Epacadostat + Opdivo Combo Elicits Durable Clinical Responses in Head and Neck Cancer Patients

Incyte Corporation and Bristol-Myers Squibb Company announced updated data from the ongoing Phase 1/2 ECHO-204 trial evaluating the safety and efficacy of epacadostat, Incyte’s investigational oral selective IDO1 enzyme inhibitor, in combination with Opdivo ^® (nivolumab), Bristol-Myers Squibb’s PD-1 immune checkpoint inhibitor, in multiple advanced solid tumors. These data will be highlighted today in an oral presentation at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago, Illinois.

Efficacy data in patients with squamous cell carcinoma of the head and neck (SCCHN), treatment-naïve advanced melanoma (MEL), ovarian cancer (OC), and colorectal cancer (CRC) will be presented today. The data show that in patients with MEL treated with epacadostat (100 mg or 300 mg) plus nivolumab (n=40), the combined objective response rate (ORR) was 63 percent (25/40), including 2 complete responses (CRs) and 23 partial responses (PRs), and the combined disease control rate (DCR) was 88 percent (35/40). In previously-treated patients with SCCHN who were treated with epacadostat (100 mg or 300 mg) plus nivolumab (n=31), the combined ORR was 23 percent (7/31), including 1 CR and 6 PRs, and the combined DCR was 61 percent (19/31). Responses for MEL and SCCHN were observed regardless of PD-L1 expression and HPV status (in SCCHN), and all responses were ongoing at the data cutoff (February 13, 2017).

ECHO-204 Objective Response Rates (ORR), Disease Control Rates (DCR) and Duration of Response (DoR)

in MEL and SCCHN

n/N
(%)

MEL

SCCHN

All pts

Epacadostat Dose

All Pts

Epacadostat Dose

Total

100 mg BID

300 mg BID

Total

100 mg BID

300 mg BID

ORR

25/40
(63)

6/6
(100)

19/34
(56)

7/31
(23)
1 CR
6 PR

1/7
(14)

6/24

(25)

2 CR
23 PR

all PR

2 CR
17 PR

1 PR

1 CR
5 PR

DCR

35/40

6/6

29/34

19/31

2/7

17/24

(88)

(100)

(85)

(61)

(29)

(71)

DoR

25/25 responses ongoing

8/8 responses ongoing

range 1+ to 41+ weeks

range 8+ to 32+ weeks

Epacadostat plus nivolumab did not demonstrate an efficacy signal in the unselected refractory OC and CRC patient populations.

“The clinical responses in the ECHO-204 trial in patients with melanoma and SCCHN who were treated with the combination of epacadostat and nivolumab further underscore the rationale for studying the therapeutic utility of IDO1 enzyme inhibition plus PD-1 blockade,” said Karl Lewis, M.D., Associate Professor, Division of Medical Oncology, University of Colorado School of Medicine. “These preliminary Phase 1/2 data support further investigation of this novel immunotherapy combination in the planned Phase 3 programs.”

Epacadostat plus nivolumab was generally well-tolerated in patients with select advanced solid tumors. In Phase 1 (dose escalation), 36 patients were enrolled and no dose-limiting toxicities were observed. Among the 230 patients enrolled in Phase 2, the most frequent treatment-related adverse events (TRAEs) (≥10 percent) in patients receiving epacadostat 100 mg BID (69/230) or 300 mg BID (161/230) and Opdivo were rash (35 percent and 32 percent, respectively), fatigue (23 percent and 38 percent, respectively), and nausea (19 percent and 21 percent, respectively). Rash was the most common Grade 3/4 TRAE (10 percent [epacadostat 100 mg BID] and 15 percent [epacadostat 300 mg BID]). TRAEs led to discontinuation in 6 percent (100 mg) and 12 percent (300 mg) of patients. There were no treatment-related deaths.