Study to Explore the Safety, Tolerability and Efficacy of MK-3475 in Combination With INCB024360 in Participants With Selected Cancers
A Phase 1/2 Study Exploring the Safety, Tolerability, and Efficacy of MK-3475 in Combination With INCB024360 in Subjects With Selected Cancers (ECHO-202/KEYNOTE-037)
1 other identifier
interventional
444
1 country
24
Brief Summary
The purpose of this study was to assess the safety, tolerability, and efficacy when combining MK-3475 and INCB024360 in participants with certain cancers. This study was conducted in 2 phases, Phase 1 and Phase 2.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Jul 2014
Longer than P75 for phase_1
24 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 26, 2014
CompletedFirst Posted
Study publicly available on registry
July 1, 2014
CompletedStudy Start
First participant enrolled
July 17, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 26, 2018
CompletedResults Posted
Study results publicly available
December 19, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
November 6, 2020
CompletedFebruary 14, 2022
February 1, 2022
4.4 years
June 26, 2014
November 26, 2019
February 11, 2022
Conditions
Outcome Measures
Primary Outcomes (2)
Phase 1: Percentage of Participants With Treatment-Emergent Adverse Events (TEAE) and Serious Treatment-Emergent Adverse Events
An adverse event is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after a participant provides informed consent. A TEAE is any adverse event either reported for the first time or worsening of a pre-existing event after first dose of study drug. Serious adverse event (SAE) is defined as an event that meets 1 of the following criteria: is fatal or life threatening, results in persistent or significant disability or incapacity, constitutes a congenital anomaly or birth defect, is clinically meaningful (i.e. defined as an event that jeopardizes the participant or requires potential medical or surgical intervention to prevent 1 of the outcomes listed above) or requires inpatient hospitalization or prolongation of existing hospitalization.
Approximately 54 months
Phase 2: Objective Response Rate (ORR)
ORR was percentage of participants with best overall response \[complete response (CR) or partial response (PR)\], per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Approximately 54 months
Secondary Outcomes (6)
Phase 2: Duration of Response (DOR)
Up to 54 months
Phase 2: Progression Free Survival (PFS)
Up to 54 months
Phase 2: Duration of Disease Control
Up to 54 months
Phase 2: Overall Survival (OS)
Up to 54 months
Phase 2: Ordinal Categorical Response Score
Up to 54 months
- +1 more secondary outcomes
Study Arms (2)
Phase 1: MK-3475 + INCB024360
EXPERIMENTALPhase 1: MK-3475 + INCB024360 25 mg twice a day (BID) as starting dose, followed by dose escalations (Phase 1) until recommended phase 2 dose of INCB024360 is determined
Phase 2: MK-3475 + INCB024360
EXPERIMENTAL(recommended phase 2 dose)
Interventions
Eligibility Criteria
You may qualify if:
- Subjects with histologically or cytologically non-small cell lung cancer (NSCLC), melanoma, transitional cell carcinoma of the genitourinary (GU) tract, renal cell cancer, triple negative breast cancer, adenocarcinoma of the endometrium or squamous cell carcinoma of the head and neck (Phase 1).
- Subjects with histologically confirmed melanoma, NSCLC, transitional cell carcinoma of the GU tract, TNBC, SCCHN, ovarian cancer, MSI high colorectal cancer (CRC), RCC, gastric cancer, HCC and DLBCL (Phase 2).
- Life expectancy \> 12 weeks.
- Eastern Cooperative Oncology Group (ECOG) performance status 0 - 1.
- Presence of measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or Lugano Classification for subjects with DLBCL.
- Laboratory and medical history parameters within protocol-defined range.
- For Phase 1: Subjects who have advanced or metastatic disease as noted above that have received at least one prior therapy or have advanced or metastatic disease for which no curative treatment is available may be enrolled.
- For Phase 2 expansion cohorts: Subjects with NSCLC, melanoma (checkpoint inhibitor naïve, primary refractory melanoma, relapsed melanoma), transitional cell carcinoma of the GU tract, SCCHN, ovarian cancer, MSI high CRC, RCC, DLBCL, TNBC, gastric cancer, and HCC.
