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Microsatellite-instability (MSI) High Colorectal Cancer (CRC)Phase 1/2NCT02178722

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 testing MK-3475 and INCB024360 in people with Microsatellite-instability (MSI) High Colorectal Cancer (CRC) and Endometrial Cancer, run by Incyte Corporation at 24 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
MK-3475 and INCB024360
Could I receive a placebo?
No, everyone receives an active treatment
How many people
444 participants
Where
24 sitesUnited States
Study dates
17 Jul 2014to 6 Nov 2020
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
Show all 66Show fewer
  • 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.
  • Melanoma immune checkpoint-naïve: Subjects must not have received immunotherapy with anti-PD-1, anti-PD-L1, or anti-CTLA-4 therapy. Exception: Prior anti-CTLA-4 in the adjuvant setting would be permitted.
  • Primary refractory melanoma: Subjects must have received prior treatment with anti-PD-1 or anti-PD-L1 therapy (alone or as part of a combination) in the advanced or metastatic setting and have progressive disease as their best response to treatment that is confirmed 4 weeks later.
  • Relapsed melanoma: Subjects must have received prior anti-PD-1 or anti-PD-L1 therapy (alone or as part of a combination) in the advanced or metastatic setting and achieved partial response ore complete response but later have confirmed progressive disease.
  • Subjects enrolling in the primary refractory or relapsed melanoma must be willing to undergo mandatory pretreatment and on-treatment biopsies.
  • Ocular melanoma is excluded.
  • Phase 2 expansion: Transitional cell carcinoma of the GU tract
  • Metastatic or locally advanced and not amenable to curative therapy with disease progression on or after platinum-based chemotherapy or alternative therapy if platinum-based therapy is not appropriate.
  • Prior PD-1 or CTLA-4 targeted therapies are excluded
  • Phase 2 expansion: SCCHN
  • Histologically confirmed metastatic or recurrent squamous cell carcinoma not amenable to local therapy with curative intent (surgery or radiation with or without chemotherapy). Carcinoma of the nasopharynx, salivary gland, or * *Subjects must have received at least 1 prior systemic chemotherapy regimen that must have included a platinum-based therapy.
  • Prior PD-1 or CTLA-4 targeted therapies are excluded.
  • Phase 2 expansion: Ovarian cancer
  • Subjects with FIGO Stage Ic, Stage II, Stage III, Stage IV, recurrent, or persistent (unresectable) histologically confirmed epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube carcinoma.
  • Subjects must have received a platinum-taxane-based regimen as first-line therapy.
  • Prior PD-1 or CTLA-4 targeted therapies are excluded.
  • Borderline, low-malignant-potential epithelial carcinoma per histopathology is excluded.
  • Phase 2 expansion: Relapsed or refractory DLBCL
  • Prior allogeneic stem-cell transplantation is excluded.
  • Must have received > or = 1 prior treatment regimen.
  • Not a candidate for curative therapy or hematopoietic stem-cell transplantation (either due to disease burden, fitness, or preference).
  • Prior PD-1 or CTLA-4 targeted therapies are excluded.
  • Phase 2 expansion: TNBC
  • Histologically confirmed breast adenocarcinoma that is unresectable loco regional, or metastatic
  • Pathologically confirmed as triple negative, source documented, defined as both of the following:
  • Estrogen receptor (ER) and progesterone receptor (PgR) negative.
  • Human epidermal growth factor receptor 2 (HER2) negative as per American Society of Clinical Oncology/College of American Pathologists guidelines.
  • Subject must have received at least 1 prior systemic regimen for advanced or metastatic disease
  • Prior PD-1 or CTLA-4 targeted therapies are excluded.
  • Phase 2 expansion: RCC
  • Subjects with histological or cytological confirmation of clear cell RCC.
  • Not curable by surgery.
  • Subjects must have received prior antiangiogenic therapy.
  • Subjects must not have received prior immunotherapy with anti-PD-1, anti-PD-L1, or anti-CTLA-4 therapy.
  • Phase 2 expansion: MSI high CRC
  • Subjects with histological confirmation of locally advanced unresectable or metastatic MSI high CRC.
  • MSI status is, respectively, determined by examining CRC tumor.
  • Subjects may have received no more than 2 lines of prior therapy for advanced disease.
  • Phase 2 expansion: Gastric Cancer
  • Must have histologically or cytologically confirmed diagnosis of gastric or gastroesophageal junction adenocarcinoma.
  • Must have progression on or after therapy containing platinum/fluoropyrimidine or refused standard therapy.
  • Subjects may have received no more than 2 lines of prior therapy for advanced disease.
  • Prior PD-1 or CTLA-4 targeted therapies are excluded.
  • Phase 2 expansion: HCC
  • Must have histologically or cytologically confirmed diagnosis of HCC (fibrolamellar and mixed hepatocellular/cholangiocarcinoma subtypes are not eligible).
  • Barcelona Clinic Liver Cancer (BCLC) Stage C disease (Llovet et al 1999), or BCLC Stage B disease.
  • Subjects may have received no more than 2 lines of prior therapy for the advanced disease
  • Must have progressed on, refused, or were intolerant of sorafenib.
  • The following are excluded: Subjects with liver transplants, clear invasion of the bile duct or main portal branch(es), or hepatorenal syndrome, or subjects who have required esophageal variceal ablation within 28 days of starting study treatment.
  • Prior PD-1 or CTLA-4 targeted therapies are excluded.
  • Tumor biopsies are required. If a subject has inaccessible lesions, such as in ovarian cancer, HCC, or gastric cancer, or highly vascular lesions, such as RCC, enrollment may be considered with medical monitor approval, and archived tissue may be acceptable.
  • Females of child-bearing potential and males who use adequate birth control through 120 days post dose.

Who cannot join

  • 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.

