Epacadostat Plus Pembrolizumab Shows Early Promise in Advanced RCC

Epacadostat plus pembrolizumab, a novel combination immunotherapy treatment, yielded “encouraging response outcomes” among patients with 0 or 1 prior lines of therapy for advanced renal cell carcinoma (RCC), according to preliminary results from the ongoing phase I/II open-label ECHO-202/KEYNOTE-037 study, presented (abstract 4515) at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting by lead study author Primo Lara, MD, of the University of California Davis Comprehensive Cancer Center in Sacramento.

“Epacadostat plus pembrolizumab was generally well tolerated,” reported Lara.

Epacadostat is an oral inhibitor of indoleamine 2,3-dioxygenase 1, an enzyme that induces T-cell suppression and immune tolerance. Previous research has suggested that in combination with immune checkpoint inhibitors, epacadostat exhibits antitumor activity.

The ECHO-202/KEYNOTE-037 trial is an ongoing study of epacadostat plus pembrolizumab immunotherapy in multiple tumor types. For the kidney cancer cohort, the researchers enrolled adult patients diagnosed with histologically confirmed metastatic or recurrent clear-cell RCC, with ECOG performance status scores of 0 or 1, and no prior immune checkpoint inhibitor therapy.

Thirty-three patients participated in the study. The phase I dose-escalation component of the study (n = 11) involved patients receiving epacadostat (25, 50, 100, or 300 mg twice daily) plus pembrolizumab (2 mg/kg or 200 mg IV every 3 weeks). Maximum tolerated dose was not exceeded. In the phase II portion, 22 patients received epacadostat 100 mg twice daily plus 200-mg pembrolizumab every 3 weeks. Tolerability and safety were assessed in patients receiving at least 1 dose of the combination.

Treatment-related adverse events included fatigue (36%) and rash (36%), as well as arthralgia, diarrhea, pruritus, and pyrexia (12% each). Grade ≥ 3 treatment-related adverse events occurred in 15% of patients. Two patients discontinued treatment following these events. One had grade 3 autoimmune hepatitis; the other had grade 3 aseptic meningitis with headache, nausea, vomiting, and anxiety.

Thirty patients were evaluable for efficacy; 19 (63%) had 0 to 1 prior lines of therapy, and 11 (37%) had 2 or more prior lines of therapy. The objective response rate among patients with 0–1 prior lines of therapy was 47% (9/19), including 1 complete response and 8 partial responses.

A phase III trial is planned for RCC.