Clinical Trial 18832

Cancer Type: Multiple
Interventions:Epacadostat; INCB024360 (Epacadostat); INCB039110; INCB050465

Study Type: Treatment
Phase of Study: Phase I
Investigators:

  • Solmaz Sahebjam

Overview

Study Title

A Platform Study Exploring the Safety, Tolerability, Effect on the Tumor Microenvironment, and Efficacy of INCB Combinations in Advanced Solid Tumors

Summary

The primary purpose of this research study is to determine how safe the study drug INCB039110 is in combination with either epacadostat or INCB050465 in participants who have advanced or metastatic solid tumors. This study will also study the ways in which these drugs are broken down in the body and eliminated, as well as looking at the effects that these study drugs may have on the participant's disease, including changes in their tumor.

Objective

Primary Objective: To evaluate and compare the safety, tolerability, and dose-limiting toxicities (DLTs) of a pharmacologically active dose (PAD) or maximum tolerated dose (MTD) of the different treatments,INCB039110 + epacadostat (INCB024360; Group A) and INCB039110 + INCB050465 (Group B), in subjects with advanced or metastatic solid tumors. Secondary Objectives: To evaluate the efficacy of the different treatments in subjects with advanced or metastatic solid tumors by assessing objective response rate (ORR) per modified RECIST v1.1 (mRECIST) in subjects with confirmed progression on a prior programmed cell death-1 (PD-1) pathway targeted treatment and subjects who are PD-1 pathway targeted treatment naive. To evaluate the efficacy of the different treatments in subjects with select advanced or metastatic solid tumors by assessing progression-free survival (PFS) in subjects with confirmed progression on a prior PD-1 pathway targeted treatment and subjects who are PD-1 pathway targeted treatment naive. To evaluate the efficacy of the different treatments in subjects with select advanced or metastatic solid tumors by assessing duration of response (DOR) in subjects with confirmed progression on a prior PD-1 pathway targeted treatment and subjects who are PD-1 pathway targeted treatment naive. To evaluate changes to the number of tumor-infiltrating lymphocytes (TILs) and the ratio of CD8+lymphocytes to FOXP3+ cells in pre- and post-treatment tumor samples of the different treatments asdetermined by immunohistochemistry (IHC) in subjects with confirmed progression on a prior PD-1 pathway targeted treatment and subjects who are PD-1 pathway targeted treatment naive.

Inclusion Criteria

  • Male or female, age 18 years or older.
  • Willingness to provide written informed consent for the study.
  • Part 1a: Potential participants with histologically or cytologically confirmed advanced or metastatic solid tumors that have failed prior standard therapy (including participant refusal or intolerance).
  • Part 1b: Potential participants with endometrial cancer, gastric cancer, head and neck squamous cell carcinoma, melanoma, microsatellite unstable colorectal cancer, non-small cell lung cancer, pancreatic ductal adenocarcinoma, renal cell carcinoma, triple negative breast cancer, or transitional cell carcinoma of the genitourinary tract that have had disease progression after available therapies for metastatic disease that are known to confer clinical benefit, been intolerant to treatment, or refused standard treatment.
  • Part 1b: Must have documented confirmed disease progression on a prior programmed cell death-1 (PD-1) pathway targeted agent or must be PD-1 pathway-targeted treatment naïve.
  • Has baseline tumor biopsy specimen available or willingness to undergo a pre-treatment tumor biopsy to obtain the specimen.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

  • Exclusion Criteria

  • Laboratory parameters not within the protocol-defined range.
  • Receipt of anticancer medications or investigational drugs within a defined interval before the first administration of study drug.
  • Received an immune-suppressive based treatment for any reason within 14 days prior to the first dose of study treatment.
  • Has not recovered from toxic effect of prior therapy to > Active or inactive autoimmune process.
  • Has received a live vaccine within 30 days of planned start of study therapy.
  • Active infection requiring systemic therapy.