NCT03182894

Epacadostat in Combination With Pembrolizumab and Azacitidine in Subjects With Metastatic Colorectal Cancer

A Phase IB/II Study of Epacadostat (INCB024360) in Combination With Pembrolizumab (MK-3475) and Azacitidine in Subjects With Chemo-refractory Metastatic Colorectal Cancer

• Status: Withdrawn
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: James J Lee · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Trial Design This is an open label, single-arm, phase IB/II trial to evaluate the safety, tolerability and anti-tumor efficacy of epacadostat (INCB024360) in combination with pembrolizumab (MK-3475) plus azacitidine in patients with chemo-refractory MSS mCRC. The phase 1B portion of the study will evaluate the safety, tolerability and RP2D of epacadostat (INCB024360) in combination with pembrolizumab plus azacitidine in subjects with chemo-refractory MSS mCRC without any further standard treatment options. The phase 2 portion of the study will evaluate the efficacy and safety of epacadostat (INCB024360) in combination with pembrolizumab plus azacitidine in subjects with chemo-refractory MSS mCRC without any further standard treatment options. In both phase IB and phase 2 portions, patients will receive the combination of azacitidine, pembrolizumab and epacadostat (INCB024360) for the first 18 cycles (Cycles 1-18). Beginning with Cycle 19 through Cycle 35, patients will receive the combination of pembrolizumab and epacadostat (INCB024360).

Detailed description

Phase lB Portion: * The phase 1 portion of this study will be a standard "3+3" design. * Pembrolizumab will be administered at 200 mg intravenously (IV) on day 1 of each cycle, every 21 days. * Azacitidine will be administered at 100 mg subcutaneous injection (SQ) daily on days 1-5 of each cycle, every 21 days * Three dose levels of epacadostat (INCB024360) will be explored: dose levels -1, 1 and 2. * The dose level 1 will be the starting dose level. * If the dose level 2 is tolerable without dose limiting toxicities (DLTs), the dose level 2 will be considered the RP2D, and the phase II part will be initiated. * DLT will be monitored during the first 21 days (cycles 1) and will be used for purposes of dose escalation and determination of RP2D. * Definition of DLT: Hematologic Toxicities: * Any Grade 4 thrombocytopenia or neutropenia lasting \> 7 days * Any Grade 3 thrombocytopenia with severe bleeding Nonhematologic Toxicities: o Any Grade 4 toxicity EXCLUDING: Grade 4 abnormal laboratory values with a clear alternative explanation or transient (≤ 72 hours), or without associated clinically significant signs or symptoms based on investigator determination. * Any Grade 3 or 4 AST, ALT, or total bilirubin elevation * Any other Grade 3 toxicity EXCLUDING: * Nausea/vomiting controlled by medical intervention within 72 hours * Grade 3 rash in the absence of desquamation, no mucosal involvement, does not require systemic steroids, and resolves to Grade 1 within 14 days. * Grade 3 abnormal laboratory values with a clear alternative explanation or transient (≤ 72 hours), or without associated clinically significant signs or symptoms based on investigator determination. Phase ll portion: The phase 2 portion of this study is a non-randomized, open-label, single-arm phase II study. The primary objective of this study is to evaluate objective response rate (ORR) using RECIST1.1. Study Procedure * One cycle of therapy is defined as 21 days. * Subjects may continue treatment up to 35 cycles of the study therapy (the combination of azacitidine, pembrolizumab and epacadostat \[INCB024360\] for the first 18 cycles \[Cycle 1 to Cycle 18\], and the combination of pembrolizumab and epacadostat (INCB024360) for the remaining 17 cycles \[Cycle 19 to Cycle 35\]) until evidence of progression of disease (PD) or unacceptable toxicity. * Dose-limiting toxicity (DLT) will be assessed during the first 21 days (cycle 1). * Tumor response will be determined by radiologic measurements by CT and by using RECIST. Assessment of tumor response will be performed every 3 cycles (approximately 9 weeks). * All patients will be evaluated and graded for adverse events according to the NCI Common Terminology for Adverse Events, version 4.0 (NCI-CTCAE). Study Treatment * Pembrolizumab 200 mg will be administered intravenously over 30 minutes on days 1 of each cycle every 21 days. * Azacitidine 100 mg will be administered as subcutaneous injection on days 1-5 of each cycle every 21 days. * Epacadostat (INCB024360) will be administered orally twice a day continuously on days 1-21 of each cycle every 21 days. Two dose levels of epacadostat (INCB024360) will be explored: 100 mg BID and 300 mg BID.

Conditions

• Metastatic Colorectal Cancer

Interventions

Type	Name	Description
DRUG	Epacadostat (INCB024360) in Combination with Pembrolizumab (MK-3475) and Azacitidine (VIDAZA)	Oral Epacadostat (INCB024360) (50, 100, or 300 mg twice per day,on days 1-21 of each cycle, every 21 days) in combination with Pembrolizumab (MK-3475) (200 mg IV on days 1 of each cycle, every 21 days) and Azacitidine (VIDAZA) (100 mg SQ daily on days 1-5 of each cycle, every 21 days)

Timeline

• Start date: 2018-09-30
• Primary completion: 2019-07-30
• Completion: 2020-07-30
• First posted: 2017-06-09
• Last updated: 2018-08-28

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study