The purpose of this study is to determine the safety, tolerability, and preliminary efficacy of INCAGN02385 in participants with advanced malignancies.

Inclusion Criteria:

• Locally advanced or metastatic disease; locally advanced disease must not be amenable to resection with curative intent.
• Disease progression after treatment with available therapies that are known to confer clinical benefit, or intolerant to treatment, or refuse noncurative standard treatment. There is no limit to the number of prior treatment regimens.
• Participants with advanced or metastatic cervical cancer, MSI-high endometrial cancer, gastric cancer (including stomach and GEJ), esophageal cancer, hepatocellular carcinoma, melanoma (uveal melanoma excluded), Merkel cell carcinoma, mesothelioma, MSI-high colorectal cancer, NSCLC, ovarian cancer, SCCHN, SCLC, RCC, triple-negative breast cancer, and urothelial carcinoma, or alternative immunogenic tumor types with medical monitor approval. Participants with DLBCL may participate in Part 2 of the study.
• Presence of measureable disease based on RECIST v1.1 for solid tumors or the Lugano classification for DLBCL.
• Willingness and ability to safely undergo pretreatment and on-treatment tumor biopsies.
• Eastern Cooperative Oncology Group performance status 0 or 1.

Exclusion Criteria:

• Laboratory and medical history parameters outside the protocol-defined range.
• Transfusion of blood products (including platelets or red blood cells) or 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.
• Receipt of anticancer medications or investigational drugs within protocol-defined intervals before the first administration of study drug.
• Receipt of a live vaccine within 30 days of planned start of study drug.
• Active autoimmune disease that required systemic treatment in the past.
• Known active CNS metastases and/or carcinomatous meningitis.
• Known additional malignancy that is progressing or requires active treatment, or history of other malignancy within 2 years of study entry. See protocol-defined exceptions.
• Evidence of active, noninfectious pneumonitis or history of interstitial lung disease.
• Active infection requiring systemic therapy.
• Evidence of hepatitis B virus or hepatitis C virus infection or risk of reactivation.
• Known history of HIV (HIV 1/2 antibodies).
• Prior treatment with an anti-LAG-3 antibody for any indication.