S-531011 as Monotherapy and in Combination With an Immune Checkpoint Inhibitor in Advanced or Metastatic Solid Tumors
- Registration Number
- NCT05101070
- Lead Sponsor
- Shionogi
- Brief Summary
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.
The primary objective of Parts B and C is to evaluate the antitumor activity of S-531011 at the RP2D.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 274
Inclusion Criteria
- 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.
- 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 RECIST 1.1.
- (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).
- (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.
- (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.
- 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.
- Participants should be willing and able to provide both pre-treatment and on-treatment paired tumor biopsy samples.
- (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.
- Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.
- An estimated life expectancy of at least 12 weeks.
- Adequate hematologic and organ function as confirmed by laboratory values.
- QT interval corrected with the Fridericia formula (QTcF) ≤ 480 milliseconds in 12-lead electrocardiogram (ECG) at Screening.
Exclusion Criteria
- 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.
- 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 (NYHA) classification III or IV.
- 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).
- A positive serological test for human immunodeficiency virus (HIV) infection.
- Known history of any other relevant congenital or acquired immunodeficiency.
- Known history of an allogeneic tissue and/or solid organ transplant.
- 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.
- Women who are pregnant or breastfeeding or trying to become pregnant.
- Clinical evidence of uncontrolled brain metastasis.
- Known additional malignancy that is progressing or has required active treatment within the past 3 years.
- (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).
- 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.
- Prior major surgery within 28 days before the first dose of study intervention.
- 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.
- 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.
- Prior treatment with anti-CCR8 antibody for any indication.
- 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.
- Receipt of a live, attenuated vaccine within 30 days before the first dose of study intervention.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part B: S-531011 Monotherapy S-531011 Participants will receive S-531011 at the the RP2D by intravenous infusion for up to approximately 12 months. Part A-1: S-531011 Monotherapy S-531011 Participants will receive escalating doses of S-531011 by intravenous infusion for up to approximately 12 months. Part A-2: S-531011 + pembrolizumab pembrolizumab Participants will receive escalating doses of S-531011 in combination with pembrolizumab by intravenous infusion for up to approximately 12 months. Part C: S-531011 + pembrolizumab S-531011 Participants will receive S-531011 at the RP2D in combination with pembrolizumab by intravenous infusion for up to approximately 12 months. Part C: S-531011 + pembrolizumab pembrolizumab Participants will receive S-531011 at the RP2D in combination with pembrolizumab by intravenous infusion for up to approximately 12 months. Part A-2: S-531011 + pembrolizumab S-531011 Participants will receive escalating doses of S-531011 in combination with pembrolizumab by intravenous infusion for up to approximately 12 months.
- Primary Outcome Measures
Name Time Method Parts B and C: Overall Survival From first dose up to a maximum of 18 months after last dose; 2.5 years Parts B and C: Objective Response Rate Every 6 weeks for the first 24 weeks and every 9 weeks thereafter, until the end of treatment (approximately 12 months). Parts B and C: Time to Response Every 6 weeks for the first 24 weeks and every 9 weeks thereafter, until the end of treatment (approximately 12 months). Part A: Number of Participants with Treatment-emergent Adverse Events (TEAEs) Approximately 12 months Parts B and C: Duration of Response From first dose up to a maximum of 18 months after last dose; 2.5 years Parts B and C: Disease Control Rate Every 6 weeks for the first 24 weeks and every 9 weeks thereafter, until the end of treatment (approximately 12 months). Parts B and C: Progression-free Survival From first dose up to a maximum of 18 months after last dose; 2.5 years
