Bristol Myers Squibb Highlights Promising Early Data for Opdivo + Yervoy Combination in Advanced Hepatocellular Carcinoma at ASCO 2019

Bristol-Myers Squibb (BMS) recently announced the first data from the Opdivo + Yervoy (OY combination) cohort of the Phase I/II CheckMate-040 study in hepatocellular carcinoma (HCC) at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting held in Chicago. The results confirmed that the combination of Opdivo (Opdivo, generic name: nivolumab) and Yervoy (ipilimumab) has strong efficacy in treating HCC. Both drugs are cancer immunotherapies that leverage the body’s own immune system to fight tumors by targeting different regulatory components of the immune system. Opdivo targets and blocks the PD-1/PD-L1 pathway, while Yervoy targets and blocks CTLA-4.

CheckMate-040 is an ongoing, open-label, multi-cohort study evaluating the efficacy and safety of Opdivo or Opdivo-based combination therapies in patients with advanced hepatocellular carcinoma (HCC), with or without viral hepatitis, who are sorafenib-naïve, intolerant to sorafenib, or have experienced disease progression during sorafenib treatment.

In this study, the OY cohort was an exploratory cohort evaluating the safety and efficacy of three different dosing regimen combinations: (1) Group A: received Opdivo 1 mg/kg and Yervoy 3 mg/kg combination therapy (O1Y3) once every 3 weeks (Q3W) for 4 cycles, followed by Opdivo 240 mg once every 2 weeks (Q2W); (2) Group B: received Opdivo 3 mg/kg and Yervoy 1 mg/kg combination therapy (O3Y1) Q3W for 4 cycles, followed by Opdivo 240 mg (Q2W); (3) Group C: received Opdivo 3 mg/kg Q2W and Yervoy 1 mg/kg once every 6 weeks (Q6W).

With a minimum follow-up of 28 months, the objective response rate (ORR) assessed by blinded independent central review (BICR) was 31%, and the median duration of response (DoR) at the data cutoff was 17.5 months (95% CI: 11.1–N/A). Meaningful responses were observed in all three treatment groups. Among them, patients in Group A experienced the longest median overall survival (OS) in the cohort, at 22.8 months (95% CI: 9.4–N/A), with a 30-month OS rate of 44% (95% CI: 29.5–57).

Evaluated according to the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), the disease control rates (DCR) for the three groups were 54%, 43%, and 49%, respectively. In the overall cohort, 5% of patients achieved complete response, and 26% achieved partial response; response was independent of baseline tumor PD-L1 status. The OY combination demonstrated an acceptable safety profile, with no new safety signals identified in any treatment group.

Thomas Yau, M.D., Associate Professor of Clinical Medicine at the Li Ka Shing Faculty of Medicine, The University of Hong Kong, commented, “HCC remains a significant unmet medical need, as it is often diagnosed at an advanced stage with limited treatment options. The results presented at this conference demonstrate that adding Yervoy to the Opdivo regimen can induce promising clinical responses in patients with advanced HCC, underscoring the significant potential impact of this combination study.”

Ian M. Waxman, Head of Gastrointestinal Cancer Development at Bristol-Myers Squibb, stated, “Opdivo was approved by the U.S. FDA in 2017 as the first immuno-oncology drug for the treatment of this aggressive cancer, and it has since remained an important therapeutic option for patients with advanced hepatocellular carcinoma (HCC). We are highly encouraged by the efficacy observed with the Opdivo plus Yervoy combination in the CheckMate-040 study, and we extend our gratitude to the patients and investigators who participated in this trial.”

Liver cancer is the fourth most common cause of cancer-related deaths worldwide, and hepatocellular carcinoma (HCC) is the most prevalent type of liver cancer, representing the fastest-rising cause of cancer-related mortality in the United States. HCC is typically diagnosed at an advanced stage, with limited effective treatment options; the first-line standard of care offers a survival benefit of less than three months compared to placebo. Although most HCC cases are caused by hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, the rising prevalence of metabolic syndrome and non-alcoholic steatohepatitis (NASH) is expected to drive an increase in HCC incidence. (Compiled by Sina Medicine/newborn)

Reference Source:

1.Bristol-Myers Squibb Announces First Presentation of Results for Opdivo (nivolumab) Plus Yervoy (ipilimumab) Combination in Advanced Hepatocellular Carcinoma at ASCO 20192.https://news.bms.com/press-release/asco19/bristol-myers-squibb-announces-first-presentation-results-opdivo-nivolumab-plus