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

• ClinicalTrials.gov Identifier: NCT04370704
• Recruitment Status: Recruiting
• First Posted: May 1, 2020
• Last Update Posted: December 19, 2020
• Sponsor: Incyte Corporation
• Information provided by (Responsible Party): Incyte Corporation

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Melanoma	Drug: INCAGN02385; Drug: INCAGN02390; Drug: INCMGA00012.	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 52 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: July 28, 2020
• Estimated Primary Completion Date: July 26, 2023
• Estimated Study Completion Date: July 26, 2023

Arms and Interventions

Arm	Intervention/treatment
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.	Drug: INCAGN02385; INCAGN02385 administered intravenously; Drug: INCAGN02390; INCAGN02390 administered intravenously
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.	Drug: INCAGN02385; INCAGN02385 administered intravenously; Drug: INCAGN02390; INCAGN02390 administered intravenously; Drug: INCMGA00012.; INCMGA00012 administered intravenously
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	Drug: INCAGN02385; INCAGN02385 administered intravenously; Drug: INCAGN02390; INCAGN02390 administered intravenously; Drug: INCMGA00012.; INCMGA00012 administered intravenously

Outcome Measures

Primary Outcome Measures :

1. 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
2. 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.
3. 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.
4. 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

Secondary Outcome Measures :

1. 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.
2. 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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%

Contacts and Locations

Contacts

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

Locations

United States, California

The Angeles Clinic and Research Institute; Recruiting

Los Angeles, California, United States, 90025

United States, New Jersey

John Theurer Cancer Center, Hackensack University Medical Center; Recruiting

Hackensack, New Jersey, United States, 07601

United States, North Carolina

Carolina Bio Oncology; Recruiting

Huntersville, North Carolina, United States, 28078

United States, Pennsylvania

Hillman Cancer Center; Recruiting

Pittsburgh, Pennsylvania, United States, 15232

Sponsors and Collaborators

Incyte Corporation

More Information

• Responsible Party: Incyte Corporation
• ClinicalTrials.gov Identifier: NCT04370704
• Other Study ID Numbers: INCAGN 2385-201
• First Posted: May 1, 2020
• Last Update Posted: December 19, 2020
• Last Verified: December 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Incyte Corporation:

PD-1 Inhibitors; INCAGN02385; INCAGN02390; INCMGA00012

Additional relevant MeSH terms:

Melanoma; Neoplasms; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas