This is an open-label, Phase 1b, platform study in subjects with advanced or metastatic solid tumors. The study will be divided into 3 parts (Part 1a, Part 1b, and Part 2). Part 1a will evaluate a JAK inhibitor with JAK1 selectivity (Itacitinib) in combination with an IDO1 inhibitor (epacadostat; INCB024360; Group A) and Itacitinib in combination with a PI3K-delta inhibitor (INCB050465; Group B) to determine the MTD or PAD and the recommended Part 1b doses for each combination. Once the recommended dose has been identified for each treatment group in Part 1a, subjects with advanced solid tumors will be enrolled into expansion cohorts based upon prior treatment history with a PD-1 pathway-targeted agent (Part 1b). In Part 2, additional expansion cohorts will be enrolled to further evaluate lower doses of itacitinib and INCB050465 in subjects with select tumor types.

Inclusion Criteria:

• Male or female, age 18 years or older.
• Willingness to provide written informed consent for the study.
• Part 1a: Subjects with histologically or cytologically confirmed advanced or metastatic solid tumors that have failed prior standard therapy (including subject refusal or intolerance).
• Part 1b: Subjects with endometrial cancer, gastric cancer, head and neck squamous cell carcinoma, melanoma, microsatellite unstable colorectal cancer, non-small cell lung cancer, pancreatic ductal adenocarcinoma, renal cell carcinoma, triple negative breast cancer, or transitional cell carcinoma of the genitourinary tract that have had disease progression after available therapies for metastatic disease that are known to confer clinical benefit, been intolerant to treatment, or refused standard treatment.
• Part 1b: Must have documented confirmed disease progression on a prior programmed cell death-1 (PD-1) pathway targeted agent or must be PD-1 pathway-targeted treatment naïve.
• Part 2: Subjects with HNSCC, NSCLC, pancreatic ductal adenocarcinoma, salivary gland cancer, and transitional cell carcinoma of the genitourinary tract that have had disease progression after available therapies for advanced or metastatic disease that are known to confer clinical benefit, have been intolerant to treatment, or have refused standard treatment.
• Willingness to undergo a pre-treatment and on-treatment tumor biopsy to obtain the specimen.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

Exclusion Criteria:

• Laboratory parameters not within the protocol-defined range.
• Receipt of anticancer medications or investigational drugs within a defined interval before the first administration of study drug.
• Received an immune-suppressive based treatment for any reason within 14 days prior to the first dose of study treatment.
• Has not recovered from toxic effect of prior therapy to < Grade 1.
• Active or inactive autoimmune process.
• Has received a live vaccine within 30 days of planned start of study therapy.
• Active infection requiring systemic therapy.