INCB106385 Alone or in Combination With Immunotherapy in Advanced Solid Tumors

Inclusion Criteria:

• Ability to comprehend and willingness to sign an ICF.

• Willing and able to conform to and comply with all Protocol requirements.

• Histologically or cytologically confirmed advanced/metastatic SCCHN, NSCLC, ovariancancer, TNBC, CRPC, bladder cancer, and specified GI malignancies (defined as CRC,gastric/GEJ cancer, HCC, PDAC, or SCAC) that progressed after treatment withavailable therapies (including anti PD-(L)1 therapy (if applicable).

• Willingness to undergo pre- and on-treatment tumor biopsy.

• Have CD8 T-cell-positive tumors.

• Presence of measurable disease according to RECIST v1.1.

• ECOG performance status 0 to 1.

• Life expectancy > 12 weeks.

• Willingness to avoid pregnancy or fathering children based.

• Acceptable laboratory parameters

Exclusion Criteria:

• Clinically significant cardiac disease.

• Known or active CNS metastases and/or carcinomatous meningitis.

• Active or inactive autoimmune disease or syndrome that required systemic treatmentin the past 2 years or receiving systemic therapy for an autoimmune or inflammatorydisease..

• Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (doses > 10 mg daily of prednisone or equivalent) or any other form ofimmunosuppressive therapy within 7 days before the first dose of study treatment.

• Known additional malignancy that is progressing or requires active treatment,orhistory of other malignancy within 2 years of the first dose of study treatment.

• Has not recovered to ≤ Grade 1 from toxic effects of prior therapy and/orcomplications from prior surgical intervention before starting study treatment.

• Evidence of interstitial lung disease, history of interstitial lung disease, oractive, noninfectious pneumonitis.

• Immune-related toxicity during prior immune therapy for which permanentdiscontinuation of therapy is recommended, or any immune-related toxicity requiringintensive or prolonged immunosuppression to manage.

• Any prior chemotherapy, biological therapy, or targeted therapy to treat theparticipant's disease within 5 half-lives or 28 days (whichever is shorter) beforethe first dose of study treatment.

• Any prior radiation therapy within 28 days before the first dose of study treatment.

• Undergoing treatment with another investigational medication or having been treatedwith an investigational medication within 5 half-lives or 28 days (whichever isshorter) before the first dose of study treatment.

• Concomitant treatment with strong CYP3A4 inhibitors or inducers.

• Receipt of a live vaccine within 30 days of the first dose of study treatment.

• Infection requiring parenteral antibiotics, antivirals, or antifungals within 1 weekof the first dose of study treatment.

• Evidence of HBV or HCV infection or risk of reactivation.

• Known history of HIV (HIV 1/2 antibodies).

• History of organ transplant, including allogeneic stem-cell transplantation.

• Known hypersensitivity or severe reaction to any component of study drug(s) orformulation components.

• Presence of a gastrointestinal condition that may affect drug absorption.

• Is pregnant or breastfeeding or expecting to conceive or father children within theprojected duration of the study.

• Any condition that would, in the investigator's judgment, interfere with fullparticipation in the study,pose a significant risk to the participant; or interferewith interpretation of study data