Clinical Trials /

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

NCT04370704

Description:

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.

Related Conditions:
  • Malignant Solid Tumor
  • Melanoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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: 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

Clinical Trial IDs

  • ORG STUDY ID: INCAGN 2385-201
  • NCT ID: NCT04370704

Conditions

  • Melanoma

Interventions

DrugSynonymsArms
INCAGN02385Phase 1 Part 1
INCAGN02390Phase 1 Part 1
INCMGA00012.Phase 1 Part 2

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Phase 1 Part 1ExperimentalPart 1 will confirm the safety of INCAGN02385 and INCAGN02390 when used in combination. INCAGN02385 will be administered first intravenously followed by INCAGN02390.
  • INCAGN02385
  • INCAGN02390
Phase 1 Part 2ExperimentalPart 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.
  • INCAGN02385
  • INCAGN02390
  • INCMGA00012.
Phase 2ExperimentalPhase 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
  • INCAGN02385
  • INCAGN02390
  • INCMGA00012.

Eligibility Criteria

        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%
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase 1 and 2 : Participants with treatment-emergent adverse events (TEAE)
Time Frame:28 days after end of study approximately 24 months
Safety Issue:
Description: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

Secondary Outcome Measures

Measure:Phase 1 : Objective Response Rate
Time Frame:Every 8 weeks for first 12 months, and every 12 weeks until disease progression; aprroximately 24 months
Safety Issue:
Description: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.
Measure:Phase 1 : Progression Free Survival
Time Frame:Every 8 weeks for first 12 months, and every 12 weeks until disease progression; aprroximately 24 months
Safety Issue:
Description: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.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Incyte Corporation

Trial Keywords

  • PD-1 Inhibitors
  • INCAGN02385
  • INCAGN02390
  • INCMGA00012

Last Updated

June 22, 2020