To evaluate the safety, tolerability, and DLTs and determine the MTD and/or RDE(s) of INCA33890 in participants with select advanced or metastatic solid tumors.

Inclusion Criteria:

• ≥18 years old
• Histologically or cytologically confirmed advanced or metastatic malignancies as defined in the protocol.
• Part 1: Participants must have experienced disease progression after treatment with, be intolerant to, or be ineligible for, or refused available therapies, including anti-PD-(L)1 or anti-CTLA4 therapy if applicable, that are known to confer clinical benefit. Part 2: depending on cohort, participants may have received or not prior treatment for the malignancy under study.
• ECOG performance status score of 0 or 1.
• Willingness to undergo pre- and on-treatment tumor biopsy (core or excisional). Biopsies are mandatory depending on the cohorts.
• Presence of measurable disease according to RECIST v1.1.

Exclusion Criteria:

• Any known additional malignancy that is progressing or requires active treatment, or history of other malignancy within 2 years.

• Not recovered to ≤ Grade 1 or baseline from residual toxicities of prior therapy.

• Has active autoimmune disease requiring systemic immunosuppression with corticosteroids.

• Brain or CNS metastases untreated or that have progressed.

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

• History of clinically significant or uncontrolled cardiac disease.

• Active HBV, active HCV, or HIV positive.

• Is on chronic systemic steroids (> 10 mg/day of prednisone or equivalent).

• Chronic or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment

• Participants that have been initiated on or had modifications in anticoagulation therapies within the last 3 months prior to first dose of treatment.

• Significant concurrent, uncontrolled medical condition, eg:

  • Cardiovascular: Participants with known vasculitis, aneurisms, and other vascular malformations of clinical significance or history of myocarditis.
  • Gastrointestinal: Any bowel obstruction within 60 days prior to C1D1.

• Participants with adequate laboratory values within the protocol defined ranges.

Other protocol-defined Inclusion/Exclusion Criteria may apply.

Incyte shares data with qualified external researchers after a research proposal is submitted. These requests are reviewed and approved by a review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

The trial data availability is according to the criteria and process described on https://www.incyte.com/our-company/compliance-and-transparency

Data will be shared after the primary publication or 2 years after the study has ended for market authorized products and indications.

Data from eligible studies will be shared with qualified researchers according to the criteria and process described in the Data Sharing section of the www.incyteclinicaltrials.com website. For approved requests, the researchers will be granted access to anonymized data under the terms of a data sharing agreement.