Pembrolizumab Plus Epacadostat Yields Durable Response in Advanced Melanoma: ESMO

Results of a combination trial evaluating epacadostat with pembrolizumab in advanced melanoma, to be presented at the upcoming European Society for Medical Oncology (ESMO) 2017 Congress, has found that the treatment is well tolerated and has promising clinical activity. These results will raise competition for ipilimumab—nivolumab in melanoma treatment.

The results, to be presented on September 9, include results collected from 54 evaluable patients who participated in an ongoing phase 1/2 study, with results collected as of February 27, 2017. Patients previously treated with checkpoint inhibitors were excluded from the trial. For the phase 1 study, 22 patients received 25 mg, 50 mg, 100 mg, or 300 mg oral epacadostat twice a day, with 2 mg/kg or 200 mg/kg intravenous pembrolizumab, every 3 weeks. Forty-two patients in the phase 2 study received the following dose: 100 mg epacadostat twice a day and 200 mg pembrolizumab every 3 weeks.

The median progression-free survival (PFS) in patients with advanced melanoma was 12.4 months, with rates of 70% at 6 months, 54% at 12 months, and 50% at 18 months. Treatment-naïve patients had not reached median PFS at the time of data collection.

Across the 54 patients, an overall response rate (ORR) of 56% was noted, with a 15% complete response (CR) and 41% partial response (PR). The ORR in treatment-naïve patients was 56% (6 CR and 19 PR), and in treatment-naïve patients receiving 100 mg epacadostat, ORR was 60% (2 CR and 16 PR).

The responses were independent of the patients’ B-RAF mutation or expression of programmed death ligand-1 expression.

The most common (more than 15%) treatment-related adverse events (TRAEs) were fatigue (39%), rash (33%), pruritis (27%), and arthralgia (16%). Grade 3 or higher TRAEs were observed in 17% of patients, with the most common being lipase, rash, and increased amylase, with 3 patients discontinuing treatment following TRAE.

“We are encouraged by these additional data from our ECHO-202 trial, which demonstrate robust and durable responses in patients with advanced melanoma treated with the combination of epacadostat and Keytruda,” said Steven Stein, MD, chief medical officer of Incyte, which is codeveloping this treatment with Merck. “These results further underscore the potential of this novel immunotherapy combination, and we look forward to reporting more detailed results from this study at ESMO next month.”

Comparing the results of this study with the CheckMate 067 results presented at the annual meeting of the American Society of Clinical Oncology, patients in the current study seem to have significantly lower higher-grade adverse events. The TRAEs associated with the combination of ipilimumab and nivolumab resulted in nearly 40% of patients in the phase 3 pausing treatment. The median PFS with this combination was 11.7 months.

Epacadostat, a selective inhibitor of the indoleamine 2,3-dioxygenase 1 or IDO1 enzyme that helps cancer cells evade immunosurveillance, is also being evaluated in other solid tumors and for hematological malignancies.