocellular carcinoma, it has become an important therapeutic option for patients with this aggressive cancer.。“Bristol-Myers Squibb GastrointestinalHead of R&D, Oncology Ian M. WaxmanThe doctor stated, “In the CheckMate -040 clinical study,NivolumabCombinationIpilimumab“The efficacy demonstrated by the regimen is highly encouraging. Here, we extend our sincerest gratitude to all patients and investigators who participated in this study; without their contributions, the current progress would not have been possible.”

AboutCheckMate -040

CheckMate-040 is an ongoing, open-label, multi-cohort, phase 1/2 clinical study designed to evaluateNivolumabor withNivolumabEfficacy of Combination Therapy Based on [Regimen] in Patients with Advanced Hepatocellular Carcinoma, Including Those with or without Chronic Viral Hepatitis, Treatment-Naïve to Sorafenib, and Those Intolerant to or with Disease Progression after Prior Sorafenib Therapy

CheckMate-040 exploratorily evaluated three different doses ofNivolumabandIpilimumabSafety and Efficacy of the Combination Regimen. The primary endpoints included safety, tolerability, and the objective response rate (ORR) of 29% assessed by investigators per RECIST v1.1, which was largely consistent with the exploratory endpoint of an ORR of 31% assessed by blinded independent central review (BICR) based on 28 months of follow-up. Secondary endpoints included disease control rate, duration of response, overall survival, time to response, time to tumor progression, and progression-free survival.

Among the treatment groups, the incidence rates of treatment-related adverse events (TRAEs) in Groups A, B, and C were 94%, 71%, and 79%, respectively. The most common Grade 3–4 TRAEs included pruritus (4%, N/A, N/A), rash (4%, 4%, N/A), diarrhea (4%, 2%, 2%), elevated aspartate aminotransferase (AST) levels (16%, 8%, 4%), and elevated lipase levels (12%, 6%, 8%). Although Group A had the highest incidence rate of Grade 3–4 TRAEs (53%) compared to Group B (29%) and Group C (31%), it remained within a manageable range. In the cohort, 13 patients (8.9%) discontinued treatment due to TRAEs of varying grades, including 8 patients (5.5%) who discontinued due to Grade 3–4 TRAEs.

Bristol-Myers Squibb: Advancing the Development of Oncology Research

At Bristol-Myers Squibb, our guiding principle is to put patients first in everything we do. Our vision is to improve the quality of life for cancer patients, enable long-term survival, and make cures possible. Driven by translational science, we leverage our deep scientific expertise in oncology and immuno-oncology (I-O) through a distinctive multidisciplinary collaborative approach to deliver personalized, innovative treatment solutions that meet diverse patient needs. Our researchers are dedicated to developing a diverse and targeted pipeline of therapies designed to address the complex and specific interactions among tumors, the tumor microenvironment, and the immune system by targeting various immune signaling pathways. Beyond fostering internal innovation, we actively promote collaboration and exchange with academia, government entities, patient organizations, and biotechnology companies. Just as immuno-oncology (I-O) therapies continue to advance, we remain committed to empowering patients and fulfilling our promise of transformative medicine.

About Opdivo^®（Nivolumab)

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 intrinsic immune system to combat cancer enables Opdivo^®Has become an important treatment option for multiple tumor types.

Leveraging Bristol-Myers Squibb’s scientific expertise in the field of immuno-oncology (I-O) therapy, Opdivo^®Possesses globally leading R&D programs, covering clinical trials across various stages for multiple tumor types, including Phase III clinical trials. To date, Opdivo^®clinical development programs have enrolled more than 35,000 patients. Opdivo^®Clinical trials help deepen the understanding of the potential indicative role of biomarkers in guiding treatment selection for patients, particularly in identifying how patients with different PD-L1 expression levels may benefit from Opdivo^®benefit from.

July 2014, Opdivo^®As the world’s first PD-1 immune checkpoint inhibitor approved by regulatory authorities, Opdivo currently^®Approved in more than 65 regions, including the United States, the European Union, Japan, and China. In October 2015, Opdivo^®The combination therapy with ipilimumab for the treatment of melanoma became the first immuno-oncology (I-O) drug combination approved by regulatory authorities, and it has currently been approved in more than 50 regions, including the United States and the European Union.

Note:

Nivolumab (Opdivo^®，nivolumab) approved only in mainland China for the treatment of epidermal growth factor receptor (EGFR) gene mutation-negative and anaplastic lymphoma kinase (ALK) negative, locally advanced or metastatic non-small cell lung cancer with disease progression or intolerance after prior platinum-based chemotherapy (NSCLC) Adult patients.

Ipilimumab (ipilimumab) has not yet been approved for marketing in mainland China.