S-531011 as Monotherapy and in Combination With an Immune Checkpoint Inhibitor in Advanced or Metastatic Solid Tumors

Eligibility Criteria

• 1. Male or female participant must be at least 18 years of age inclusive (or complies with country-specific regulatory requirements), at the time of signing the informed consent.
• 2. Participants with histologically or cytologically confirmed advanced (locoregionally recurrent, not amenable to curative therapy) or metastatic solid tumors who have no standard therapies with a proven clinical benefit, or who are intolerant to or unwilling to receive these therapies for any reasons.
• 3. Measurable disease by RECIST 1.1.
• 4. (Part A only) Participants should have 1 of the following tumor types: malignant melanoma (MEL), head and neck squamous cell carcinoma (HNSCC), renal cell carcinoma (RCC), urothelial carcinoma (UC), non-small cell lung cancer (NSCLC), or triple-negative breast cancer (TNBC), esophageal cancer (EC; esophageal squamous cell carcinoma and adenocarcinoma), or gastric cancer (GC; gastric and gastroesophageal junction adenocarcinoma).
• 5. (Part B only) Participants should have 1 of specific histologically or cytologically confirmed tumor types selected by the sponsor after the determination of tentative RP2D(s) in Part A-1.
• 6. (Part C only) Participants should have 1 of specific histologically or cytologically confirmed tumor types selected by the sponsor after the determination of tentative RP2D(s) in Part A-2.
• 7. Participants should be willing and able to provide permission to access archival formalin-fixed paraffin-embedded (FFPE) tumor tissues (as block or unstained slides) for this study.
• 8. Participants should be willing and able to provide both pre-treatment and on-treatment paired tumor biopsy samples.
• 9. (At selected sites only) Participants should be willing and able to provide both pre-treatment and on-treatment paired tumor biopsy samples. Fresh tissue samples are required as these will be used for the proof of mechanism analysis.
• 10. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.
• 11. An estimated life expectancy of at least 12 weeks.
• 12. Adequate hematologic and organ function as confirmed by laboratory values.
• 13. QT interval corrected with the Fridericia formula (QTcF) ≤ 480 milliseconds in 12-lead electrocardiogram (ECG) at Screening.
• 1. Presence or history of autoimmune diseases or immune-mediated diseases that require chronic use of systemic corticosteroids (\> 10 mg of prednisone equivalent per day), immunosuppressive agents, or disease-modifying agents.
• 2. Presence or history of interstitial lung disease and (non-infectious) pneumonitis that required corticosteroids.
• 3. Active clinically significant bacterial, viral or fungal infection, or any major episode of infection requiring hospitalization or treatment with parenteral anti-infectives within 4 weeks before the first dose of study intervention.
• 4. Uncontrolled or clinically significant cardiovascular disease defined as New York Heart Association (NYHA) classification III or IV.
• 5. A positive test for hepatitis B surface antigen (HBsAg) and/or hepatitis C virus (HCV) antibody (a confirmatory HCV RNA test if HCV antibody was positive).
• 6. A positive serological test for human immunodeficiency virus (HIV) infection.
• 7. Known history of any other relevant congenital or acquired immunodeficiency.
• 8. Known history of an allogeneic tissue and/or solid organ transplant.
• 9. Known history of severe allergy, hypersensitivity, anaphylaxis, or any serious adverse reaction to any component of study intervention or formulation components and/or any other monoclonal antibodies.
• 10. Women who are pregnant or breastfeeding or trying to become pregnant.
• 11. Clinical evidence of uncontrolled brain metastasis.
• 12. Known additional malignancy that is progressing or has required active treatment within the past 3 years.
• 13. (Parts A-2 and C only): Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137), and was discontinued from that treatment due to ≥ Grade 3 immune-related adverse event (irAE).
• 14. Prior treatment with systemic anticancer drugs (including any investigational medicinal products) within 28 days or 5 half-lives (whichever is shorter) before the first dose of study intervention.
• 15. Prior major surgery within 28 days before the first dose of study intervention.
• 16. Prior extended field radiotherapy within 28 days before the first dose of study intervention (within 14 days for limited field radiation for palliation) or history of radiation pneumonitis.
• 17. Participants who have not recovered from any previous treatment toxicities to ≤ Grade 1 or baseline (except alopecia and peripheral neuropathy) before the first dose of study intervention.
• 18. Prior treatment with anti-CCR8 antibody for any indication.
• 19. Receipt of hematopoietic growth factors (eg, granulocyte-colony stimulating factor \[G-CSF\] or erythropoietin) within 14 days before the first dose of study intervention or blood transfusions within 14 days before the first dose of study intervention.
• 20. Receipt of a live, attenuated vaccine within 30 days before the first dose of study intervention.