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|Epacadostat in Combination with Pembrolizumab Demonstrates Promising Clinical Activity in Multiple Advanced Cancers|
Combination of IDO1 inhibitor plus PD-1 antagonist demonstrates responses and disease control in a broad range of tumor types and is generally well-tolerated with low rates of Grade 3 or higher adverse events
These results (see Appendix) will be published in the
“These new data underscore the potential of epacadostat to treat
advanced forms of cancer when used in combination with an anti-PD-1
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.
Overall Response Rates (ORR) and Disease Control Rates (DCR) in Advanced Cancers
CR = complete response, PR = partial response, SD = stable disease (RECIST 1.1)
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
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.
Except for the historical information set forth herein, the matters set
forth in this press release, including without limitation statements
with respect to the planned commencement of the Phase 3 trial for
epacadostat in combination with pembrolizumab for advanced or metastatic
melanoma, the efficacy of such trial and the effect such trial may have
on patient outcomes, and the evaluation of epacadostat in other clinical
programs, contain predictions and estimates and are forward-looking
statements within the meaning of the "safe harbor" provisions of the
Private Securities Litigation Reform Act of 1995. These forward-looking
statements are based on Incyte’s current expectations and subject to
risks and uncertainties that may cause actual results to differ
materially, including the high degree of risk associated with drug
development, results of further research and development, unanticipated
delays, other market or economic factors and technological advances,
regulatory approval of the transaction and other risks detailed from
time to time in
Preliminary results from a phase 1/2 study of epacadostat (INCB024360) in combination with pembrolizumab in patients with selected advanced cancers
Indoleamine 2,3-dioxygenase 1 (IDO1) is a tryptophan-catabolizing enzyme that is expressed in many cancers and induces immune tolerance by suppressing T-cell responses. Epacadostat is a potent, selective oral inhibitor of IDO1. A dose-escalation study of epacadostat with ipilimumab in patients with advanced melanoma showed favorable ORR, disease control rate (DCR), and PFS in immunotherapy-naïve patients. Preliminary data of epacadostat with pembrolizumab in patients with selected advanced cancers are reported.
This is an ongoing dose-escalation and dose-expansion study of epacadostat with pembrolizumab in patients with Stage IIIB, IV, or recurrent NSCLC, melanoma, transitional cell carcinoma (TCC), RCC, endometrial adenocarcinoma (EA), or SCCHN with a 3+3+3 phase 1 design (NCT02178722). Patients previously treated with anti-PD-1 or anti-CTLA-4 therapies were excluded. Enrollment is complete in the epacadostat 25 mg BID, 50 mg BID, and 100 mg BID cohorts with pembrolizumab 2 mg/kg IV q3 weeks. Expansion cohorts of epacadostat 50 mg BID, 100 mg BID, and 300 mg BID with pembrolizumab 200 mg are enrolling. Safety, tolerability, and investigator-assessed tumor response (RECIST 1.1) were evaluated.
Epacadostat with pembrolizumab was generally well tolerated and efficacy data suggest promising clinical activity. Correlations between biomarker expression and response are being evaluated. Enrollment in expansion cohorts is ongoing. Updated data will be presented.
1) Gibney GT, et al.