Suvemcitug plus trifluridine/tipiracil for refractory metastatic colorectal cancer

A Phase Ib/III Study of Suvemcitug Plus Trifluridine/Tipiracil Tablets (FTD/TPI) Versus Placebo Plus Trifluridine/Tipiracil Tablets in Participants With Refractory Metastatic Colorectal Cancer

This trial will test whether adding suvemcitug to trifluridine/tipiracil helps people with refractory metastatic colorectal cancer who have already had standard chemotherapy.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 464 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Jiangsu Simcere Pharmaceutical Co., Ltd. (industry)
• Drugs / interventions: chemotherapy, prednisone
• Locations: 6 sites (Fuzhou, Fujian and 5 other locations)
• Trial ID: NCT07361003 on ClinicalTrials.gov

What this trial studies

The study includes a Phase Ib safety cohort of about 30 participants and a randomized Phase III portion of about 434 participants (total ~464) with unresectable metastatic colorectal adenocarcinoma. In Phase III, participants are randomized 1:1 to receive suvemcitug plus trifluridine/tipiracil or placebo plus trifluridine/tipiracil, with treatment continued until prespecified discontinuation criteria. Investigators will track tumor responses, adverse events, and quality of life during treatment and will follow participants for subsequent therapies and survival after stopping study drug. Eligible patients must have progressed after fluorouracil-, oxaliplatin-, and irinotecan-based chemotherapy and have known RAS status and prior or unsuitable status for anti‑VEGF (and anti‑EGFR if RAS wild-type) therapy.

Who should consider this trial

Good fit: Ideal candidates are adults with unresectable metastatic colorectal adenocarcinoma whose disease progressed after fluorouracil, oxaliplatin, and irinotecan, who have adequate organ and bone marrow function and known RAS status, and who have had or are unsuitable for anti‑VEGF/anti‑EGFR therapy.

Not a fit: Patients with symptomatic central nervous system metastases, a recent second primary malignancy, poor organ or marrow function, or those unable to tolerate trifluridine/tipiracil or intravenous antibody therapy are unlikely to benefit.

Why it matters

Potential benefit: If successful, this combination could offer an additional treatment option that improves tumor control or survival for patients with refractory metastatic colorectal cancer.

How similar studies have performed: Combinations of trifluridine/tipiracil with anti‑VEGF agents such as bevacizumab have shown benefit in this setting, so this approach builds on established precedent though suvemcitug itself is less well characterized.

Eligibility criteria

Inclusion Criteria:

* 1\. Confirmed by histological and/or cytological examination as unresectable metastatic colon or rectal adenocarcinoma;
* 2\. At least one measurable tumor lesion (RECIST v1.1);
* 3\. Previously received fluorouracil, oxaliplatin, and irinotecan based chemotherapy; had previously undergone or was unsuitable for anti-VEGF therapy. (For participants with RAS wild-type, had previously undergone or was unsuitable for anti-EGFR therapy.);
* 4\. Refractory metastatic colorectal cancer having progressed on or are intolerant to the last systemic treatment;
* 5\. Good organ and bone marrow function (no administration of hematopoietic growth factors, blood transfusion, or platelets within 14 days before screening hematology test);
* 6\. RAS mutation status confirmed by testing tumor tissue and /or blood sample.

Exclusion Criteria:

* 1\. Having a second active primary malignancy within the past 5 years;
* 2\. Symptomatic central nervous system (CNS) metastases or CNS metastases requiring local CNS-directed therapy (e.g., radiotherapy or surgery) or corticosteroid treatment within 2 weeks prior to the first administration of the study treatment;
* 3\. Any active infection requiring systemic treatment within 2 weeks prior to the initiation of the study treatment;
* 4\. Pleural effusion, pericardial effusion, or ascites that is uncontrolled or has required drainage or medical intervention within 4 weeks prior to the first administration of the study treatment;
* 5\. Received systemic immuno suppressive therapy within 4 weeks prior to randomization (excluding prophylactic use or chronic low-dose steroids \[≤20 mg/day prednisone equivalent dose\]);
* 6\. Currently taking or has recently taken (within 10 days prior to the first dose) aspirin (\>325 mg/day);
* 7\. Active or chronic hepatitis B (HBsAg or HBcAb positive and HBV DNA≥2000 IU/mL or ≥10000 copies/mL) or hepatitis C infection (HCV antibody positive and HCV RNA≥ULN);
* 8\. Clinically significant cardiovascular disease within 6 months prior to the first administration of the study treatment;symptomatic coronary artery disease requiring medication; arrhythmia requiring medication (excluding asymptomatic atrial fibrillation with controlled ventricular rate); QTcF interval \>470 ms at rest state; or uncontrolled hypertension or pulmonary hypertension;
* 9\. Known hereditary or acquired bleeding and thrombotic tendencies (e.g., hemophilia, coagulation disorders, thrombocytopenia, hypersplenism, etc.); clinically significant bleeding events, arterial or deep venous thrombotic events, or superficial venous thrombosis and intermuscular venous thrombosis requiring intervention within 6 months prior to enrollment;
* 10\. Participants with proteinuria (urine protein \>2+ found during screening examinations; or urine protein 2+ with 24-hour urine protein quantification ≥1g/24h);
* 11\. Participants with a history of intestinal obstruction (including incomplete intestinal obstruction) within 1 month prior to enrollment; participants with a history of abdominal fistula, gastrointestinal perforation, or abdominal abscess.

Where this trial is running

Fuzhou, Fujian and 5 other locations

• Fujian Cancer Hospital — Fuzhou, Fujian, China (RECRUITING)
• Harbin Medical University University Cancer Hospital — Harbin, Heilongjiang, China (RECRUITING)
• The First Affiliated Hospital of Nanjing Medical University — Nanjing, Jiangsu, China (RECRUITING)
• Cancer Hospital of Shandong First Medical University — Jinan, Shandong, China (RECRUITING)
• Tianjin Medical University Cancer Institute and Hospital — Tianjin, Tianjin Municipality, China (RECRUITING)
• The Second Affiliated Hospital Zhejiang University School of Medicine — Hangzhou, Zhejiang, China (RECRUITING)

Study contacts

• Study coordinator: Xueyan Li

Conditions: Refractory Metastatic Colorectal Cancer, refractory metastatic colorectal cancer, Suvemcitug, trifluridine/tipiracil