- Phase 2 expansion: NSCLC
- Subjects who have received at least 1 prior platinum-based therapy. Subjects who have a non-platinum-based regimen may be enrolled with medical monitor approval.
- Tumors with epidermal growth factor receptor mutation positive or anaplastic lymphoma kinase fusion oncogene positive treated with a tyrosine kinase inhibitor are permitted; however, subjects should have progressed on or be intolerant to the targeted therapy.
- Subjects must not have received immunotherapy with programmed death receptor-1 (PD-1) or cytotoxic T-lymphocyte antigen (CTLA-4) targeted therapy.
- Phase 2 expansion: Melanoma
- Documentation of V600E-activating BRAF mutation status.
- Prior systemic therapy requirements.
- +51 more criteria
You may not qualify if:
- Subjects who participated in any other study in which receipt of an investigational study drug or device occurred within 2 weeks or 5 half-lives (whichever is longer) prior to first dose.
- Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways). Exception: Prior anti-CTLA-4 in the adjuvant setting for subjects with melanoma would be permitted.
- Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable.
- Has an active autoimmune disease.
- Has evidence of noninfectious pneumonitis that required steroids or current pneumonitis.
- Live vaccine use within 30 days of first dose of study medication.
- Monoamine oxidase inhibitors.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Incyte Corporationlead
- Merck Sharp & Dohme LLCcollaborator
Study Sites (24)
UC San Diego Moores Cancer Center
La Jolla, California, 92093, United States
The Angeles Clinic and Research Institute
Los Angeles, California, 90025, United States
US Davis Cancer Center
Sacramento, California, 95817, United States
University Of Colorado Cancer Center
Aurora, Colorado, 80045, United States
University of Connecticut Health Center Carole And Ray Neag Comprehensive Cancer Center
Farmington, Connecticut, 06030-1601, United States
Miami Cancer Institute at Baptist Health, Inc
Miami, Florida, 33176, United States
Georgia Cancer Specialists affiliated with Northside Hospital Cancer Institute
Atlanta, Georgia, 30342, United States
The University of Chicago Medicine
Chicago, Illinois, 60637, United States
St. Francis Cancer Center
Topeka, Kansas, 66618, United States
Greater Baltimore Cancer Center
Baltimore, Maryland, 21204, United States
St. Agnes Hospital Cancer Institute
Baltimore, Maryland, 21229, United States
The Center for Cancer and Blood Disorders (RCCA MD LLC- Maryland Division)
Bethesda, Maryland, 20817, United States
University of Michigan Hospital and Health Systems
Ann Arbor, Michigan, 48109, United States
Health Partners Institute
Saint Louis Park, Minnesota, 55426, United States
Hackensack University Medical Center - John Theurer Cancer Center
Hackensack, New Jersey, 07601, United States
The Christ Hospital Hematology Oncology, Lindner Research Center
Cincinnati, Ohio, 45219, United States
University of Pennsylvania Hospital
Philadelphia, Pennsylvania, 19104, United States
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111-2497, United States
University of Pittsburgh Medical Center Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232, United States
Greenville Health System Cancer Institute
Greenville, South Carolina, 29605, United States
West Cancer Center
Germantown, Tennessee, 38120, United States
Sarah Cannon Research Institute at Tennessee Oncology
Nashville, Tennessee, 37203-2173, United States
University Of Texas Southwestern Medical Center At Dallas
Dallas, Texas, 75390, United States
Virginia Cancer Specialists
Arlington, Virginia, 22031, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Limitations and Caveats
Study enrollment was permanently discontinued on 17 May 2018 as a strategic decision.
Results Point of Contact
- Title
- Study Director
- Organization
- Incyte Corporation
Study Officials
- STUDY DIRECTOR
Mark Jones, MD
Incyte Corporation
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 26, 2014
First Posted
July 1, 2014
Study Start
July 17, 2014
Primary Completion
November 26, 2018
Study Completion
November 6, 2020
Last Updated
February 14, 2022
Results First Posted
December 19, 2019
Record last verified: 2022-02
Data Sharing
- IPD Sharing
- Will not share