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

NCT05101070 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: 2023P2411KEYNOTE-D85MK-3475-D85
• Study Type: interventional
• Target: 282
• Locations: 2 countries
• Sites: 8

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 with or without pembrolizumab. The primary objective of Parts B and C is to evaluate the antitumor activity of S-531011 at the RP2D with or without pembrolizumab. The primary objective of Parts D and E is to evaluate the antitumor activity of S-531011 at the RP2D in combination with bevacizumab with our without pembrolizumab.

Conditions

Solid Tumors

Keywords

C-C motif chemokine receptor 8 (CCR8)

Outcome Measures

Primary Outcomes (7)

• Part A: Number of Participants with Treatment-emergent Adverse Events (TEAEs)

  Approximately 12 months (Part A-1); Approximately 24 months (Part A-2)

• Parts B, C, D, E: Objective Response Rate

  Every 6 weeks for the first 24 weeks and every 9 weeks thereafter, until disease progression (Approximately 12 months [Part B]; Approximately 24 months [Parts C, D, E])

• Parts B, C, D, E: Duration of Response

  Every 6 weeks for the first 24 weeks and every 9 weeks thereafter, until disease progression (Approximately 12 months [Part B]; Approximately 24 months [Parts C, D, E])

• Parts B, C, D, E: Disease Control Rate

  Every 6 weeks for the first 24 weeks and every 9 weeks thereafter, until disease progression (Approximately 12 months [Part B]; Approximately 24 months [Parts C, D, E])

• Parts B, C, D, E: Time to Response

  Every 6 weeks for the first 24 weeks and every 9 weeks thereafter, until disease progression (Approximately 12 months [Part B]; Approximately 24 months [Parts C, D, E])

• Parts B, C, D, E: Progression-free Survival

  Every 6 weeks for the first 24 weeks and every 9 weeks thereafter, until disease progression (Approximately 12 months [Part B]; Approximately 24 months [Parts C, D, E])

• Parts B, C, D, E: Overall Survival

  Every 6 weeks for the first 24 weeks and every 9 weeks thereafter, until disease progression (Approximately 12 months [Part B]; Approximately 24 months [Parts C, D, E])

Secondary Outcomes (19)

• Part A: Objective Response Rate

  Every 6 weeks for the first 24 weeks and every 9 weeks thereafter, until disease progression (Approximately 12 months [Part A-1]; Approximately 24 months [Part A-2])

• Part A: Duration of Response

  Every 6 weeks for the first 24 weeks and every 9 weeks thereafter, until disease progression (Approximately 12 months [Part A-1]; Approximately 24 months [Part A-2])

• Part A: Disease Control Rate

  Every 6 weeks for the first 24 weeks and every 9 weeks thereafter, until disease progression (Approximately 12 months [Part A-1]; Approximately 24 months [Part A-2])

• Part A: Time to Response

  Every 6 weeks for the first 24 weeks and every 9 weeks thereafter, until disease progression (Approximately 12 months [Part A-1]; Approximately 24 months [Part A-2])

• Part A: Progression-free Survival

  Every 6 weeks for the first 24 weeks and every 9 weeks thereafter, until disease progression (Approximately 12 months [Part A-1]; Approximately 24 months [Part A-2])

Study Arms (6)

Part A-1: S-531011 Monotherapy

EXPERIMENTAL

Participants will receive escalating doses of S-531011 by intravenous infusion for up to approximately 12 months.

Drug: S-531011

Part A-2: S-531011 + Pembrolizumab

EXPERIMENTAL

Participants will receive escalating doses of S-531011 in combination with pembrolizumab by intravenous infusion for up to approximately 24 months.

Drug: S-531011; Drug: Pembrolizumab

Part B: S-531011 Monotherapy

EXPERIMENTAL

Participants will receive S-531011 at the RP2D by intravenous infusion for up to approximately 12 months.

Drug: S-531011

Part C: S-531011 + Pembrolizumab

EXPERIMENTAL

Participants will receive S-531011 at the RP2D in combination with pembrolizumab by intravenous infusion for up to approximately 24 months.

Drug: S-531011; Drug: Pembrolizumab

Part D: S-531011 + Bevacizumab

EXPERIMENTAL

Participants will receive S-531011 at the RP2D in combination with bevacizumab or bevacizumab biosimilar by intravenous infusion for up to approximately 24 months.

