Epacadostat/ Nivolumab Shows Promising Efficacy for Melanoma, Head and Neck Cancer

Karl D. Lewis, MD

The combination of the IDO inhibitor epacadostat and nivolumab (Opdivo) demonstrated promising signs of activity for patients with squamous cell carcinoma of the head and neck (SCCHC) and those with melanoma, according to findings from the phase I/II ECHO-204 study presented at the 2017 ASCO Annual Meeting.

The combination of epacadostat and nivolumab demonstrated an objective response rate (ORR) of 63% and a complete response (CR) rate of 5% for patients with treatment-naive melanoma, in the multi-arm, open-label trial. In those with SCCHC, the ORR was 23% and the CR rate was 3%. The combination was not effective in unselected patients with ovarian cancer and colorectal cancer (CRC).

"Epacadostat plus nivolumab was active in phase II melanoma and squamous cell carcinoma of the head and neck cohorts," said study coauthor Karl D. Lewis, MD, associate professor, Division of Medical Oncology, University of Colorado Anschutz Medical Campus. "Response was observed regardless of PD-L1 expression and HPV status. All responses were ongoing at data cutoff."

In the phase I portion of the study, the epacadostat dose was escalated from 25 mg twice daily to 300 mg twice daily. In the phase II portion, patients received a 100 mg twice daily and 300 mg twice daily dose of epacadostat. Nivolumab was originally administered at 3 mg/kg every 2 weeks, which was switched to 240 mg IV every 2 weeks in the phase II portion of the study. The findings presented at ASCO for safety were from both portions of the study while the efficacy findings were from just the phase II cohort.

For patients with untreated melanoma (N = 40), the ORR with the 100-mg dose (n = 6) of epacadostat was 100%, which consisted entirely of partial responses. With the 300-mg dose (n = 34), the ORR was 56% and the CR rate was 6%. The disease control rate (DCR; ORR plus stable disease) was 85%. In those with PD-L1—positive tumors (n = 7), the ORR was 71% versus 29% in the PD-L1–negative group (n = 7). All responses were ongoing, with a median duration of 16+ weeks.

In the SCCHN group, in which patients had received ≤2 prior lines of therapy, the ORR with the 100-mg dose (n = 7) of epacadostat was 14%, there were no CRs, and the DCR was 61%. In the 300-mg arm (n = 24), the ORR was 25%, with 1 CR and a DCR of 71%. Patients with PD-L1—positive tumors (n = 10) had an ORR of 30% and those with negative tumors (n = 8) had an ORR of 13%. All responses were ongoing at the analysis, with a median greater than 24+ weeks.

In 29 evaluable patients with ovarian cancer, the ORR was 14% and the DCR was 31%. There was 1 CR in a patient with treatment naive, BRCA-negative, PD-L1—positive disease. In 26 patients with CRC, those with microsatellite instability (MSI) had an ORR of 25% and those with microsatellite stable disease did not experience a response.

"Epacadostat plus nivolumab did not demonstrate an efficacy signal in the unselected populations of refractory ovarian cancer and CRC patients," Lewis said of the results. Regarding future investigations, he noted that the "preliminary safety and efficacy results support further investigation of nivolumab and epacadostat in treatment-naive patients with melanoma and in patients with SCCHN."

Across all patients, adverse events (AEs) of any grade were experienced by 83% of individuals treated with the 100-mg dose of epacadostat and 73% with the 300-mg dose. Grade 3/4 AEs were experienced by 25% and 27% of those in the 100 mg and 300 mg dose arms, respectively. Treatment-related AEs led to discontinuation for 6% of those in the 100-mg group versus 12% for the 300-mg arm. The most common grade 3/4 treatment-related AEs were rash, which occurred in 10% of those in the 100-mg arm and for 15% with the 300-mg dose.

"ECHO-204 study results show that epacadostat plus nivolumab was generally well tolerated among patients with select advanced solid tumors," Lewis said. "Treatment-related grade 3 rash rate was higher with epacadostat 300 mg versus 100 mg twice daily. As was the rate of treatment-related AEs leading to discontinuation."

The phase II portion of the ECHO-204 study continues to enroll participants (NCT02327078). The trial is including several types of solid tumors, including the currently unreported arms of patients with non—small cell lung cancer, glioblastoma, and lymphoma.

Perez RP, Riese JM, Lewis KD, et al. Epacadostat plus nivolumab in patients with advanced solid tumors: Preliminary phase I/II results of ECHO-204. J Clin Oncol. 2017;35 (suppl; abstr 3003).

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