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

• Status: Recruiting
• Trial end date: 2023-09-22
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Incyte Corporation

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%