Combination Epacadostat and Pembrolizumab in NSCLC
Posted: Monday, December 10, 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 non–small cell lung cancer (NSCLC), according to a study published in the Journal of Clinical Oncology. 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-20/KEYNOTE-037 trial enrolled 12 patients with advanced NSCLC, as well as patients diagnosed with advanced cancers of other types. These patients 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.
Overall, 5 of the 12 participants with NSCLC achieved at least a partial response to treatment. Among the five responders, three had adenocarcinoma histology, two tested positive for a KRAS mutation, one had an EGFR mutation, three had PD-L1–positive disease, one had PD-L1–negative disease, and one had IDO1-negative disease. A total of two patients with NSCLC 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.