Iparomlimab and Tuvonralimab Combined With Chemotherapy and Bevacizumab as Neoadjuvant Therapy for Locally Advanced Rectal Cancer

NCT07769853 | Not Yet Recruiting

• 1 other identifier: IT-CABLE QL-1706
• Study Type: interventional
• Target: 56
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study aims to observe and evaluate the efficacy and safety of Iparomlimab and Tuvonralimab（QL-1706） combined with chemotherapy and bevacizumab ± radiotherapy as neoadjuvant therapy in patients with locally advanced rectal cancer, and to explore the value and implications of radiotherapy omission in this setting.

Conditions

Locally Advanced Rectal Cancer (LARC); 5-12cm to Anal Verge

Outcome Measures

Primary Outcomes (2)

• Clinical Complete Response (CCR)

  absence of detectable tumor on clinical, radiological, endoscopic, and digital rectal examination

  3 weeks After last round of neoadjuvant treatment

• Pathological Complete Response (pCR)

  Pathological Complete Response means no residual viable tumor cells in the surgical specimen, including both the primary tumor site and regional lymph nodes, after neoadjuvant therapy and surgery.

  1 month after surgery

Secondary Outcomes (5)

• surgery complications

  up to 6 weeks after surgery

• 3-year disease-free survival

  3 years after surgery

• 3-year Event-Free Survival (EFS)

  3 years after surgery

• Adverse Effects

  3 months after surgery

• Quality of Life Score

  3 years after surgery

Study Arms (1)

Experimental group

EXPERIMENTAL

Drug: Iparomlimab and Tuvonralimab（QL-1706）combined with Chemotherapy and Bevacizumab

Interventions

Iparomlimab and Tuvonralimab（QL-1706）combined with Chemotherapy and Bevacizumab DRUG

The QL1706 dosage is 5 mg/kg, administered via intravenous infusion once every 3 weeks, for a total of 4 doses, or until intolerable toxicity occurs or the subject withdraws informed consent. The bevacizumab injection dosage is 7.5 mg/kg, administered via intravenous infusion once every 3 weeks, for a total of 4 doses, or until intolerable toxicity occurs or the subject withdraws informed consent. Within 21 days after completing the 4th cycle of adjuvant treatment, the patient will be evaluated to determine whether additional radiotherapy would be required before surgery.

Also known as: Radiotherapy, Surgery

Experimental group

Eligibility Criteria

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

You may qualify if:

• The patient voluntarily consents to participate in this study, demonstrates good compliance, is able to meet the trial requirements for observation and follow-up, and has signed the informed consent form;
• Age between 18 and 75 years, inclusive, regardless of gender (at the time of signing the informed consent);
• ECOG Performance Status (PS) score of 0 or 1;
• Expected survival time ≥12 weeks;
• Histologically confirmed diagnosis of mid- or upper-rectal adenocarcinoma, with the tumor located 5-12 cm from the anal verge;
• Colonoscopic biopsy specimens assessed by the pathology department at the study center show pMMR by immunohistochemistry or MSS by genetic testing (PCR or NGS method);
• Clinical staging of cT3-4N0M0 or cTxN+M0;
• No prior anti-tumor therapy (including but not limited to radiotherapy, chemotherapy, targeted therapy, or immunotherapy);
• At least one measurable lesion: the lesion must have one clearly measurable diameter (recorded as the longest diameter), with the minimum size defined as follows:
• CT scan: ≥10 mm (CT slice thickness should not exceed 5 mm);
• Malignant lymph nodes: must be pathologically enlarged and measurable, with a short-axis diameter of ≥15 mm on CT (recommended slice thickness ≤5 mm);
• Major organ functions must be adequate, meeting the following criteria:
• Hematology (without hematopoietic growth factors or blood transfusion within 7 days):
• Neutrophils ≥1.5 × 10⁹/L
• Platelets ≥100 × 10⁹/L

You may not qualify if:

• Clinical stage cT4b and low rectal cancer (tumor located less than 5 cm from the anal verge);
• Prior rectal cancer surgery before enrollment, excluding stoma procedures;
• History of malignancy, except for cured carcinoma in situ of the cervix, basal cell or squamous cell carcinoma of the skin, superficial bladder cancer, or early-stage thyroid cancer;
• Severe hypersensitivity or allergic reactions to humanized antibodies or fusion proteins in the past;
• Pregnant or breastfeeding women, or women of childbearing potential who are not using contraception;
• Diagnosed immunodeficiency or receiving systemic glucocorticoids or other immunosuppressive therapy within 14 days prior to the first dose of study treatment. Physiological doses of glucocorticoids (≤10 mg/day prednisone or equivalent) are allowed;
• Active, known, or suspected autoimmune diseases (e.g., interstitial pneumonia, colitis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism, etc.) are excluded. However, patients with type 1 diabetes, hypothyroidism requiring only hormone replacement therapy, or skin conditions not requiring systemic treatment (e.g., vitiligo, psoriasis, or alopecia), or conditions not expected to recur without an external trigger, may be enrolled;
• Severe pre-existing cardiac conditions, including: congestive heart failure, uncontrolled high-risk arrhythmias, unstable angina, myocardial infarction, or severe valvular heart disease;
• Hypertension that is poorly controlled with antihypertensive medication (systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg). Patients are eligible if BP is well controlled with treatment. Patients with a history of hypertensive crisis or hypertensive encephalopathy are excluded;
• Active hepatitis B (HBV DNA ≥2000 IU/ml or 10⁴ copies/ml) or hepatitis C (positive anti-HCV antibody and HCV-RNA above detection threshold);
• Active tuberculosis (TB) infection, as determined by chest X-ray, sputum test, and clinical examination. Patients with a history of active TB infection within the past year are excluded even if treated. Those with TB infection more than a year ago are also excluded unless prior anti-TB treatment was appropriate in both duration and regimen;
• Major surgery, incisional biopsy, or significant traumatic injury within 28 days prior to randomization;
• Imaging indicates tumor invasion of major blood vessels, or in the investigator's opinion, the tumor is likely to invade major blood vessels during the study and pose a risk of fatal hemorrhage;
• Any signs or history of bleeding disorders, regardless of severity; patients who had any bleeding event ≥ Grade 3 (CTCAE) within 4 weeks prior to randomization; patients with unhealed wounds, ulcers, or fractures;
• Arterial or venous thrombotic events (e.g., stroke, transient ischemic attack, deep vein thrombosis, or pulmonary embolism) within the past 6 months;

Sponsors & Collaborators

• Zhejiang University: lead

MeSH Terms

Interventions

Drug Therapy; Bevacizumab; Radiotherapy; Surgical Procedures, Operative

Intervention Hierarchy (Ancestors)

Therapeutics; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 2, 2025
• First Posted: August 18, 2026
• Study Start: September 1, 2026
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): December 12, 2029
• Last Updated: September 15, 2026

Record last verified: 2026-08