The purpose of this study is to evaluate the safety and tolerability, pharmacokinetics, pharmacodynamics, and early clinical activity of INCB086550 in participants with advanced solid tumors who have failed prior treatments.

Inclusion Criteria:

• Histologically confirmed advanced solid tumors with measurable lesions per RECIST v1.1 or RANO for primary brain tumors that are considered nonamenable to surgery or other curative treatments or procedures. Tumor lesions located in a previously irradiated area, or in an area subjected to other loco-regional therapy, are considered measurable per RECIST v1.1 if progression has been demonstrated in the lesion.
• Willingness to undergo a tumor biopsy to obtain tumor tissue,Pretreatment and on-treatment tumor biopsies are required.
• Must have disease progression after treatment with available therapies that are known to confer clinical benefit or who are intolerant to or ineligible for standard treatment. There is no limit to the number of prior treatment regimens.
• Eastern Cooperative Oncology Group performance status score of 0 or 1.
• Life expectancy > 12 weeks.
• Willingness to avoid pregnancy or fathering children.
• Part 2 Expansion Cohort 2-A only: Participants with any type of solid tumor that has a local regulatory approval for an anti-PD-1 therapy. Other tumor types may be enrolled with medical monitor approval. Participants must have had confirmed disease progression on a prior anti-PD-1 monoclonal antibody.
• Part 2 Expansion Cohort 2-B only: Participants with select solid tumors who are immunotherapy-naïve.
• Part 3 MSI-H or dMMR Expansion Cohort only (Enrolled ex-United States only): Participants with any MSI-H or dMMR solid tumor who are immunotherapy-naïve.
• Part 4 HPV-driven expansion cohort only: Participants with any HPV-positive solid tumor who have received prior standard therapy.

Note: HPV-positive status determined by a local laboratory using p16 IHC, polymerase chain reaction methods, or other locally-available method to detect HPV

Exclusion Criteria:

• Laboratory values not within the Protocol-defined range.
• Clinically significant cardiac disease.
• History or presence of an ECG that, in the investigator's opinion, is clinically meaningful.
• Untreated brain or central nervous system (CNS) metastases or brain or CNS metastases that have progressed. Participants who have previously treated and clinically stable brain or CNS metastases and have not required steroids for at least 7 days before study treatment are eligible.
• Known additional malignancy that is progressing or requires active treatment.
• Has not recovered to ≤ Grade 1 or baseline from toxic effects of prior therapy and/or complications from prior surgical intervention before starting study treatment.
• Treatment with anticancer medications or investigational drugs within protocol-defined intervals before the first administration of study drug.
• Active infection requiring systemic therapy.
• Active HBV or HCV infection that requires treatment.
• Known history of HIV (HIV 1/2 antibodies).
• Known hypersensitivity or severe reaction to any component of study drug or formulation components.
• Prior receipt of an anti-PD-L1 therapy for all participants.
• Presence of a gastrointestinal condition that may affect drug absorption.