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 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: INCAGN 2385-2012021-005775-39
• Study Type: interventional
• Target: 61
• Locations: 2 countries
• Sites: 17

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.

Conditions

Melanoma

Keywords

PD-1 Inhibitors; INCAGN02385; INCAGN02390; INCMGA00012; Retifanlimab

Outcome Measures

Primary Outcomes (5)

• Phases 1 & 2: Participants with treatment-emergent adverse events (TEAEs)

  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

  28 days after end of study approximately 24 months

• Phase 2 Cohort A and B: Objective Response Rate (ORR)

  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.

  Every 8 weeks for first 12 months, and every 12 weeks until disease progression; approximately 24 months

• Phase 2 Cohort A and B: Duration of Response (DOR)

  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.

  Every 8 weeks for first 12 months, and every 12 weeks until disease progression; approximately 24 months

• Phase 2 Cohort A and B: Disease Control Rate (DCR)

  Defined as percentage of participants having CR, PR, or SD as best on-study response.

  Every 8 weeks for first 12 months, and every 12 weeks until disease progression; approximately 24 months

• Phase 2 Cohort A and B: Progression-free Survival (PFS)

  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

  Every 8 weeks for first 12 months, and every 12 weeks until disease progression; approximately 24 months

Secondary Outcomes (3)

• Phase 1 : Objective Response Rate

  Every 8 weeks for first 12 months, and every 12 weeks until disease progression; aprroximately 24 months

• Phase 1 : Progression Free Survival

  Every 8 weeks for first 12 months, and every 12 weeks until disease progression; aprroximately 24 months

• Phase 1: Disease Control Rate (DCR)

  Every 8 weeks for first 12 months, and every 12 weeks until disease progression; approximately 24 months

Study Arms (6)

Phase 1 Part 1

EXPERIMENTAL

Part 1 will confirm the safety of INCAGN02385 and INCAGN02390 when used in combination. INCAGN02385 will be administered first intravenously followed by INCAGN02390.

Drug: INCAGN02385; Drug: INCAGN02390

Phase 1 Part 2

EXPERIMENTAL

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.

Drug: INCAGN02385; Drug: INCAGN02390; Drug: INCMGA00012.

Phase 2 Cohort A

EXPERIMENTAL

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

Drug: INCAGN02385; Drug: INCAGN02390; Drug: INCMGA00012.

Phase 2 Cohort B

EXPERIMENTAL

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

Drug: INCAGN02385; Drug: INCAGN02390; Drug: INCMGA00012.

Phase 1 Part 3

EXPERIMENTAL

Part 1 will confirm the safety of INCAGN02385 + INCAGN02390 + INCMGA00012 when used in combination.

Drug: INCAGN02385; Drug: INCAGN02390; Drug: INCMGA00012.

Phase 1 Part 4

EXPERIMENTAL

Part 1 will confirm the safety of INCAGN02385 + INCAGN02390 + INCMGA00012 in combination.

Drug: INCAGN02385; Drug: INCAGN02390; Drug: INCMGA00012.

Interventions

INCAGN02385 DRUG

INCAGN02385 administered intravenously

Phase 1 Part 1; Phase 1 Part 2; Phase 1 Part 3; Phase 1 Part 4; Phase 2 Cohort A; Phase 2 Cohort B

INCAGN02390 DRUG

INCAGN02390 administered intravenously

Phase 1 Part 1; Phase 1 Part 2; Phase 1 Part 3; Phase 1 Part 4; Phase 2 Cohort A; Phase 2 Cohort B