Drug: S-531011; Drug: Bevacizumab

Part E: S-531011 + Bevacizumab + Pembrolizumab

EXPERIMENTAL

Participants will receive S-531011 at the RP2D in combination with bevacizumab or bevacizumab biosimilar and pembrolizumab by intravenous infusion for up to approximately 24 months.

Drug: S-531011; Drug: Pembrolizumab; Drug: Bevacizumab

Interventions

Bevacizumab DRUG

Administered by intravenous infusion

Also known as: Avastin

Part D: S-531011 + Bevacizumab; Part E: S-531011 + Bevacizumab + Pembrolizumab

S-531011 DRUG

Administered by intravenous infusion

Part A-1: S-531011 Monotherapy; Part A-2: S-531011 + Pembrolizumab; Part B: S-531011 Monotherapy; Part C: S-531011 + Pembrolizumab; Part D: S-531011 + Bevacizumab; Part E: S-531011 + Bevacizumab + Pembrolizumab

Pembrolizumab DRUG

Administered by intravenous infusion

Also known as: KEYTRUDA

Part A-2: S-531011 + Pembrolizumab; Part C: S-531011 + Pembrolizumab; Part E: S-531011 + Bevacizumab + Pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 Response Evaluation Criteria in Solid Tumors version 1.1.
• (Part A only) Participants should have 1 of the following tumor types: malignant melanoma, head and neck squamous cell carcinoma, renal cell carcinoma, urothelial carcinoma, non-small cell lung cancer, or triple-negative breast cancer, esophageal cancer (esophageal squamous cell carcinoma and adenocarcinoma), or gastric cancer (gastric and gastroesophageal junction adenocarcinoma). Participants with colorectal cancer (CRC), pancreatic cancer, cervical cancer, epithelial ovarian cancer, 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.
• (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 rat sarcoma virus (RAS) (Kirsten RAS/neuroblastoma 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.
• (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.
• (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 drugs approved in the country, or investigational drugs.
• Participants should be willing and able to provide permission to access archival formalin-fixed paraffin-embedded 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.
• (Part A and B/CRC Cohorts only; 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 (flow cytometry) analysis.
• Eastern Cooperative Oncology Group Performance Status 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 ≤ 480 milliseconds in 12- lead electrocardiogram at Screening.

You may not qualify if:

• Presence or history of autoimmune diseases or immune-mediated diseases that require chronic use of systemic corticosteroids (\> 10 milligrams 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 classification III or IV.
• A positive test for hepatitis B surface antigen and/or hepatitis C virus (HCV) antibody (participants with positive HCV antibody are eligible if a confirmatory HCV RNA test is undetectable).
• A positive serological test for human immunodeficiency virus 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 have discontinued breastfeeding) or trying to become pregnant.
• (Parts D and E only) Serious non-healing wound, non-healing ulcer, or non healing bone fracture.
• (Parts D and E only) Presence or history of severe arterial thromboembolic events (for example, 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 (for example, 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.
• (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.
• (Parts D and E only) Presence or history of any life-threatening vascular endothelial growth factor (VEGF)-related adverse event (AE).
• (Parts D and E only) Proteinuria ≥ 2+ by urine dipstick test within 4 weeks prior to the first dose of study intervention.

Sponsors & Collaborators

• Shionogi: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (8)

Angeles Clinic and Research Center

Los Angeles, California, 90025, United States

ACTIVE NOT RECRUITING

University of Florida Health

Gainesville, Florida, 32610, United States

RECRUITING

Henry Ford Health Center

Detroit, Michigan, 48202, United States

ACTIVE NOT RECRUITING

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

RECRUITING

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

National Cancer Center Hospital East

Kashiwa, Chiba, Japan

RECRUITING

The University of Osaka Hospital

Suita, Osaka, Japan

RECRUITING

National Cancer Center Hospital

Chuo Ku, Tokyo, Japan

RECRUITING

MeSH Terms

Interventions

pembrolizumab; Bevacizumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Shionogi Clinical Trials Administrator Clinical Support Help Line

  Shionogi

  STUDY DIRECTOR

Central Study Contacts

Shionogi Clinical Trials Administrator Clinical Support Help Line

CONTACT

800-849-9707; Shionogiclintrials-admin@shionogi.co.jp

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 14, 2021
• First Posted: November 1, 2021
• Study Start: May 30, 2022
• Primary Completion (Estimated): May 31, 2028
• Study Completion (Estimated): May 31, 2028
• Last Updated: March 18, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (5); JP (3)