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
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
Kawazoe Akihito
National Cancer Center Hospital East
6-5-1 Kashiwanoha, Kashiwa-shi Chiba, 277-8577 Japan
+81-4-7133-1111
ignite-crc_core@east.ncc.go.jp
Secretariat of clinical trial coordinating committ
National Cancer Center Hospital East
6-5-1 Kashiwanoha, Kashiwa-shi Chiba, 277-8577 Japan
+81-4-7133-1111
ignite-crc_core@east.ncc.go.jp
Recruiting
May. 01, 2026
68
Interventional
non-randomized controlled trial
open(masking not used)
uncontrolled control
single assignment
treatment purpose
1. Patients with histologically confirmed unresectable adenocarcinoma of the colon or rectum.
2. Confirmed microsatellite stable (MSS) or proficient mismatch repair (pMMR) status.
3. 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.
4. Presence of measurable disease according to RECIST version 1.1.
5. Age >= 18 years at the time of informed consent.
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
7. 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):
(1) Absolute neutrophil count >= 1,500/mm3
(2) Hemoglobin >= 9.0 g/dL
(3) Platelet count >= 75,000mm3
(4) Total bilirubin =< 1.5 x institutional upper limit of normal (ULN)
(5) AST (GOT) =< 2.5 x ULN; =< 5 x ULN if liver metastases are present
(6) ALT (GPT) =< 2.5 x ULN; =< 5 x ULN if liver metastases are present
(7) Creatinine =< 1.5 mg/dL
(8) Proteinuria =< 1+ or < 1.0 g/24 h (urine protein-to-creatinine ratio < 1 may be used; if 24-hour urine is collected, the measured value takes precedence)
8. No blood transfusion within 7 days prior to enrollment (a transfusion given on the same weekday 1 week earlier is considered ineligible).
9. Women of childbearing potential must have a negative pregnancy test within 14 days prior to enrollment. Both male and female participants must agree to use appropriate contraception during the study and for 4 months after the last dose of study treatment. Female participants must also agree not to breastfeed during the study and for 4 months after the last dose. (Tests performed on the same weekday 2 weeks before the enrollment date are acceptable.)
10. Able to take oral medication.
11. Written informed consent obtained from the participant.
1. Prior treatment with fruquintinib for metastatic colorectal cancer.
2. Prior treatment with any anti-CCR8 antibody, regardless of indication.
3. 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).
4. History of acute coronary syndrome (including myocardial infarction or unstable angina), coronary angioplasty, or stent placement within 6 months prior to enrollment.
5. History or current findings of congestive heart failure of NYHA Class III or higher.
6. Uncontrolled hypertension.
7. Known central nervous system metastases. (If CNS metastasis is clinically suspected, brain CT or MRI must be performed during screening.)
8. 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.
9. 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).
10. 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
Patients may be eligible if HIV infection is ruled out by confirmatory testing.
- Other active infections requiring treatment.
11. History of autoimmune disease or chronic/recurrent autoimmune disease (patients with type 1 diabetes, hypothyroidism manageable with hormone replacement, or localized skin diseases such as vitiligo, psoriasis, or alopecia not requiring systemic therapy are eligible).
12. Requirement for systemic corticosteroids or immunosuppressive agents, or receipt of such therapy within 2 weeks prior to enrollment (treatment given on the same weekday 2 weeks earlier renders the patient ineligible), except for temporary administration for testing, allergic reactions, or edema associated with radiotherapy.
13. Lack of willingness or inability to comply with study procedures.
14. Considered unsuitable for the study by the principal investigator or sub-investigator.
18age old over
No limit
Both
Metastatic Colorectal Neoplasms,Microsatellite Stable / Proficient Mismatch Repair Colorectal Cancer
This study will be conducted in the following two arms:
Arm A: S-531011 administered in combination with fruquintinib
Arm B: S-531011 administered in combination with fruquintinib and pembrolizumab
The administration of each investigational product is as follows:
-S-531011: Administered by intravenous infusion, with a 3-week cycle.
-Fruquintinib: Administered in 4-week cycles at a dose of 5 mg or 4 mg, orally once daily for 21 consecutive days, followed by a planned 7-day rest period.
-Pembrolizumab: Administered by intravenous infusion at a fixed dose of 200 mg, with a 3-week cycle.
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.
1. Dose-Limiting Toxicity (DLT) Rate [Phase Ib Part]
Percentage of participants experiencing dose-limiting toxicities (DLTs).
2. 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.
3. Pharmacokinetics [Phase Ib Part]
Evaluation of pharmacokinetic parameters of study drugs.
4. Duration of Response (DoR) [Phase Ib/II Part]
Duration of confirmed objective response.
5. Disease Control Rate (DCR) [Phase Ib/II Part]
Percentage of participants achieving CR, PR, or SD.
6. Progression-Free Survival (PFS) [Phase Ib/II Part]
Time from enrollment to radiological progression or death.
7. Overall Survival (OS) [Phase Ib/II Part]
Time from enrollment to death.
8. Incidence of Adverse Events [Phase Ib/II Part]
Percentage of participants experiencing adverse events.
