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

Solid Tumors Clinical Trial

— aCCeleR8-001  

Official title:

A Phase 1b/2, Multicenter, Open-label Study of S-531011 as Monotherapy and in Combination With an Immune Checkpoint Inhibitor in Participants With Locally Advanced or Metastatic Solid Tumors

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05101070
• Other study ID #: 2023P2411
• Secondary ID: KEYNOTE-D85MK-34
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: May 30, 2022
• Est. completion date: April 16, 2027

Study information

• Verified date: March 2024
• Source: Shionogi Inc.
• Contact: Shionogi Clinical Trials Administrator Clinical Support Help Lin
• Phone: 800-849-9707
• Email: Shionogiclintrials-admin[@]shionogi.co.jp
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 274
• Est. completion date: April 16, 2027
• Est. primary completion date: April 16, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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), 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.

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 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.

Related Conditions & MeSH terms

• Neoplasms
• Solid Tumors

Intervention

Drug:
• S-531011
Administered by intravenous infusion
• pembrolizumab
Administered by intravenous infusion

Locations

Country	Name	City	State
Japan	National Cancer Center Hospital	Chuo Ku	Tokyo
Japan	National Cancer Center Hospital East	Kashiwa	Chiba
Japan	Osaka University Hospital	Suita	Osaka
United States	Henry Ford Health Center	Detroit	Michigan
United States	Angeles Clinic and Research Center	Los Angeles	California
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Shionogi	Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part A: Number of Participants with Treatment-emergent Adverse Events (TEAEs)		Approximately 12 months
Primary	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).
Primary	Parts B and C: Duration of Response		From first dose up to a maximum of 18 months after last dose; 2.5 years
Primary	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).
Primary	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).
Primary	Parts B and C: Progression-free Survival		From first dose up to a maximum of 18 months after last dose; 2.5 years
Primary	Parts B and C: Overall Survival		From first dose up to a maximum of 18 months after last dose; 2.5 years
Secondary	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).
Secondary	Part A: Duration of Response		From first dose up to a maximum of 18 months after last dose; 2.5 years
Secondary	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).
Secondary	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).
Secondary	Part A: Progression-free Survival		From first dose up to a maximum of 18 months after last dose; 2.5 years
Secondary	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).
Secondary	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).
Secondary	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).
Secondary	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).
Secondary	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).
Secondary	Part A: Terminal elimination rate constant (?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).
Secondary	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).
Secondary	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).
Secondary	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).
Secondary	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).
Secondary	All Parts: Anti-S-531011 Antibody (ADA) Titer Level		Day 1 of Cycles 1 to 9 (each cycle is 21 days)
Secondary	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)
Secondary	Part B and C: Number of Participants with Treatment-emergent Adverse Events (TEAEs)		Approximately 12 months