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Metastatic Colorectal Cancer (CRC)Phase 2NCT07502014

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

A Phase 2 study testing Iparomlimab and Tuvonralimab (QL1706), Fruquintinib and Heterogeneous Radiotherapy in people with Metastatic Colorectal Cancer (CRC) and mCRC, run by Huazhong University of Science and Technology.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Metastatic Colorectal Cancer (CRC), mCRC
What is being tested?
Iparomlimab and Tuvonralimab (QL1706), Fruquintinib and Heterogeneous Radiotherapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
60 participants
Where
No sites listed yet
Study dates
1 May 2026to 31 Dec 2029
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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).
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  • 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.).

Who cannot join

  • 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.
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  • 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;
  • QTc interval >450 ms (males) or >470 ms (females) calculated by Fridericia formula. (If QTc is abnormal, three consecutive measurements at 2-minute intervals may be performed and averaged.)
  • Hypertension not adequately controlled by antihypertensive therapy (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg, based on average of ≥2 measurements). History of hypertensive crisis or hypertensive encephalopathy.
  • Major vascular disease within 6 months prior to initiation of study treatment (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis).
  • Severe, non-healing or dehiscent wound, active ulcer, or untreated fracture.
  • Major surgery (except diagnostic procedures) within 4 weeks prior to initiation of study treatment, or expected major surgery during the study period.
  • Inability to swallow tablets, malabsorption syndrome, or any condition impairing gastrointestinal absorption.
  • History of intestinal obstruction or clinical signs/symptoms of gastrointestinal obstruction within 6 months prior to initiation of study treatment, including partial obstruction related to underlying disease requiring parenteral hydration, parenteral nutrition, or tube feeding.
  • Patients presenting with partial obstruction, obstruction syndrome, or signs/symptoms of ileus at initial diagnosis may be enrolled if they received definitive (surgical) treatment resulting in resolution of symptoms.
  • Evidence of intra-abdominal free air not explained by recent paracentesis or surgery.
  • Metastatic disease involving major airways or vessels (e.g., complete occlusion of main portal vein or vena cava due to tumor invasion is excluded; main portal vein is defined as the confluence of splenic and superior mesenteric veins and its bifurcation into right and left intrahepatic branches) or large central mediastinal mass (<30 mm from carina).
  • History of hepatic encephalopathy.
  • Current interstitial pneumonitis or interstitial lung disease; history of interstitial pneumonitis or lung disease requiring corticosteroid treatment; pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), pneumoconiosis, drug-related pneumonitis, idiopathic pneumonia, or evidence of active pneumonitis on screening chest CT with severely impaired pulmonary function. (History of radiation pneumonitis in radiation field is permitted.) Active tuberculosis.
  • Active autoimmune disease or history of autoimmune disease with potential recurrence (including but not limited to autoimmune hepatitis, interstitial lung disease, uveitis, enteritis, hypophysitis, vasculitis, nephritis, hyperthyroidism). Patients with controlled hypothyroidism requiring only hormone replacement may be enrolled. Patients with skin diseases not requiring systemic therapy (vitiligo, psoriasis, alopecia), controlled type 1 diabetes mellitus on insulin, or childhood asthma in complete remission without adult intervention may be enrolled. Asthma requiring medical intervention with bronchodilators is excluded.
  • Use of immunosuppressive agents or systemic corticosteroids (>10 mg/day prednisone or equivalent) for immunosuppressive purposes within 14 days prior to initiation of study treatment.
  • Known severe hypersensitivity to any monoclonal antibody or anti-angiogenic targeted therapy.
  • Seere infection within 4 weeks prior to initiation of study treatment, including but not limited to hospitalization for infection, bacteremia, or severe pneumonia; therapeutic oral or intravenous antibiotics within 2 weeks prior to initiation of study treatment. (Patients receiving prophylactic antibiotics are eligible.)
  • Patients with any other conditions that, in the investigator's judgment, may affect study outcomes or lead to premature discontinuation, such as alcoholism, drug abuse, other severe comorbidities (including psychiatric disorders), significant laboratory abnormalities, or family/social issues compromising patient safety, will be excluded.

About this study

Official title: A Randomized, Parallel, Open-Label, Multicenter 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

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.

Being tested
Iparomlimab and Tuvonralimab (QL1706), Fruquintinib, Heterogeneous Radiotherapy
Medical subject headings
Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Iparomlimab and Tuvonralimab (QL1706)Drug

    Also called QL1706

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

  • FruquintinibDrug

    TKI

  • Heterogeneous RadiotherapyRadiation

    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.

Study groups in NCT07502014
Study groupRoleWhat they receive
Iparomlimab and Tuvonralimab plus Fruquintinib plus Heterogeneous RadiotherapyExperimentalFruquintinib 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.
Receives: Drug: Iparomlimab and Tuvonralimab (QL1706); Drug: Fruquintinib; Radiation: Heterogeneous Radiotherapy
Fruquintinib Administration details: 5 mg, oral administration, once daily, with a schedule of 2 weeActive comparatorFruquintinib 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.
Receives: Drug: Fruquintinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 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)

  1. Objective Response Rate (ORR)

    Defined as the proportion of patients achieving a confirmed objective tumor response (including complete response [CR] and partial response [PR]) assessed in accordance with the RECIST v1.1 criteria.

    Measured: 1 year

  2. Overall Survival (OS)

    Defined as the time from the date of a subject's enrollment to death from any cause.

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

  3. Disease Control Rate (DCR)

    Defined as the percentage of evaluable patients with a best overall response of complete response (CR), partial response (PR), or stable disease (SD) lasting for at least 8 weeks.

    Measured: 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Mar 2026
  2. Study start1 May 2026 (estimated)
  3. Primary completion31 Dec 2028 (estimated)
  4. Study completion31 Dec 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
60 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07502014
Sponsor's protocol ID
TJ-IRB202512151
Status last verified
Mar 2026
First submitted
20 Mar 2026
Last updated
30 Mar 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Iparomlimab and Tuvonralimab (QL1706), Fruquintinib and Heterogeneous Radiotherapy in people with Metastatic Colorectal Cancer (CRC) and mCRC, run by Huazhong University of Science and Technology.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 42 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 30 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-Free Survival (time frame: 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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07502014.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Mar 2026.

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