Trial locations and contacts

24 sites in 1 country.

24 sites in 1 country

United States24 sites

  • University of Michigan Hospital and Health Systems

    Ann Arbor, Michigan, 48109

  • Virginia Cancer Specialists

    Arlington, Virginia, 22031

  • Georgia Cancer Specialists affiliated with Northside Hospital Cancer Institute

    Atlanta, Georgia, 30342

  • University Of Colorado Cancer Center

    Aurora, Colorado, 80045

  • Greater Baltimore Cancer Center

    Baltimore, Maryland, 21204

  • St. Agnes Hospital Cancer Institute

    Baltimore, Maryland, 21229

  • The Center for Cancer and Blood Disorders (RCCA MD LLC- Maryland Division)

    Bethesda, Maryland, 20817

  • The University of Chicago Medicine

    Chicago, Illinois, 60637

  • The Christ Hospital Hematology Oncology, Lindner Research Center

    Cincinnati, Ohio, 45219

  • University Of Texas Southwestern Medical Center At Dallas

    Dallas, Texas, 75390

  • University of Connecticut Health Center Carole And Ray Neag Comprehensive Cancer Center

    Farmington, Connecticut, 06030-1601

  • West Cancer Center

    Germantown, Tennessee, 38120

  • Greenville Health System Cancer Institute

    Greenville, South Carolina, 29605

  • Hackensack University Medical Center - John Theurer Cancer Center

    Hackensack, New Jersey, 07601

  • UC San Diego Moores Cancer Center

    La Jolla, California, 92093

  • The Angeles Clinic and Research Institute

    Los Angeles, California, 90025

  • Miami Cancer Institute at Baptist Health, Inc

    Miami, Florida, 33176

  • Sarah Cannon Research Institute at Tennessee Oncology

    Nashville, Tennessee, 37203-2173

  • University of Pennsylvania Hospital

    Philadelphia, Pennsylvania, 19104

  • Fox Chase Cancer Center

    Philadelphia, Pennsylvania, 19111-2497

  • University of Pittsburgh Medical Center Hillman Cancer Center

    Pittsburgh, Pennsylvania, 15232

  • US Davis Cancer Center

    Sacramento, California, 95817

  • Health Partners Institute

    Saint Louis Park, Minnesota, 55426

  • St. Francis Cancer Center

    Topeka, Kansas, 66618

Other trials in United States

About this study

Official title: 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)

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.

Being tested
MK-3475, INCB024360
Medical subject headings
Microsatellite Instability, Endometrial Neoplasms, Head and Neck Neoplasms, Carcinoma, Hepatocellular, Stomach Neoplasms, Lung Neoplasms, Lymphoma, Carcinoma, Renal Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MK-3475Drug

    IV infusion

  • INCB024360Drug

    Oral daily dosing

Study groups in NCT02178722
Study groupRoleWhat they receive
Phase 1: MK-3475 + INCB024360ExperimentalPhase 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
Receives: Drug: MK-3475; Drug: INCB024360
Phase 2: MK-3475 + INCB024360Experimental(recommended phase 2 dose)
Receives: Drug: MK-3475; Drug: INCB024360

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Approximately 54 months

  2. 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.

    Measured: Approximately 54 months

Secondary outcomes (6)

  1. Phase 2: Duration of Response (DOR)

    Duration of response is the time from the first overall response contributing to an objective response (complete or partial response) for DLBCL to the date of death or the date of first overall response of progressive diseasemeasured (by irRECIST for solid tumors or the Lugano Classification, whichever is earliest.

    Measured: Up to 54 months

  2. Phase 2: Progression Free Survival (PFS)

    Progression-free survival is defined as number of days from the first day of taking study drug to the earlier of death or disease progression by irRECIST v1.1 for select solid tumors and modified Lugano Classification for DLBCL.

    Measured: Up to 54 months

  3. Phase 2: Duration of Disease Control

    The duration of disease control is the time from the treatment start date to the first objective response of PD (by irRECIST v1.1 or Lugano Classification), death, or last tumor assessment date (if PD/death not present), for subjects with best overall response of SD or better.

    Measured: Up to 54 months

  4. Phase 2: Overall Survival (OS)

    Overall survival is determined from the date of first dose until death due to any cause.

    Measured: Up to 54 months

  5. Phase 2: Ordinal Categorical Response Score

    Ordinal categorical response score, determined by radiographic disease assessments per irRECIST v1.1. The 5-category ordinal response endpoint is determined at a given timepoint by classifying response into one of the following groups: 1 = Complete response per irRECIST v1.1 2 = Very good response, defined as > 60% tumor reduction 3 = Minor response, defined as > 30% to ≤ 60% tumor reduction 4 = Stable disease per irRECIST v1.1 5 = Progressive disease per irRECIST v1.1

    Measured: Up to 54 months

  6. Phase 2: Percentage of Participants With Treatment-Emergent Adverse Events (TEAE) and Serious Treatment-Emergent Adverse Events

    Measured: Up to 54 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Jul 2014 (estimated)
  2. Study start17 Jul 2014
  3. Primary completion26 Nov 2018
  4. Study completion6 Nov 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
444 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02178722
Sponsor's protocol ID
INCB 24360-202/ ECHO-202
Status last verified
Feb 2022
First submitted
26 Jun 2014
Last updated
14 Feb 2022
Data monitoring committee
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing MK-3475 and INCB024360 in people with Microsatellite-instability (MSI) High Colorectal Cancer (CRC) and Endometrial Cancer, run by Incyte Corporation at 24 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 66 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 24 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Dec 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase 1: Percentage of Participants With Treatment-Emergent Adverse Events (TEAE) and Serious Treatment-Emergent Adverse Events (time frame: Approximately 54 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02178722.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Feb 2022.

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