Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Study to Explore the Safety, Tolerability and Efficacy of MK-3475 in Combination With INCB024360 in Participants With Selected Cancers

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02178722
Recruitment Status : Active, not recruiting
First Posted : July 1, 2014
Results First Posted : December 19, 2019
Last Update Posted : December 19, 2019
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Incyte Corporation

Tracking Information
First Submitted Date  ICMJE June 26, 2014
First Posted Date  ICMJE July 1, 2014
Results First Submitted Date  ICMJE November 26, 2019
Results First Posted Date  ICMJE December 19, 2019
Last Update Posted Date December 19, 2019
Actual Study Start Date  ICMJE July 17, 2014
Actual Primary Completion Date November 26, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 17, 2019)
  • Phase 1: Percentage of Participants With Treatment-Emergent Adverse Events (TEAE) and Serious Treatment-Emergent Adverse Events [ Time Frame: From study start up to clinical data cut-off date of 26 Nov 2018 (approximately 54 months) ]
    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.
  • Phase 2: Objective Response Rate (ORR) [ Time Frame: Assessed every 9 weeks after the first dose of study treatment for the first 2 assessments (Weeks 9 and 18) then every 12 weeks thereafter until data cut-off date of 26 Nov 2018 (approximately 54 months) ]
    ORR was proportion of participants with best overall response [complete response (CR) or partial response (PR)], per modified Response Evaluation Criteria In Solid Tumors (irRECIST) v1.1 criteria for select solid tumors or modified Lugano Classification for diffuse large B-cell lymphoma (DLBCL).
Original Primary Outcome Measures  ICMJE
 (submitted: June 27, 2014)
  • Phase 1: Number of subjects with dose limiting toxicities (DLTs) of INCB024360 in combination with MK-3475 [ Time Frame: 56 days ]
  • Phase 2: Progression free survival (PFS) [ Time Frame: Assessed every 9 weeks for duration of study participation which is estimated to be 18 months ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 17, 2019)
  • Phase 2: Duration of Response (DOR) [ Time Frame: Assessed every 9 weeks for duration of study participation which is estimated to be a minimum of 18 weeks ]
    Duration of response is the time from the first overall response contributing to an objective response (complete response or partial response) to the date of death or the date of first overall response of progressive disease (whichever is earliest).
  • Phase 2: Progression Free Survival (PFS) [ Time Frame: Response is measured every 9 weeks for duration of study participation which is estimated to be a minimum of 18 weeks ]
    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 (Cheson et al 2014) for DLBCL.
  • Phase 2: Duration of Disease Control [ Time Frame: Assessed every 9 weeks for duration of study participation which is estimated to be a minimum of 18 weeks ]
    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 Cheson et al 2014), death, or last tumor assessment date (if PD/death not present), for subjects with best overall response of SD or bette
  • Phase 2: Ordinal Categorical Response Score [ Time Frame: Assessed every 9 weeks for duration of study participation which is estimated to be a minimum of 18 weeks ]
    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
  • Phase 2: Overall Survival (OS) [ Time Frame: Patients are checked for survival every 12 weeks for duration of study participation which is estimated to be a minimum of 18 weeks ]
    Overall survival is determined from the date of first dose until death due to any cause.
  • Phase 2: Percentage of Participants With Treatment-Emergent Adverse Events (TEAE) and Serious Treatment-Emergent Adverse Events [ Time Frame: Adverse events are assessed every 3 weeks for duration of study participation which is estimated to be 27 months ]
Original Secondary Outcome Measures  ICMJE
 (submitted: June 27, 2014)
  • Objective response rate [ Time Frame: Response is measured every 9 weeks for duration of study participation which is estimated to be 18 months ]
  • Number of subjects with Adverse Events as a Measure of Safety and Tolerability of INCB024360 in combination with MK-3475 [ Time Frame: Adverse events are assessed every 3 weeks for duration of study participation which is estimated to be 18 months ]
  • Ordinal categorical response score [ Time Frame: Response is measured every 9 weeks for duration of study participation which is estimated to be 18 months ]
  • Durability of response [ Time Frame: Response is measured every 9 weeks for duration of study participation which is estimated to be 18 months ]
  • Time to disease progression [ Time Frame: Disease progression is assessed every 9 weeks for duration of study participation which is estimated to be 18 months ]
  • Overall survival (OS) [ Time Frame: Patients are checked for survival every 12 weeks for duration of study participation which is estimated to be 18 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study to Explore the Safety, Tolerability and Efficacy of MK-3475 in Combination With INCB024360 in Participants With Selected Cancers
Official Title  ICMJE 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)
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Microsatellite-instability (MSI) High Colorectal Cancer (CRC)
  • Endometrial Cancer
  • Head and Neck Cancer
  • Hepatocellular Carcinoma (HCC)
  • Gastric Cancer
  • Lung Cancer
  • Lymphoma
  • Renal Cell Carcinoma (RCC)
  • Ovarian Cancer
  • Solid Tumors
  • UC (Urothelial Cancer)
  • Melanoma
  • Bladder Cancer
  • Triple Negative Breast Cancer (TNBC)
Intervention  ICMJE
  • Drug: MK-3475
    IV infusion
  • Drug: INCB024360
    Oral daily dosing
Study Arms  ICMJE
  • Experimental: Phase 1: MK-3475 + INCB024360
    Phase 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
    Interventions:
    • Drug: MK-3475
    • Drug: INCB024360
  • Experimental: Phase 2: MK-3475 + INCB024360
    (recommended phase 2 dose)
    Interventions:
    • Drug: MK-3475
    • Drug: INCB024360
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: June 13, 2018)
444
Original Estimated Enrollment  ICMJE
 (submitted: June 27, 2014)
120
Estimated Study Completion Date  ICMJE August 2020
Actual Primary Completion Date November 26, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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.
      • 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.

Exclusion Criteria:

  • 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02178722
Other Study ID Numbers  ICMJE INCB 24360-202/ ECHO-202
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Incyte Corporation
Study Sponsor  ICMJE Incyte Corporation
Collaborators  ICMJE Merck Sharp & Dohme Corp.
Investigators  ICMJE
Study Director: Mark Jones, MD Incyte Corporation
PRS Account Incyte Corporation
Verification Date December 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP