Phase 1/2 study of epacadostat in combination with durvalumab in patients with metastatic solid tumors
| Autor: | Aung Naing, Alain P. Algazi, Gerald S. Falchook, Benjamin C. Creelan, John Powderly, Seth Rosen, Minal Barve, Niharika B. Mettu, Pierre L. Triozzi, John Hamm, Gongfu Zhou, Chris Walker, Zhiwan Dong, Manish R. Patel |
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| Rok vydání: | 2023 |
| Předmět: |
Adult
Cancer Research Sulfonamides durvalumab Clinical Trials and Supportive Activities Oncology and Carcinogenesis neoplasms Evaluation of treatments and therapeutic interventions epacadostat Antibodies kynurenine Second Primary Oncology Clinical Research 6.1 Pharmaceuticals Oximes Antineoplastic Combined Chemotherapy Protocols Monoclonal PD-1 Public Health and Health Services Humans Oncology & Carcinogenesis Cancer |
| Zdroj: | Cancer, vol 129, iss 1 |
| Popis: | BackgroundTargeting programmed cell death protein 1 (PD-1) and indoleamine 2,3-dioxygenase (IDO1) pathways is an appealing option for cancer treatment.MethodsThe open-label, phase 1/2 ECHO-203 study evaluated the safety, tolerability, and efficacy of the IDO1 inhibitor epacadostat in combination with durvalumab, a human anti-PD-L1 monoclonal antibody in adult patients with advanced solid tumors.ResultsThe most common treatment-related adverse events were fatigue (30.7%), nausea (21.0%), decreased appetite (13.1%), pruritus (12.5%), maculopapular rash (10.8%), and diarrhea (10.2%). Objective response rate (ORR) in the overall phase 2 population was 12.0%. Higher ORR was observed in immune checkpoint inhibitor (CPI)-naïve patients (16.1%) compared with patients who had received previous CPI (4.1%). Epacadostat pharmacodynamics were evaluated by comparing baseline kynurenine levels with those on therapy at various time points. Only the 300-mg epacadostat dose showed evidence of kynurenine modulation, albeit unsustained.ConclusionsEpacadostat plus durvalumab was generally well tolerated in patients with advanced solid tumors. ORR was low, and evaluation of kynurenine concentration from baseline to cycle 2,day 1, and cycle 5,day 1, suggested >300mg epacadostat twice daily is needed to ensure sufficient drug effect.Clinical trial informationA study of epacadostat (INCB024360) in combination with durvalumab (MEDI4736) in subjects with selected advanced solid tumors (ECHO-203) (NCT02318277). |
| Databáze: | OpenAIRE |
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