On November 3, 2015 Incyte Corporation (Nasdaq:INCY) reported the first presentation of findings from the ongoing proof-of-concept Phase 1/2 study evaluating epacadostat, Incyte’s selective IDO1 inhibitor, in combination with pembrolizumab, an anti-PD-1 therapy (Press release, Incyte, NOV 3, 2015, View Source [SID:1234507910]). Results evaluating 19 patients for efficacy and 28 patients for safety, indicate a 79 percent (n=15/19) disease control rate (DCR) in evaluable patients with advanced cancers. Responses were observed in all tumor types assessed. In the melanoma group (n=7), four of seven patients treated with the combination of epacadostat and pembrolizumab had an objective response, including 2 complete responses (CRs), with disease control demonstrated in six of the seven patients treated with the combination.

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These results (see Appendix) will be published in the Journal for ImmunoTherapy of Cancer on November 4, 2015. Updated study results—including safety data on 56 patients and efficacy data on 47 patients, inclusive of 19 evaluable melanoma patients—will be presented by Dr. Tara Gangadhar as a late-breaking oral presentation (Abstract #142) on Friday, November 6, 2015 from 12:00-12:15 PM EST at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 30th Anniversary Annual Meeting & Associated Programs. Following the presentation, the updated data will be made available on www.incyte.com.

"These new data underscore the potential of epacadostat to treat advanced forms of cancer when used in combination with an anti-PD-1 therapy," said Rich Levy, MD, Chief Drug Development Officer of Incyte. "We look forward to further evaluating the clinical benefits of the combination of epacadostat and pembrolizumab, both within the planned Phase 3 melanoma study that is expected to begin in the first half of next year, and in other future clinical programs."

About the Study

The ongoing dose-escalation and dose-expansion study of epacadostat in combination with pembrolizumab includes patients with advanced melanoma, renal cell carcinoma (RCC), transitional cell carcinoma (TCC), non-small cell lung cancer (NSCLC), endometrial adenocarcinoma (EA), or squamous cell carcinoma of the head and neck (SCCHN). Patients previously treated with anti-PD-1 or anti-CTLA-4 therapies were excluded.

Study Results

Overall Response Rates (ORR) and Disease Control Rates (DCR) in Advanced Cancers

Adverse events (AEs) included a DLT (grade 3 rash) observed in 1/8 patients with epacadostat 50 mg BID/pembrolizumab 2 mg/kg; no DLTs were observed with epacadostat 100 mg BID/pembrolizumab 2 mg/kg. The most common (≥20%) all grade AEs were fatigue, diarrhea, rash, arthralgia, and nausea; the majority of these were grade 1 or 2. Grade ≥3 immune-related AEs were mucosal inflammation and rash (n=1 [4%] each).

Correlations between biomarker expression and response are being evaluated, and enrollment in expansion cohorts is ongoing.

These data will be discussed as part of Incyte’s previously arranged third quarter 2015 financial results conference call and webcast at 10:00 AM ET on Tuesday, November 3, 2015.

About Epacadostat

Indoleamine 2,3-dioxygenase 1 (IDO1) is an immunosuppressive enzyme that has been shown to induce regulatory T cell generation and activation, and allow tumors to escape immune surveillance. Epacadostat is an orally bioavailable small molecule inhibitor of IDO1 that has nanomolar potency in both biochemical and cellular assays and has demonstrated potent activity in enhancing T lymphocyte, dendritic cell and natural killer cell responses in vitro, with a high degree of selectivity.

Epacadostat has shown proof-of-concept clinical data in patients with unresectable or metastatic melanoma in combination with the CTLA-4 inhibitor ipilimumab, and is currently in four proof-of-concept clinical trials with PD-1 and PD-L1 immune checkpoint inhibitors in a variety of cancer histologies. A Phase 3 study evaluating the combination of epacadostat with pembrolizumab as first-line treatment for patients with advanced or metastatic melanoma is expected to begin in the first half of 2016.