Date: 2017-09-30
Type of
information: Presentation of results at a congress
phase: 1-2
Announcement: presentation of results at the European Society for Medical Oncology (ESMO) Annual Congress 2016, taking place in Copenhagen, Denmark from October 7-11, 2016
Company: Incyte (USA - DE) Merck&Co (USA - NJ)
Product: epacadostat and Keytruda® (pembrolizumab)
Action
mechanism:
- enzyme inhibitor/immunotherapy product/monoclonal antibody/immune checkpoint inhibitor. 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 types.
- Keytruda® (pembrolizumab - MK-3475) is an highly selective monoclonal anti-PD-1 antibody designed to restore the natural ability of the immune system to recognize and target cancer cells by selectively achieving dual ligand blockade (PD-L1 and PD-L2) of the PD-1 protein. By blocking PD-1, pembrolizumab enables activation of the immune system’s T-cells that target cancer by essentially releasing a brake on the immune system.
Disease: advanced tumors
Therapeutic
area: Cancer - Oncology
Country: USA
Trial
details:
- The purpose of the ECHO-202 study is to assess the safety, tolerability, and efficacy when combining MK-3475 and INCB024360 in subjects with certain cancers. This study will be conducted in 2 phases, Phase 1 and Phase 2. 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. (NCT02178722 )
Latest
news:
- Key Findings from the ECHO-202 Advanced Melanoma CohortResults of efficacy evaluable patients (N=54) as of February 27, 2017 include:
-
| ECHO-202 Overall Response Rates (ORR), Disease Control Rates (DCR) and Durability of Response (DoR) in Advanced Melanoma |
| n/N
(%) |
|
|
All Patients |
|
|
Treatment-Naïve
Advanced Melanoma
Patients |
|
|
Treatment-Naïve
Advanced Melanoma
Patients
(epacadostat 100 mg BID) |
| ORR |
|
|
30/54
(56) |
|
|
25/45
(56) |
|
|
18/30
(60) |
|
|
8 CR (15)
22 PR (41) |
|
|
6 CR (13)
19 PR (42) |
|
|
2 CR (7)
16 PR (53) |
| DCR |
|
|
42/54
(78) |
|
|
35/45
(78) |
|
|
Not yet reported |
| DoR |
|
|
28/30 responses ongoing
Median (range) duration of response: 287.5+ (1+ to 763+) days |
- Across all efficacy-evaluable advanced melanoma patients, median progression-free survival (PFS) was 12.4 months, with PFS rates of 70 percent, 54 percent, and 50 percent at 6 months, 12 months, and 18 months respectively. In patients who were treatment-naïve for advanced disease, median PFS has not been reached, with landmark PFS rates of 68 percent, 52 percent, and 52 percent at 6 months, 12 months, and 18 months respectively.
Epacadostat in combination with KEYTRUDA was well-tolerated. The most common (?15 percent) all grade treatment-related adverse events (TRAEs) were fatigue (39 percent), rash (33 percent), pruritus (27 percent), and arthralgia (16 percent). Grade ?3 TRAEs were observed in 17 percent of patients; the most common were increased lipase (n=4), rash (n=3), and increased amylase (n=2). Three patients discontinued for TRAEs. No treatment-related deaths occurred.
- • On July 19, 2016, Incyte announced that updated data from the Phase 1 portion of the ECHO-202/KEYNOTE-037 trial has been accepted for a poster discussion at the European Society for Medical Oncology (ESMO) Annual Congress 2016, taking place in Copenhagen, Denmark from October 7-11, 2016 (Epacadostat Plus Pembrolizumab in Patients With Advanced Melanoma and Select Solid Tumors: Updated Phase 1 Results From ECHO-202/KEYNOTE-037 (Abstract #1110PD).
- • On November 3, 2015, Incyte announced 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. 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.
These results 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 at the Society for Immunotherapy of Cancer ( SITC ) 30th Anniversary Annual Meeting & Associated Programs.
- Study Results
- Overall Response Rates (ORR) and Disease Control Rates (DCR) in Advanced Cancers
|
Evaluable Patients
n (%) |
|
|
Melanoma
n=7 |
|
|
RCC
n=5 |
|
|
TCC
n=2 |
|
|
NSCLC
n=2 |
|
|
EA
n=2 |
|
|
SCCHN
n=1 |
|
|
Total (n) |
| ORR (CR + PR) |
|
|
4 (57) |
|
|
2 (40) |
|
|
1 (50) |
|
|
1 (50) |
|
|
1 (50) |
|
|
1 (100) |
|
|
10 (53) |
| DCR (CR + PR + SD) |
|
|
6 (86) |
|
|
4 (80) |
|
|
1 (50) |
|
|
2 (100) |
|
|
1 (50) |
|
|
1 (100) |
|
|
15 (79) |
- 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.
Is
general: Yes
