INCB106385 Alone or in Combination With Immunotherapy in Advanced Solid Tumors

This is a multicenter, open-label, dose-escalation/dose-expansion Phase 1 clinical study to investigate the safety, tolerability, PK profile, pharmacodynamics, and preliminary clinical efficacy of INCB106385 when given as monotherapy or in combination with INCMGA00012 in participants with selected CD8 T-cell-positive advanced solid tumors including SCCHN, NSCLC, ovarian cancer, CRPC, TNBC, bladder cancer, and specified GI malignancies (defined as CRC, gastric/GEJ cancer, HCC, PDAC, or SCAC)


Eligibility Criteria:
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, ovarian cancer, TNBC, CRPC, bladder cancer, and specified GI malignancies (defined as CRC, gastric/GEJ cancer, HCC, PDAC, or SCAC) that progressed after treatment with available 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 treatment in the past 2 years or receiving systemic therapy for an autoimmune or inflammatory disease..
* Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (doses \> 10 mg daily of prednisone or equivalent) or any other form of immunosuppressive therapy within 7 days before the first dose of study treatment.
* Known additional malignancy that is progressing or requires active treatment,or history 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/or complications from prior surgical intervention before starting study treatment.
* Evidence of interstitial lung disease, history of interstitial lung disease, or active, noninfectious pneumonitis.
* Immune-related toxicity during prior immune therapy for which permanent discontinuation of therapy is recommended, or any immune-related toxicity requiring intensive or prolonged immunosuppression to manage.
* Any prior chemotherapy, biological therapy, or targeted therapy to treat the participant's disease within 5 half-lives or 28 days (whichever is shorter) before the 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 treated with an investigational medication within 5 half-lives or 28 days (whichever is shorter) 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 week of 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) or formulation components.
* Presence of a gastrointestinal condition that may affect drug absorption.
* Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study.
* Any condition that would, in the investigator's judgment, interfere with full participation in the study,pose a significant risk to the participant; or interfere with interpretation of study data