A Study of DS5361b in Participants With Advanced Solid Tumors

Key Inclusion Criteria:

The clinical site will screen for the full inclusion criteria per protocol.

• Adults ≥18 years of age at the time the ICF is signed (Please follow local regulatory requirements if the legal age of consent for trial participation is >18 years old).
• Has histologically- or cytologically documented recurrent, metastatic, or unresectable solid tumors that are refractory to or intolerable with standard treatment or for which no standard treatment is available (For Part 1 and Part 2 only).
• Participants need to have documented TMB or MSI status using a validated or approved genomic test as per applicable regulations prior to Cycle 1 Day 1. In Part 1 and Part 2, participants need to have documented TMB-H and/or MSI-H status. In Part 3, participants need to have documented TMB-H status.
• Has measurable disease based on local CT/MRI imaging as assessment by the investigator using RECIST v1.1.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.
• Has adequate organ and bone marrow function as assessed by local laboratory within 14 days prior to initiation of trial intervention.
• For HNSCC participants only: have documented results from local testing of HPV for oropharyngeal cancer. If HPV status has previously been tested using this procedure, no retesting is required.

Dose Expansion (Part 3) Only:

• Has histologically or cytologically confirmed, Stage IV NSCLC without actionable gene alteration.

• No prior systemic therapy.
• Participants with PD-L1 TPS ≥1%.
• Has histologically or cytologically confirmed recurrent or metastatic HNSCC that is considered incurable by local therapies.

• No prior systemic therapy administered in the recurrent or metastatic setting.
• Participants with PD-L1 CPS ≥1.

Key Exclusion Criteria:

• Has spinal cord compression or clinically active central nervous system metastases.
• Has a history of leptomeningeal carcinomatosis.
• Uncontrolled or significant cardiovascular disease.
• Any of the following within the past 6 months prior to enrollment: cerebrovascular accident, transient ischemic attack, or other arterial thromboembolic event.
• Has a history of (noninfectious) interstitial lung disease (ILD)/pneumonitis that required corticosteroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out.
• Clinically severe pulmonary compromise (ie, requiring any supplemental oxygen).
• Has any evidence of severe or uncontrolled systemic diseases.
• Has active or uncontrolled HBV infection. Hepatitis B SCR testing is required.
• Has active or uncontrolled HCV infection. Hepatitis C SCR testing is required.
• For the dose escalation phase (Part 1 and Part 2), has HIV infection. For the dose expansion part (Part 3), has active or uncontrolled HIV infection.
• Prior organ transplantation, including allogeneic stem cell transplantation.
• Has an active, known, or suspected autoimmune disease.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 14 days prior to the trial intervention.