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Study of Combination Therapy With INCMGA00012 (Anti-PD-1), INCAGN02385 (Anti-LAG-3), and INCAGN02390 (Anti-TIM-3) in Participants With Select Advanced Malignancies

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ClinicalTrials.gov Identifier: NCT04370704
Recruitment Status : Recruiting
First Posted : May 1, 2020
Last Update Posted : December 8, 2021
Sponsor:
Information provided by (Responsible Party):
Incyte Corporation

Tracking Information
First Submitted Date  ICMJE April 29, 2020
First Posted Date  ICMJE May 1, 2020
Last Update Posted Date December 8, 2021
Actual Study Start Date  ICMJE July 28, 2020
Estimated Primary Completion Date July 26, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 29, 2020)
  • Phase 1 and 2 : Participants with treatment-emergent adverse events (TEAE) [ Time Frame: 28 days after end of study approximately 24 months ]
    TEAE is defined as any adverse event either reported for the first time or worsening of a pre-existing event after first dose of study drug
  • Phase 2 : Objective Response Rate [ Time Frame: Every 8 weeks for first 12 months, and every 12 weeks until disease progression; aprroximately 24 months ]
    Defined as the percentage of participants having a Complete Response or Partial Response, will be determined by investigator assessment of radiographic disease assessments per RECIST v1.1.
  • Phase 2 : Duration of Response [ Time Frame: Every 8 weeks for first 12 months, and every 12 weeks until disease progression; aprroximately 24 months ]
    Defined as the time from earliest date of disease response (CR or PR) until earliest date of disease progression, as determined by investigator assessment of radiographic disease per RECIST v1.1, or death from any cause, if occurring sooner than progression.
  • Phase 2 : Disease Control Rate [ Time Frame: Every 8 weeks for first 12 months, and every 12 weeks until disease progression; aprroximately 24 months ]
    Defined as percentage of participants having CR, PR, or SD as best on-study response
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 29, 2020)
  • Phase 1 : Objective Response Rate [ Time Frame: Every 8 weeks for first 12 months, and every 12 weeks until disease progression; aprroximately 24 months ]
    Defined as the percentage of participants having a Complete Response or Partial Response, will be determined by investigator assessment of radiographic disease assessments per RECIST v1.1.
  • Phase 1 : Progression Free Survival [ Time Frame: Every 8 weeks for first 12 months, and every 12 weeks until disease progression; aprroximately 24 months ]
    Defined as the time from date of first dose of study treatment until the earliest date of disease progression, as determined by investigator assessment of objective radiographic disease per RECIST v1.1.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Combination Therapy With INCMGA00012 (Anti-PD-1), INCAGN02385 (Anti-LAG-3), and INCAGN02390 (Anti-TIM-3) in Participants With Select Advanced Malignancies
Official Title  ICMJE A Phase 1-2 Study of Combination Therapy With INCMGA00012 (Anti-PD-1), INCAGN02385 (Anti-LAG-3), and INCAGN02390 (Anti-TIM-3) in Participants With Select Advanced Malignancies
Brief Summary The study will determine Recommended Phase 2 Dose for all study drugs, based on the safety and tolerability of the following combinations: INCAGN02385 + INCAGN02390 and INCAGN02385 + INCAGN02390 + INCMGA00012.
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 Melanoma
Intervention  ICMJE
  • Drug: INCAGN02385
    INCAGN02385 administered intravenously
  • Drug: INCAGN02390
    INCAGN02390 administered intravenously
  • Drug: INCMGA00012.
    INCMGA00012 administered intravenously
Study Arms  ICMJE
  • Experimental: Phase 1 Part 1
    Part 1 will confirm the safety of INCAGN02385 and INCAGN02390 when used in combination. INCAGN02385 will be administered first intravenously followed by INCAGN02390.
    Interventions:
    • Drug: INCAGN02385
    • Drug: INCAGN02390
  • Experimental: Phase 1 Part 2
    Part 2 will confirm the safety of the triple combination of INCAGN02385 + INCAGN02390 + INCMGA00012, following confirmation of the safety of the doublet in Part 1. INCAGN02385 will be administered first intravenously followed by INCAGN02390 and INCMGA00012.
    Interventions:
    • Drug: INCAGN02385
    • Drug: INCAGN02390
    • Drug: INCMGA00012.
  • Experimental: Phase 2
    Phase 2 will determine preliminary efficacy and proof of concept for the combination of INCAGN02385 + INCAGN02390 + INCMGA00012. INCAGN02385 will be administered first intravenously followed by INCAGN02390 and INCMGA00012
    Interventions:
    • Drug: INCAGN02385
    • Drug: INCAGN02390
    • Drug: INCMGA00012.
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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 29, 2020)
52
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 22, 2023
Estimated Primary Completion Date July 26, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Men and women, aged 18 or older.
  • Willingness to provide written informed consent for the study.
  • Phase 1: Participants with locally advanced or metastatic solid tumors for which a PD-1 inhibitor is indicated (locally advanced disease must not be amenable to resection with curative intent) that have failed a PD-1/PD-L1 inhibitor therapy.

