The primary objective of Part A is to evaluate the safety and tolerability of S-531011 and to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of S-531011 with or without pembrolizumab.
The primary objective of Parts B and C is to evaluate the antitumor activity of S-531011 at the RP2D with or without pembrolizumab.
The primary objective of Parts D and E is to evaluate the antitumor activity of S-531011 at the RP2D in combination with bevacizumab with our without pembrolizumab.
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.
Measurable disease by Response Evaluation Criteria in Solid Tumors version 1.1.
(Part A only) Participants should have 1 of the following tumor types: malignant melanoma, head and neck squamous cell carcinoma, renal cell carcinoma, urothelial carcinoma, non-small cell lung cancer, or triple-negative breast cancer, esophageal cancer (esophageal squamous cell carcinoma and adenocarcinoma), or gastric cancer (gastric and gastroesophageal junction adenocarcinoma). Participants with colorectal cancer (CRC), pancreatic cancer, cervical cancer, epithelial ovarian cancer, and other types of solid tumors may also be enrolled upon discussion with and approval by the sponsor. For the backfill cohorts only, specific tumor types may be selected.
(Part B CRC cohorts only) Participants must have histologically or cytologically confirmed metastatic adenocarcinoma of the colon or rectum, who had disease progression on or after receiving all of the following standard of care systemic therapies for advanced or metastatic disease or who were intolerant to: fluoropyrimidine, oxaliplatin, and irinotecan; anti-epidermal growth factor receptor (EGFR) therapy if rat sarcoma virus (RAS) (Kirsten RAS/neuroblastoma RAS [KRAS/NRAS]) wild-type and medically appropriate ; V-raf murine sarcoma viral oncogene homolog B (BRAF) inhibitor if BRAF V600E mutation. In addition, participants who received up to 2 additional lines of therapy for advanced or metastatic disease of the following therapies are also eligible: trifluridine/tipiracil, regorafenib, fruquintinib, other drugs approved in the country, or investigational drugs.
Presence or history of autoimmune diseases or immune-mediated diseases that require chronic use of systemic corticosteroids (> 10 milligrams of prednisone equivalent per day), immunosuppressive agents, or disease-modifying agents.
Presence or history of interstitial lung disease and (non-infectious) pneumonitis that required corticosteroids.
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.
Uncontrolled or clinically significant cardiovascular disease defined as New York Heart Association classification III or IV.
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Treatment groupsSee each treatment group below.
Shionogi
Lead sponsor
Merck Sharp & Dohme LLC
Collaborator