INCMGA00012. DRUG

INCMGA00012 administered intravenously

Phase 1 Part 2; Phase 1 Part 3; Phase 1 Part 4; Phase 2 Cohort A; Phase 2 Cohort B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Phase 1 Parts 1-4): Participants with locally advanced or metastatic solid tumors (locally advanced disease must not be amenable to resection with curative intent) that have failed available therapies, including anti-PD-(L)1 therapy if applicable, that are known to confer clinical benefit, or who are intolerant to, or ineligible for standard treatment. Prior anti-PD-(L)1 therapy should not have been discontinued because of intolerance.
• Phase 2, Cohort A:
• Participant with histologically confirmed unresectable/metastatic melanoma, whose disease failed prior anti-PD-(L)1 therapy (alone or as part of a combination) and meeting one of the following criteria:
• Participant who failed prior adjuvant anti-PD-(L)1 therapy for resectable melanoma must have received prior anti-PD-(L)1 for ≥ 6 weeks and experienced disease progression while still on active adjuvant therapy containing anti-PD-(L)1, or participant who had early relapse occurring \< 24 weeks after end of adjuvant anti-PD-(L)1 therapy. Progressive disease must be ascertained by confirmatory biopsy collected at baseline.
• Participant whose unresectable/metastatic disease progressed while on or within \< 24 weeks of completion of anti-PD-(L)1 for inresectable/metastatic melanoma. Progressive disease must have been confirmed by imaging ≥ 4 weeks after evidence of initial disease progression.
• Participant must have received no more than 2 prior lines of therapy for melanoma and at least one prior regimen must have contained anti-PD-(L)1 therapy (alone or as part of a combination) either in the adjuvant and/or advanced/metastatic setting.
• Participants must have had known BRAF V600 mutation status per local institutional testing standards.
• Participants must have fresh biopsy available after completing prior PD-(L)1 therapy or be willing and able to safely undergo pretreatment tumor biopsies (core or excisional). Determination of whether participants can safely undergo biopsy should be made by the treating physician in consultation with the individual performing the biopsy.
• Participant must have at least 1 measurable tumor lesion per RECIST v1.1.
• Phase 2, Cohort B:
• Participant with previously untreated, histologically confirmed Stage III (unresectable) or IV melanoma per the American Joint Committee on Cancer v8 staging system.
• Participants must not have had prior systemic anticancer therapy for unresectable or metastatic melanoma.
• Participants must have had known BRAF V600 mutation status per local institutional testing standards.
• Participants must have fresh biopsy available or be willing and able to safely undergo pretreatment tumor biopsies (core or excisional). Determination of whether participants can safely undergo biopsy should be made by the treating physician in consultation with the individual performing the biopsy.
• Phase 2 (Cohorts A and B): Participant must have at least 1 measurable tumor lesion per RECIST v1.1.

You may not qualify if:

• 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.
• Participant who had prior treatment with a LAG-3 or TIM-3 targeted agent.
• Phase 1: (Parts 1-4):
• Receipt of anticancer medications or investigational drugs within the following intervals before the first administration of study treatment:
• ≤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.
• Administration of colony-stimulating factors (including granulocyte colony-stimulating factor, granulocyte macrophage colony-stimulating factor, or recombinant erythropoietin) within 14 days before study Day 1.
• Phase 2:
• Cohort A: Participant who has discontinued anti-PD-(L)1 therapy due to toxicity or other reasons unrelated to toxicity, then subsequently experienced disease progression.
• Cohort A: Participant who had experienced objective response (PR/CR) and had stopped anti-PD-(L)1 therapy due to maximal benefit.
• Cohort A: Participant with multiple metastases that achieved mixed tumor response to prior anti-PD-(L)1 therapy (such as isolated progressive lesion in a context of PR/CR or SD for other lesions) or achieved overall disease progression based only on a single new lesion.
• Cohort B: Participant who has or has had uveal melanoma.
• Receipt of anticancer therapy (immunotherapy, chemotherapy, targeted therapy or hormonal therapy) within 21 days of the first administration of study treatment, with the exception of localized radiotherapy.
• Palliative radiation therapy administered within 1 week of first dose of study treatment or radiation therapy in the thoracic region that is \> 30 Gy within 6 months of the first dose of study treatment.
• If participant received major surgery, then they must have recovered adequately from toxicities and/or complications from the intervention before starting study treatment.

Sponsors & Collaborators

• Incyte Corporation: lead

Study Sites (17)

The Angeles Clinic and Research Institute

Los Angeles, California, 90025, United States

Location

University of Miami Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

H Lee Moffitt Cancer Center and Research

Tampa, Florida, 33612, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

Cancer Center For Blood Disorders A Division of American Oncology Partners P.A

Bethesda, Maryland, 20817, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

John Theurer Cancer Center, Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Nyu Langone Laura and Isaac Perlmutter Cancer Center

New York, New York, 10016, United States

Location

Carolina Bio Oncology

Huntersville, North Carolina, 28078, United States

Location

Penn State Hershey Cancer Institute

Hershey, Pennsylvania, 17033, United States

Location

Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

University of Washington-Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

Melanoma Institute Australia

Wollstonecraft, New South Wales, 02060, Australia

Location

Greenslopes Private Hospital

Brisbane, Queensland, Australia

Location

Flinders Medical Centre

Bedford Park, South Australia, 05042, Australia

Location

Box Hill Hospital

Box Hill, Victoria, 03128, Australia

Location

One Clinical Research

Nedlands, Western Australia, 06009, Australia

Location

MeSH Terms

Conditions

Melanoma

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: April 29, 2020
• First Posted: May 1, 2020
• Study Start: July 27, 2020
• Primary Completion: August 25, 2025
• Study Completion: August 25, 2025
• Last Updated: October 3, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data will be shared after the primary publication or 2 years after the study has ended for market authorized products and indications.
• Access Criteria: Data from eligible studies will be shared with qualified researchers according to the criteria and process described in the Data Sharing section of the www.incyteclinicaltrials.com website. For approved requests, the researchers will be granted access to anonymized data under the terms of a data sharing agreement.

Locations

US (12); AU (5)