Combination of Epacadostat and Pembrolizumab in Advanced Melanoma
Posted: Monday, December 3, 2018
A combination treatment of epacadostat, an indoleamine 2,3-dioxygenase (IDO1) enzyme inhibitor, plus the PD-1 inhibitor pembrolizumab resulted in antitumor activity in patients with advanced melanoma, according to a study published in the Journal of Clinical Oncology. Upregulation of IDO1 has previously been associated with a tumor’s ability to evade notice by the immune system. Tara C. Mitchell, MD, of the University of Pennsylvania, and colleagues also noted “encouraging” antitumor activity when applying this treatment to a variety of advanced solid tumors.
The multicenter, phase I portion of the phase I/II ECHO-202/KEYNOTE-037 trial enrolled 22 patients with advanced melanoma as well as patients diagnosed with advanced cancers of other types. They received 50 mg twice daily of epacadostat in addition to 200 mg of pembrolizumab every 3 weeks. Patients were allowed to continue combination treatment for up to 24 months, followed by treatment with epacadostat alone, until confirmed disease progression, intolerable toxicity, or consent withdrawal.
Of the 22 patients, 12 achieved at least a partial response, with 10 experiencing an ongoing response. Of the 12 responders, 8 had M1c melanoma, 3 had a BRAF mutation, 6 had PD-L1–positive disease, 1 had PD-L1–negative disease, 4 had IDO1-positive disease, and 1 had IDO1-negative disease. Overall, four patients with melanoma achieved stable disease as their best recorded response.
The most common treatment-related adverse events of any grade were fatigue (36%), rash (36%), arthralgia (24%), pruritus (23%), and nausea (21%); adverse events led to treatment discontinuation in 11%. No treatment-related deaths were reported.