A Clinical Study of Iparomlimab and Tuvonralimab Combined With Fruquintinib and Heterogeneous Radiotherapy Versus Fruquintinib as Third-Line and Subsequent-Line Treatment for Metastatic Colorectal Cancer

Starting soon · Phase 2

Conditions studied: Metastatic Colorectal Cancer (CRC), mCRC

In brief

This is a randomized, parallel, open-label, multicenter exploratory clinical study designed to investigate the efficacy and safety of iparomlimab and tuvonralimab in combination with fruquintinib plus heterogeneous radiotherapy, compared with fruquintinib monotherapy, as the third-line and subsequent-line treatment for patients with oligometastatic colorectal cancer.

Key facts

Study ID

NCT07502014

Run by

Huazhong University of Science and Technology

People needed

60

Starts

2026-05-01

Expected to finish

2029-12-31

Last updated by the study team

2026-03-30

Who can join

Age: 18 and older, up to 75. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Patients aged 18 to 75 years (inclusive).
• Histologically or cytologically confirmed stage Ⅳ primary colorectal cancer.
• No more than 5 oligometastatic lesions, with metastases usually limited to one or a few specific organs (e.g., liver, lung, etc.), and the metastatic lesions are deemed suitable for stereotactic body radiation therapy (SBRT) by the investigator.
• Failure of at least 2 prior lines of standard therapy (based on fluorouracil, oxaliplatin, irinotecan, bevacizumab, cetuximab).
• Note: Adjuvant/neoadjuvant therapy is permitted. If recurrence occurs during adjuvant/neoadjuvant therapy or within 6 months after its completion, the adjuvant/neoadjuvant therapy will be regarded as the first-line therapy for advanced disease.
• At least one extracranial measurable lesion meeting the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).
• Prior radiotherapy is permitted, but it must be more than 4 weeks before study enrollment. In addition, the lesions selected for radiotherapy and evaluable lesions in this study must be untreated with radiotherapy, and the prior radiotherapy must not affect the normal tissue dose of radiotherapy in this study. (Note: If radiotherapy was received before enrollment, detailed radiotherapy-related parameter data must be provided.)
• If a subject has undergone surgery, he/she must have fully recovered from the toxicities and complications of the surgical intervention before the start of treatment, and enrollment will be considered only after the wound is completely healed.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1.
• Expected survival of ≥12 weeks.
• Adequate function of major organs (no use of any blood components or cell growth factors within 2 weeks before enrollment), meeting the following requirements:
• Bone marrow function: Absolute neutrophil count (ANC) ≥1.5×10⁹/L, white blood cell (WBC) count ≥4.0×10⁹/L, platelet count ≥100×10⁹/L, hemoglobin (Hb) ≥90 g/L.
• Hepatic function: Serum total bilirubin (TBIL) ≤1.5×upper limit of normal (ULN). If serum total bilirubin level >1.5×ULN, direct bilirubin level must be ≤ULN; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×ULN (up to 5×ULN for patients with liver metastases).
• Renal function: Blood urea nitrogen (BUN) and serum creatinine (Cr) ≤1.5×ULN (with creatinine clearance rate (CCr) ≥50 mL/min).
• Cardiac function: Normal cardiac function with left ventricular ejection fraction (LVEF) ≥50%.
• Coagulation function: International normalized ratio (INR) ≤1.5×ULN, activated partial thromboplastin time (APTT) ≤1.5×ULN.
• Male or female patients of childbearing potential must voluntarily use effective contraceptive methods during the study and within 6 months after the last study drug administration, such as double barrier contraception, condoms, oral or injectable contraceptives, intrauterine devices, etc. All female patients will be considered of childbearing potential unless they have natural menopause, artificial menopause, or sterilization (e.g., hysterectomy, bilateral adnexectomy, ovarian irradiation, etc.).

You may not qualify if…

• Prior treatment with anti-PD-1/PD-L1, anti-CTLA-4 agents, or other investigational immunotherapeutic agents.
• Severe autoimmune diseases, including active inflammatory bowel disease (Crohn's disease, ulcerative colitis), rheumatoid arthritis, scleroderma, systemic lupus erythematosus, autoimmune vasculitis (e.g., Wegener's granulomatosis), etc.
• Symptomatic interstitial lung disease or active infectious/non-infectious pneumonitis.
• Risk factors for intestinal perforation: active diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction, abdominal cancer, or other known risk factors for intestinal perforation.
• History of other malignancies; however, patients with cured localized tumors such as basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, carcinoma in situ of the prostate, cervix, or breast may be enrolled.
• Patients planning to undergo or having previously received organ or allogeneic bone marrow transplantation.
• Clinically significant moderate to severe ascites requiring therapeutic paracentesis or drainage, or Child-Pugh score >2 (except for radiologically detected minimal ascites without clinical symptoms); uncontrolled moderate or large pleural effusion or pericardial effusion.
• History of gastrointestinal bleeding or definite bleeding tendency within 6 months prior to initiation of study treatment, including: high-risk or severe esophagogastric varices, active local peptic ulcer lesions, persistent positive fecal occult blood test. (Patients with positive baseline fecal occult blood may be retested; if still positive, esophagogastroduodenoscopy (EGD) is required. Patients with EGD evidence of bleeding-risk varices are excluded.)
• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to initiation of study treatment.
• Known congenital or acquired bleeding disorders (e.g., coagulopathy) or thrombotic tendency such as hemophilia; currently using or having recently used (within 10 days before study treatment) full-dose oral or injectable anticoagulants or thrombolytic agents for therapeutic purposes. (Prophylactic use of low-dose aspirin or low-molecular-weight heparin is permitted.)
• Currently using or having recently used (within 10 days before study treatment) aspirin (> 325 mg/day, maximal antiplatelet dose), dipyridamole, ticlopidine, clopidogrel (≥75 mg), or cilostazol.
• Thrombotic or embolic events within 6 months prior to initiation of study treatment, such as cerebrovascular accident (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), pulmonary embolism, etc.
• Active infection, heart failure, myocardial infarction within 6 months, unstable angina, or uncontrolled arrhythmia.
• Any physical or clinical laboratory abnormality that, in the investigator's opinion, may interfere with study outcomes or increase the risk of treatment complications, or other uncontrolled medical conditions.
• Patients requiring urgent palliative radiotherapy or emergency surgery (spinal cord compression, cerebral herniation, pathological fracture) as judged by the investigator.
• Breastfeeding or pregnant female patients.
• Congenital or acquired immunodeficiency disorders including human immunodeficiency virus (HIV) infection, or history of organ transplantation or allogeneic stem cell transplantation.
• Patients with psychiatric disorders, substance abuse, or social issues affecting compliance, as determined by the treating physician.
• Active infection including active tuberculosis is excluded. Patients with hepatitis B virus (HBV) or hepatitis C virus (HCV) infection may be enrolled if disease is stable following antiviral therapy.
• Administration of live attenuated vaccines within 30 days prior to enrollment. (Note: Injectable seasonal influenza vaccines are mostly inactivated and permitted; intranasal formulations are usually live attenuated and prohibited.)
• Poorly controlled cardiac symptoms or diseases including:
• New York Heart Association (NYHA) Class ≥II cardiac insufficiency or LVEF <50% on echocardiography;
• Unstable angina;
• Myocardial infarction within 1 year prior to initiation of study treatment;
• Clinically significant supraventricular or ventricular arrhythmia requiring treatment or intervention;

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.