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Published on: April 22, 2019
Phase I/II trial of BMS-986,205 and nivolumab as first line therapy in hepatocellular carcinoma
Jasmine C Huynh1, May Cho2, Arta Monjazeb3
1Division of Hematology and Oncology, Davis Comprehensive Cancer Center, University of California, Sacramento, CA, 95817, USA.
Background:
Indoleamine-2,3-dioxygenase (IDO) helps orchestrate immune suppression and checkpoint inhibitor resistance in hepatocellular carcinoma (HCC). BMS-986,205 is a novel oral drug that potently and selectively inhibits IDO. This Phase I/II study evaluated the safety and tolerability of BMS-986,205 in combination with nivolumab as first-line therapy in advanced HCC.
Methods:
Adults with untreated, unresectable/metastatic HCC received BMS-986,205 at two dose levels (50-100 mg orally daily) in combination with fixed dose nivolumab (240mg/m2 IV on Day 1 of each 14-day cycle). The primary objective was to determine the safety and tolerability of this combination; secondary objectives were to obtain preliminary efficacy.
Results:
Eight patients received a total of 91 treatment cycles in the dose escalation phase. All patients were Child Pugh A and 6 patients had underlying viral hepatitis. In the 6 evaluable patients, no dose-limiting toxicities (DLTs) were observed. The most common treatment-related adverse events (TRAEs) were aspartate transaminase (AST) and alanine transaminase (ALT) elevation (3 patients) and diarrhea, maculopapular rash and increased alkaline phosphatase (2 patients each). Grade 3 events were diarrhea and AST elevation (1 patient), and hyperglycemia and pancreatitis requiring treatment discontinuation (1 patient). No grade 4-5 events occurred. Partial response was observed in 1 patient (12.5%) and stable disease in 3 patients (37.5%), yielding a disease control rate of 50%. Median PFS was 8.5 weeks; median OS was not reached.
Conclusion:
Combination BMS-986,205 and nivolumab showed a manageable safety profile with durable benefit as first-line therapy in a meaningful subset of advanced HCC patients.
Insights
The combination of BMS-986,205 and nivolumab demonstrated a manageable safety profile for advanced hepatocellular carcinoma (HCC). This first-line therapy showed durable benefit in a subset of patients with this liver cancer.
Area of Science:
- Hepatocellular Carcinoma Research
- Immunotherapy
- Drug Development
Background:
- Indoleamine-2,3-dioxygenase (IDO) is implicated in immune suppression and resistance to checkpoint inhibitors in hepatocellular carcinoma (HCC).
- BMS-986,205 is a novel oral drug designed for potent and selective IDO inhibition.
Purpose of the Study:
- To evaluate the safety and tolerability of BMS-986,205 in combination with nivolumab.
- To assess preliminary efficacy as a first-line therapy for advanced HCC.
Main Methods:
- Phase I/II study involving adult patients with untreated, unresectable/metastatic HCC.
- BMS-986,205 (50-100 mg daily) combined with nivolumab (240 mg/m² every 14 days).
Main Results:
- Eight patients received treatment; no dose-limiting toxicities observed.
- Most common treatment-related adverse events included elevated liver enzymes and diarrhea.
- One partial response (12.5%) and stable disease in three patients (37.5%) observed; 50% disease control rate.
Conclusions:
- Combination therapy of BMS-986,205 and nivolumab exhibits a manageable safety profile.
- This combination offers durable benefit for a subset of advanced HCC patients as first-line treatment.
