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S-531011 as Monotherapy and in Combination With an Immune Checkpoint Inhibitor in Advanced or Metastatic Solid Tumors (aCCeleR8-001)

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ClinicalTrials.gov Identifier: NCT05101070
Recruitment Status : Recruiting
First Posted : November 1, 2021
Last Update Posted : March 25, 2024
Sponsor:
Collaborator:
Merck Sharp & Dohme LLC
Information provided by (Responsible Party):
Shionogi Inc. ( 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.


Condition or disease Intervention/treatment Phase
Solid Tumors Drug: S-531011 Drug: pembrolizumab Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 274 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : May 30, 2022
Estimated Primary Completion Date : April 16, 2027
Estimated Study Completion Date : April 16, 2027

Resource links provided by the National Library of Medicine


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 Name: KEYTRUDA®

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: S-531011
Administered by intravenous infusion

Drug: pembrolizumab
Administered by intravenous infusion
Other Name: KEYTRUDA®




Primary Outcome Measures :
  1. Part A: Number of Participants with Treatment-emergent Adverse Events (TEAEs) [ Time Frame: Approximately 12 months ]
  2. Parts B and C: Objective Response Rate [ Time Frame: Every 6 weeks for the first 24 weeks and every 9 weeks thereafter, until the end of treatment (approximately 12 months). ]
  3. Parts B and C: Duration of Response [ Time Frame: From first dose up to a maximum of 18 months after last dose; 2.5 years ]
  4. Parts B and C: Disease Control Rate [ Time Frame: Every 6 weeks for the first 24 weeks and every 9 weeks thereafter, until the end of treatment (approximately 12 months). ]
  5. Parts B and C: Time to Response [ Time Frame: Every 6 weeks for the first 24 weeks and every 9 weeks thereafter, until the end of treatment (approximately 12 months). ]
  6. Parts B and C: Progression-free Survival [ Time Frame: From first dose up to a maximum of 18 months after last dose; 2.5 years ]
  7. Parts B and C: Overall Survival [ Time Frame: From first dose up to a maximum of 18 months after last dose; 2.5 years ]

Secondary Outcome Measures :
  1. Part A: Objective Response Rate [ Time Frame: Every 6 weeks for the first 24 weeks and every 9 weeks thereafter, until the end of treatment (approximately 12 months). ]
  2. Part A: Duration of Response [ Time Frame: From first dose up to a maximum of 18 months after last dose; 2.5 years ]
  3. Part A: Disease Control Rate [ Time Frame: Every 6 weeks for the first 24 weeks and every 9 weeks thereafter, until the end of treatment (approximately 12 months). ]
  4. Part A: Time to Response [ Time Frame: Every 6 weeks for the first 24 weeks and every 9 weeks thereafter, until the end of treatment (approximately 12 months). ]
  5. Part A: Progression-free Survival [ Time Frame: From first dose up to a maximum of 18 months after last dose; 2.5 years ]
  6. All Parts: Serum concentrations of S-531011 [ Time Frame: 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). ]
  7. Part A: Maximum Serum Concentration (Cmax) of S-531011 [ Time Frame: 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). ]
  8. Part A: Time to Maximum Serum Concentration (Tmax) of S-531011 [ Time Frame: 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). ]
  9. 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 [ Time Frame: 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). ]
  10. Part A: Area Under the Concentration-time Curve Extrapolated from Time Zero to Infinity (AUCinf) of S-531011 [ Time Frame: 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). ]
  11. Part A: Terminal elimination rate constant (λz) of S-531011 [ Time Frame: 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). ]
  12. Part A: Terminal Elimination Half-life (t1/2,z) of S-531011 [ Time Frame: 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). ]
  13. Part A: Total Clearance (CL) of S-531011 [ Time Frame: 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). ]
  14. Part A: Volume of Distribution at Steady State (Vss) of S-531011 [ Time Frame: 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). ]
  15. Part A: Mean Residence Time (MRT) of S-531011 [ Time Frame: 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). ]
  16. All Parts: Anti-S-531011 Antibody (ADA) Titer Level [ Time Frame: Day 1 of Cycles 1 to 9 (each cycle is 21 days) ]
  17. All Parts: Changes in serum tumor markers from pretreatment to on-treatment [ Time Frame: Baseline and Day 1 of each treatment cycle (each cycle is 21 days) ]
  18. Part B and C: Number of Participants with Treatment-emergent Adverse Events (TEAEs) [ Time Frame: Approximately 12 months ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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), 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05101070


Contacts
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Contact: Shionogi Clinical Trials Administrator Clinical Support Help Line 800-849-9707 Shionogiclintrials-admin@shionogi.co.jp

Locations
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United States, California
Angeles Clinic and Research Center Recruiting
Los Angeles, California, United States, 90025
United States, Michigan
Henry Ford Health Center Recruiting
Detroit, Michigan, United States, 48202
United States, Pennsylvania
Fox Chase Cancer Center Recruiting
Philadelphia, Pennsylvania, United States, 19111
Japan
National Cancer Center Hospital East Recruiting
Kashiwa, Chiba, Japan
Osaka University Hospital Recruiting
Suita, Osaka, Japan
National Cancer Center Hospital Recruiting
Chuo Ku, Tokyo, Japan
Sponsors and Collaborators
Shionogi
Merck Sharp & Dohme LLC
Investigators
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Study Director: Shionogi Clinical Trials Administrator Clinical Support Help Line Shionogi
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Responsible Party: Shionogi
ClinicalTrials.gov Identifier: NCT05101070    
Other Study ID Numbers: 2023P2411
KEYNOTE-D85 ( Other Identifier: Merck )
MK-3475-D85 ( Other Identifier: Merck )
First Posted: November 1, 2021    Key Record Dates
Last Update Posted: March 25, 2024
Last Verified: March 2024

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Shionogi Inc. ( Shionogi ):
C-C motif chemokine receptor 8 (CCR8)
Additional relevant MeSH terms:
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Neoplasms
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action