A Multicenter, Phase Ib/II Clinical Trial to Evaluate the Efficacy and Safety of Concurrent Combination Therapy of S-531011 Plus Fruquintinib or S-531011 Plus Fruquintinib Plus Pembrolizumab in Patients With MSS/pMMR Colorectal Cancer

NCT07591597 | Not Yet Recruiting Phase 1 DMC

• 2 other identifiers: EPOC2501jRCT2031260047
• Study Type: interventional
• Target: 68
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study aims to evaluate the efficacy and safety of the concurrent combination therapy of S 531011 + fruquintinib or S 531011 + fruquintinib + pembrolizumab in patients with MSS/pMMR colorectal cancer.

Conditions

Metastatic Colorectal Neoplasms; Microsatellite Stable / Proficient Mismatch Repair Colorectal Cancer

Keywords

Colorectal Neoplasms; Metastatic Colorectal Cancer; Microsatellite Stability; DNA Mismatch Repair; Receptors, CCR8; CCR8 Antagonists; Fruquintinib; Pembrolizumab; Antibodies, Monoclonal; Immune Checkpoint Inhibitors; VEGFR Inhibitors; Combination Drug Therapy; Phase Ib Clinical Trial; Phase II Clinical Trial

Outcome Measures

Primary Outcomes (2)

• Dose-Limiting Toxicity (DLT) Rate [Phase Ib Part]

  Percentage of participants experiencing dose-limiting toxicities (DLTs).

  Up to 29 days after first dose

• Objective Response Rate (ORR) [Phase II Part]

  Objective response rate assessed by the principal investigator or sub-investigator.Participants treated at the recommended dose in Phase Ib are included.

  From baseline to objective disease progression or death, assessed up to 24 months.

Secondary Outcomes (13)

• Maximum Observed Serum Concentration of S-531011 (Cmax)

  From the first through the ninth administration of S-531011 (each cycle is 21 days) and at 30 days after the final administration

• Time to Maximum Observed Serum Concentration of S-531011 (Tmax)

  From the first through the ninth administration of S-531011 (each cycle is 21 days) and at 30 days after the final administration

• Area Under the Serum Concentration-Time Curve of S-531011 (AUC)

  From the first through the ninth administration of S-531011 (each cycle is 21 days) and at 30 days after the final administration

• Terminal Elimination Half-Life of S-531011 (t1/2)

  From the first through the ninth administration of S-531011 (each cycle is 21 days) and at 30 days after the final administration

• Anti-S-531011 Antibody (ADA) Titer

  From the first through the ninth administration of S-531011 (each cycle is 21 days) and at 30 days after the final administration

Study Arms (2)

Arm A S-531011 + Fruquintinib

EXPERIMENTAL

Participants receive S-531011 and fruquintinib. In the Phase Ib part, dose levels may vary according to the dose finding scheme. In Phase II, the recommended dose determined in Phase Ib will be used.

Biological: S-531011; Drug: Fruquintinib

Arm B S-531011 + Fruquintinib + Pembrolizumab

EXPERIMENTAL

Participants receive S-531011, fruquintinib, and pembrolizumab. In the Phase Ib part, dose levels of S-531011 and fruquintinib may vary according to the dose finding scheme. In Phase II, the recommended dose determined in Phase Ib will be used. Pembrolizumab is administered at a fixed dose throughout both the Phase Ib and Phase II parts.

Biological: S-531011; Drug: Fruquintinib; Biological: Pembrolizumab

Interventions

S-531011 BIOLOGICAL

S-531011 will be administered intravenously once every 3 weeks (q3w). In the Phase Ib part, A reduced dose of S-531011 may be used in Dose Level -1 according to the predefined dose-finding scheme by evaluating DLT profile. In the Phase II part, S-531011 will be administered at the recommended dose determined in the Phase Ib part.

Arm A S-531011 + Fruquintinib; Arm B S-531011 + Fruquintinib + Pembrolizumab

Fruquintinib DRUG

Fruquintinib will be administered orally once daily on Days 1-21 of each 28-day cycle. In the Phase Ib part, fruquintinib will be started at 5 mg (Dose Level 0). A reduced dose of 4 mg may be used in Dose Level -1 according to the predefined dose-finding scheme by evaluating DLT profile. In the Phase II part, fruquintinib will be administered at the recommended dose determined in the Phase Ib part.

