Locally Advanced or Metastatic Solid Tumors
Conditions
Interventions
S-531011 ( intravenous infusion)
Sponsors
Gomez Juan Carlos
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion 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), nonsmall 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). Participants with colorectal cancer (CRC), pancreatic cancer (PC), cervical cancer (CC), epithelial ovarian cancer (epOC), 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. 5. (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 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. 6. (Part C 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-EGFR therapy if RAS (KRAS/NRAS) wild-type and medically appropriate; 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. 7. (Parts D and E) 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-EGFR therapy if RAS (KRAS/NRAS) wild-type and medically appropriate; 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
Exclusion criteria
Exclusion criteria: 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 diseasemodifying 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 antiinfectives 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 (participants with positive HCV antibody are eligible if a confirmatory HCV RNA test is undetectable). 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.(Parts D and E only) Serious non-healing wound, non-healing ulcer, or non-healing bone fracture. 12.(Parts D and E only) Presence or history of severe arterial thromboembolic events (eg, cerebral infarction, transient ischemic attacks, myocardial infarction, and angina) within 6 months prior to the first dose of study intervention, and/or >= Grade 3 venous thromboembolic events (eg, deep vein thrombosis) within 3 months prior to the first dose of study intervention. Participants who receive a full-dose therapeutic anticoagulation should be excluded. 13.(Parts D and E only) Known coagulopathy that increases risk of bleeding, bleeding diatheses, or any other hemorrhage/bleeding event of >= Grade 3 within 4 weeks prior to the first dose of study intervention. 14.(Parts D and E only) Presence or history of any life-threatening vascular endothelial growth factor (VEGF)-related adverse event. 15.(Parts D and E only) Proteinuria >= 2+ by urine dipstick test within 4 weeks prior to the first dose of study intervention. 16. Clinical evidence of uncontrolled brain metastasis. 17. Clinically uncontrollable symptomatic pleural effusion and/or ascites. (Participants who do not require fluid drainage or have no significant increase of fluid for 28 days may be eligible with approval by the sponsor.) 18. Known additional malignancy that is progressing or has required active treatment within the past 3 years. 19. (Parts B, C, D and E CRC cohorts only): Colorectal cancer with mismatch repair deficient/microsatellite instability-high status. 20. (Parts A-2, C and E only):Has received prior therapy with an anti-programmed cell death 1, anti-programmed cell death ligand 1, or anti-programmed cell death ligand 2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, cytotoxic T-lymphocyte-associated protein 4, OX-40, CD137), and was discontinued from that treatment due to >= Grade 3 immune-related adverse event. 21. Prior treatment with systemic anticancer drugs (including any investigational medicinal products) with
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Part A: Number of Participants with Treatment-emergent Adverse Events (TEAEs) [Time Frame: Part A-1, Approximately 12 months; Part A-2; Approximately 24 months] 2. Parts B, C, D and E: Objective Response Rate [Time Frame: Every 6 weeks for the first 24 weeks and every 9 weeks thereafter, until disease progression (Part B, Approximately 12 months; Part C, D and E, Approximately 24 months)] 3. Parts B, C, D and E: Duration of Response [Time Frame: Every 6 weeks for the first 24 weeks and every 9 weeks thereafter, until disease progression (Part B, Approximately 12 months; Part C, D and E, Approximately 24 months)] 4. Parts B, C, D and E: Disease Control Rate [Time Frame: Every 6 weeks for the first 24 weeks and every 9 weeks thereafter, until disease progression (Part B, Approximately 12 months; Part C, D and E, Approximately 24 months)] 5. Parts B, C, D and E: Time to Response [Time Frame: Every 6 weeks for the first 24 weeks and every 9 weeks thereafter, until disease progression (Part B, Approximately 12 months; Part C, D and E, Approximately 24 months)] 6. Parts B, C, D and E: Progression-free Survival [Time Frame: Every 6 weeks for the first 24 weeks and every 9 weeks thereafter, until disease progression (Part B, Approximately 12 months; Part C, D and E, Approximately 24 months)] 7. Parts B, C, D and E: Overall Survival [Time Frame: From first dose to death, or up to a maximum of 18 months after last dose in the last participant] | — |
Countries
Japan, Part A: USA, Part B C: Asia, North America, EU, Part D E: USA
Contacts
Public ContactCorporate Communications Department
Shionogi & Co., Ltd.
Outcome results
None listed