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Dual IDO1, PD-L1 inhibition safe for advanced solid tumors
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The addition of the highly selective IDO1 inhibitor epacadostat to the PD-L1 inhibitor durvalumab appeared safe for patients with advanced solid tumors, according to results of the ECHO-203 trial presented at American Association for Cancer Research Annual Meeting.
“IDO1 is an intracellular enzyme that catalyzes the first and rate-limiting step of tryptophan. This degradation is important in the kynurenine pathway,” Aung Naing, MD, FACP, associate professor in the department of investigational cancer therapeutics at The University of Texas MD Anderson Cancer Center, said during a press conference.
The ECHO-203 trial assessed epacadostat (Incyte) plus durvalumab (Imfinzi, AstraZeneca) among 34 patients (median age, 68 years; 60% men) with advanced pancreatic cancer, melanoma, non-small cell lung cancer or head and neck squamous cell carcinoma.
Exclusion criteria included previous treatment with checkpoint inhibitors in unapproved indications.
Patients received doses of epacadostat ranging from 25 mg to 300 mg twice daily, plus 3 mg/kg or 10 mg/kg durvalumab every 2 weeks.
During the 42-day observation period, the most common treatment-related adverse events included fatigue (32%), pruritus (15%), diarrhea (12%), nausea (12%) and rash (12%). Grade 3 or higher adverse events that occurred among more than one patient included fatigue and rash (9% each).
Twenty-nine patients discontinued treatment due to disease progression, adverse event, physician decision or death. Researchers observed one dose-limiting toxicity. No treatment-related deaths were reported.
Median epacadostat exposure was 12.1 weeks (range, 2-121.9). Patients with pancreatic cancer had lower peak exposure of epacadostat than those with other cancer sites.
As of Oct. 29, 2017, 15 patients with pancreatic cancer had efficacy data. At data cutoff, all patients had discontinued treatment due to disease progression, physician decision or death. Researchers observed no responses. Five patients demonstrated stable disease, equating to a disease control rate of 33%. Median duration of disease control was 22 weeks (95% CI, 13-31).
Phase 2 expansion cohorts are evaluating twice-daily 100-mg and 300-mg epacadostat regimens for patients with several malignancies, Naing said. They include NSCLC, HNSCC, urothelial carcinoma, melanoma, gastric or gastroesophageal junction cancer, and triple-negative breast cancer. – by Cassie Homer
References:
Naing A, et al. Abstract CT177. Presented at American Association for Cancer Research Annual Meeting; April 14-18, 2018; Chicago.
Disclosure: Incyte sponsored the study. Incyte and AstraZeneca provided funding for the study. Naing reports research funding from Amplimmune, ARMO Biosciences, Attercor, Bristol-Myers Squibb, EMD Serono, Healios Oncology Nutrition, Incyte, Karyopharm Therapeutics, MedImmune, Merck, NCI, Novartis, and Regeneron, as well as travel and accommodation expenses from ARMO Biosciences. He also reports advisory board roles with CytomX and Novartis.