Also known as: FRUZAQLA

Arm A S-531011 + Fruquintinib; Arm B S-531011 + Fruquintinib + Pembrolizumab

Pembrolizumab BIOLOGICAL

Pembrolizumab will be administered intravenously at a dose of 200 mg once every 3 weeks (q3w).

Also known as: KEYTRUDA

Arm B S-531011 + Fruquintinib + Pembrolizumab

Eligibility Criteria

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

You may qualify if:

• Patients with histologically confirmed unresectable adenocarcinoma of the colon or rectum.
• Confirmed microsatellite stable (MSS) or proficient mismatch repair (pMMR) status.
• Prior treatment with standard systemic chemotherapy and refractory or intolerant\* to such therapies. Standard chemotherapy must include all of the following:
• \- Fluoropyrimidine, irinotecan, and oxaliplatin (with or without anti-VEGF antibody therapy)
• \- For patients with RAS and BRAF wild-type tumors: prior treatment with anti-EGFR monoclonal antibody (cetuximab or panitumumab)
• \- For patients with BRAF V600E mutation: prior treatment with a BRAF inhibitor (encorafenib)
• \*For patients who relapse during adjuvant chemotherapy or within 6 months after the last dose of postoperative adjuvant chemotherapy, that adjuvant therapy counts as prior systemic therapy.
• Presence of measurable disease according to RECIST version 1.1.
• Age ≥ 18 years at the time of informed consent.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Laboratory values within 14 days prior to enrollment meeting all of the following (tests performed on the same weekday 2 weeks before the enrollment date are acceptable):
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• Absolute neutrophil count ≥ 1,500/mm³
• Hemoglobin ≥ 9.0 g/dL
• Platelet count ≥ 75,000/mm³

You may not qualify if:

• Prior treatment with fruquintinib for metastatic colorectal cancer.
• Prior treatment with any anti-CCR8 antibody, regardless of indication.
• Receipt of chemotherapy, radiotherapy, immunotherapy, or any antitumor therapy, or investigational agents within 14 days prior to enrollment, or persistence of CTCAE Grade ≥ 2 toxicities from prior therapies (excluding alopecia, hyperpigmentation, and peripheral sensory neuropathy).
• History of acute coronary syndrome (including myocardial infarction or unstable angina), coronary angioplasty, or stent placement within 6 months prior to enrollment.
• History or current findings of congestive heart failure of NYHA Class III or higher.
• Uncontrolled hypertension.
• Known central nervous system metastases. (If CNS metastasis is clinically suspected, brain CT or MRI must be performed during screening.)
• Active double primary malignancy (simultaneous or metachronous with disease-free interval \< 2 years), except for carcinoma in situ or intramucosal carcinoma lesions considered curable by local therapy.
• Serious comorbidities requiring inpatient treatment (e.g., paralytic ileus, bowel obstruction, pulmonary fibrosis, uncontrolled diabetes, heart failure, myocardial infarction, angina, renal failure, hepatic failure, psychiatric disorders, cerebrovascular disorders, or transfusion-requiring ulcers).
• Active infections, including:
• \- HBs antigen positive
• Patients may be eligible if receiving nucleoside analog antiviral therapy and HBV-DNA \< 20 IU/mL (1.3 log IU/mL).
• \- HBs antibody positive or HBc antibody positive AND HBV-DNA positive
• If HBV-DNA \< 20 IU/mL, the patient may be eligible. - HCV antibody positive
• Patients may be eligible if HCV-RNA is below the detection limit. - HIV positive

Sponsors & Collaborators

• National Cancer Center Hospital East: lead
• Shionogi: collaborator

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

HMPL-013; pembrolizumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Central Study Contacts

Akihito Kawazoe, MD

CONTACT

+81-4-7133-1111; ignite-crc_core@east.ncc.go.jp

Kazumasa Yamamoto, MD

CONTACT

+81-4-7133-1111; ignite-crc_core@east.ncc.go.jp

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief, Department of Gastrointestinal Oncology

Model Details: This study uses a parallel assignment model with two experimental arms (Arm A and Arm B). Enrollment into Arm B will begin only after enrollment into Arm A has been completed. Participants will receive the assigned intervention throughout the study without crossover between arms.

Study Record Dates

• First Submitted: April 13, 2026
• First Posted: May 18, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): May 1, 2029
• Last Updated: May 18, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share