    a. PD should be based on imaging done at least 4 weeks apart.

  • Phase 2: Participants with histologically confirmed recurrent Stage III and Stage IV melanoma who relapsed during therapy with anti-PD-1 given as adjuvant therapy.

    1. Participants should have no more than one prior therapy given as adjuvant treatment.
    2. Participants in Stage 1 (n = 13) and Stage 2 (n = 21) of Phase 2 should have documented LAG-3 positive expression (≥ 5%) by IHC.
    3. Participants should be documented BRAF mutation negative.
  • Participants must have fresh biopsy available after completing adjuvant therapy or be willing and able to safely undergo pretreatment tumor biopsies (core or excisional).
  • ECOG performance status 0 or 1.
  • Willingness to avoid pregnancy or fathering children

Exclusion Criteria:

  • Laboratory and medical history parameters outside the protocol-defined range.
  • Known hypersensitivity or severe reaction to any component of the study drugs or formulation components ) within 14 days before study Day 1.
  • Administration of colony-stimulating factors within 14 days before study Day 1.
  • Receipt of a live vaccine within 30 days of planned start of study treatment.
  • Receipt of anticancer medications or investigational drugs within the following intervals before the first administration of study treatment
  • Phase 1:

    1. ≤ 14 days for chemotherapy, targeted small molecule therapy, or radiation therapy. Participants must also not require chronic use of corticosteroids and must not have had radiation pneumonitis as a result of treatment. A 1-week washout is permitted for palliative radiation to non-CNS disease with medical monitor approval.
    2. ≤ 14 days and resolution of all associated toxicities for prior immunotherapy or persistence of active cellular therapy c. < 14 days for prior PD-1 pathway-targeted agents (for Phase 1 and Phase 2).

    d. ≤ 28 days for a prior mAb used for anticancer therapy with the exception of PD-1 pathway-targeted agents and denosumab.

    e. ≤ 7 days for immune-suppressive-based treatment for any reason. f. ≤ 28 days or 5 half-lives (whichever is longer) before the first dose for all other investigational agents or devices. For investigational agents with long half-lives (eg, > 5 days), enrollment before the fifth half-life requires medical monitor approval.

    g. Has not recovered to ≤ Grade 1 from toxic effects of prior therapy (including prior immunotherapy) and/or complications from prior surgical intervention before starting therapy.

  • Phase 2:

    1. Receipt of any anticancer medication other than adjuvant anti-PD-1 therapy.
    2. Receipt of PD-1 pathway-targeted inhibitors within 14 days before the first administration of study treatment.
    3. Unknown LAG-3 status or LAG-3 positive > 0% but < 5%
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: Incyte Corporation Call Center (US) 1.855.463.3463 medinfo@incyte.com
Contact: Incyte Corporation Call Center (ex-US) +800 00027423 eumedinfo@incyte.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04370704
Other Study ID Numbers  ICMJE INCAGN 2385-201
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 Not Provided
Investigators  ICMJE Not Provided
PRS Account Incyte Corporation
Verification Date December 2021

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