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

NCT07502014 | Not Yet Recruiting Phase 2

• 1 other identifier: TJ-IRB202512151
• Study Type: interventional
• Target: 60
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Metastatic Colorectal Cancer (CRC); mCRC

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival

  Defined as the time from the date of a subject's enrollment to the first occurrence of disease progression or death, whichever comes first.

  From date of subject's enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months

Secondary Outcomes (3)

• Objective Response Rate (ORR)

  1 year

• Overall Survival (OS)

  From date of subject's enrollment until the date of death from any cause, assessed up to 100 months

• Disease Control Rate (DCR)

  1 year

Study Arms (2)

Iparomlimab and Tuvonralimab plus Fruquintinib plus Heterogeneous Radiotherapy

EXPERIMENTAL

Fruquintinib 5 mg, oral administration, once daily, 2 weeks on and 1 week off; one cycle every 3 weeks. Continuous administration until disease progression, unacceptable toxicity, voluntary withdrawal of informed consent, or other applicable circumstances in the subjects. Iparomlimab and Tuvonralimab 5 mg/kg, intravenous injection, administered on Day 1 of each cycle; one cycle every 3 weeks. Continuous administration until disease progression, unacceptable toxicity, voluntary withdrawal of informed consent, or other applicable circumstances in the subjects. Heterogeneous Radiotherapy High-dose radiotherapy (SBRT): 8-10 Gy per fraction, 5 fractions in total, once every other day (qod), completed within 10 days. Low-dose radiotherapy (for other lesions): 2 Gy per fraction, a single fraction for each lesion.

Drug: Iparomlimab and Tuvonralimab (QL1706); Drug: Fruquintinib; Radiation: Heterogeneous Radiotherapy

Fruquintinib Administration details: 5 mg, oral administration, once daily, with a schedule of 2 wee

ACTIVE COMPARATOR

Fruquintinib Administration details: 5 mg, oral administration, once daily, with a schedule of 2 weeks on and 1 week off (one cycle every 3 weeks). Continuous administration will be given until the subject experiences disease progression, unacceptable toxicity, voluntary withdrawal of informed consent, or other such circumstances.

Drug: Fruquintinib

Interventions

Iparomlimab and Tuvonralimab (QL1706) DRUG

Dual immune checkpoint inhibitor antibody targeting PD-1 and CTLA-4

Also known as: QL1706

Iparomlimab and Tuvonralimab plus Fruquintinib plus Heterogeneous Radiotherapy

Fruquintinib DRUG

TKI

Fruquintinib Administration details: 5 mg, oral administration, once daily, with a schedule of 2 wee; Iparomlimab and Tuvonralimab plus Fruquintinib plus Heterogeneous Radiotherapy

Heterogeneous Radiotherapy RADIATION

High-dose radiotherapy (SBRT): 8-10 Gy × 5 fractions, administered every other day (qod), to be completed within 10 days. Low-dose radiotherapy (for other lesions): 2 Gy per fraction, one fraction per lesion.

Iparomlimab and Tuvonralimab plus Fruquintinib plus Heterogeneous Radiotherapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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%.

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.

Sponsors & Collaborators

• Huazhong University of Science and Technology: lead
• Qilu Pharmaceutical Co., Ltd.: collaborator

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

HMPL-013

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director

Study Record Dates

• First Submitted: March 20, 2026
• First Posted: March 30, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2029
• Last Updated: March 30, 2026

Record last verified: 2026-03