aCCeleR8-001: S-531011 as Monotherapy and in Combination With an Immune Checkpoint Inhibitor in Advanced or Metastatic Solid Tumors
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1/Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Part A-1: S-531011 Monotherapy Participants will receive escalating doses of S-531011 by intravenous infusion for up to approximately 12 months. |
Drug: S-531011
Administered by intravenous infusion
|
| Experimental: Part A-2: S-531011 + Pembrolizumab Participants will receive escalating doses of S-531011 in combination with pembrolizumab by intravenous infusion for up to approximately 12 months. |
Drug: S-531011
Administered by intravenous infusion
Drug: Pembrolizumab
Administered by intravenous infusion
Other Names:
|
| Experimental: Part B: S-531011 Monotherapy Participants will receive S-531011 at the the RP2D by intravenous infusion for up to approximately 12 months. |
Drug: S-531011
Administered by intravenous infusion
|
| Experimental: Part C: S-531011 + Pembrolizumab Participants will receive S-531011 at the RP2D in combination with pembrolizumab by intravenous infusion for up to approximately 12 months. |
Drug: Pembrolizumab
Administered by intravenous infusion
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Part A: Number of Participants with Treatment-emergent Adverse Events (TEAEs) [Approximately 12 months]
- 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: 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: Time to Response [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]
- Parts B and C: Overall Survival [From first dose up to a maximum of 18 months after last dose; 2.5 years]
Secondary Outcome Measures
- 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: Duration of Response [From first dose up to a maximum of 18 months after last dose; 2.5 years]
- 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: Progression-free Survival [From first dose up to a maximum of 18 months after last dose; 2.5 years]
- Part A: 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).]
- All Parts: 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: 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: 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: 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: 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).]
- Part A: Total Clearance 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: 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: Anti-S-531011 Antibody (ADA) Titer Level [Day 1 of Cycles 1 to 9 (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 B and C: Number of Participants with Treatment-emergent Adverse Events (TEAEs) [Approximately 12 months]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Male or female participant must be at least 18 years of age inclusive (or complies with country-specific regulatory requirements, at least 20 years of age in Japan), 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 completion of Part A-1.
-
(Part C only) Participants should have 1 of specific histologically or cytologically confirmed tumor types selected by the sponsor after completion of 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.
-
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.
-
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 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.
-
Clinical evidence of any active second invasive malignancy (except stable prostate cancer on watchful waiting).
-
(Parts A-2 and C only): Participants who developed an immune-related adverse event (irAE) during prior pembrolizumab treatment that required a delay in the scheduled administration for more than 4 weeks due to any grade of irAEs or led to permanent discontinuation of pembrolizumab. Also, participants whose previous irAE due to pembrolizumab has not resolved to ≤ Grade 1 and/or still requires corticosteroids (> 10 mg of prednisone-equivalent per day).
-
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).
-
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 a live, attenuated vaccine within 28 days before the first dose of study intervention.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | National Cancer Center Hospital East | Kashiwa | Chiba | Japan | |
| 2 | Osaka University Hospital | Suita | Osaka | Japan | |
| 3 | National Cancer Center Hospital | Chuo Ku | Tokyo | Japan |
Sponsors and Collaborators
- Shionogi Inc.
Investigators
- Study Director: Shionogi Clinical Trials Administrator Clinical Support Help Line, Shionogi
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2023P2411