- Secondary Outcome Measures
Name Time Method Part A: Disease Control Rate Every 6 weeks for the first 24 weeks and every 9 weeks thereafter, until the end of treatment (approximately 12 months). Part A: Time to Response Every 6 weeks for the first 24 weeks and every 9 weeks thereafter, until the end of treatment (approximately 12 months). Part A: Terminal elimination rate constant (λz) of S-531011 Cycle 1, Day 1: pre-infusion, end-of-infusion, and 1 and 3 hours after the end-of S-531011 infusion, and 24, 48, 72 hours after the start of S-531011 infusion (each cycle is 21 days). Part A: Progression-free Survival From first dose up to a maximum of 18 months after last dose; 2.5 years All Parts: Serum concentrations of S-531011 Cycle 1, Day 1: pre-infusion, end-of-infusion, and 1 and 3 hours after the end-of S-531011 infusion, and 24, 48, 72 hours after the start of S-531011 infusion (each cycle is 21 days). Part A: Area Under the Concentration-time Curve Extrapolated from Time Zero to Infinity (AUCinf) of S-531011 Cycle 1, Day 1: pre-infusion, end-of-infusion, and 1 and 3 hours after the end-of S-531011 infusion, and 24, 48, 72 hours after the start of S-531011 infusion (each cycle is 21 days). Part A: Total Clearance (CL) of S-531011 Cycle 1, Day 1: pre-infusion, end-of-infusion, and 1 and 3 hours after the end-of S-531011 infusion, and 24, 48, 72 hours after the start of S-531011 infusion (each cycle is 21 days). Part A: Area Under the Concentration-time Curve from Time Zero to the Time of Last Quantifiable Concentration After Dosing (AUC0-last) of S-531011 Cycle 1, Day 1: pre-infusion, end-of-infusion, and 1 and 3 hours after the end-of S-531011 infusion, and 24, 48, 72 hours after the start of S-531011 infusion (each cycle is 21 days). Part A: Maximum Serum Concentration (Cmax) of S-531011 Cycle 1, Day 1: pre-infusion, end-of-infusion, and 1 and 3 hours after the end-of S-531011 infusion, and 24, 48, 72 hours after the start of S-531011 infusion (each cycle is 21 days). Part A: Time to Maximum Serum Concentration (Tmax) of S-531011 Cycle 1, Day 1: pre-infusion, end-of-infusion, and 1 and 3 hours after the end-of S-531011 infusion, and 24, 48, 72 hours after the start of S-531011 infusion (each cycle is 21 days). Part A: Terminal Elimination Half-life (t1/2,z) of S-531011 Cycle 1, Day 1: pre-infusion, end-of-infusion, and 1 and 3 hours after the end-of S-531011 infusion, and 24, 48, 72 hours after the start of S-531011 infusion (each cycle is 21 days). All Parts: Anti-S-531011 Antibody (ADA) Titer Level Day 1 of Cycles 1 to 9 (each cycle is 21 days) Part B and C: Number of Participants with Treatment-emergent Adverse Events (TEAEs) Approximately 12 months Part A: Objective Response Rate Every 6 weeks for the first 24 weeks and every 9 weeks thereafter, until the end of treatment (approximately 12 months). Part A: Volume of Distribution at Steady State (Vss) of S-531011 Cycle 1, Day 1: pre-infusion, end-of-infusion, and 1 and 3 hours after the end-of S-531011 infusion, and 24, 48, 72 hours after the start of S-531011 infusion (each cycle is 21 days). Part A: Mean Residence Time (MRT) of S-531011 Cycle 1, Day 1: pre-infusion, end-of-infusion, and 1 and 3 hours after the end-of S-531011 infusion, and 24, 48, 72 hours after the start of S-531011 infusion (each cycle is 21 days). All Parts: Changes in serum tumor markers from pretreatment to on-treatment Baseline and Day 1 of each treatment cycle (each cycle is 21 days) Part A: Duration of Response From first dose up to a maximum of 18 months after last dose; 2.5 years
Trial Locations
- Locations (6)
Henry Ford Health Center
🇺🇸Detroit, Michigan, United States
National Cancer Center Hospital East
🇯🇵Kashiwa, Chiba, Japan
Angeles Clinic and Research Center
🇺🇸Los Angeles, California, United States
Fox Chase Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
Osaka University Hospital
🇯🇵Suita, Osaka, Japan
National Cancer Center Hospital
🇯🇵Chuo Ku, Tokyo, Japan