Radiotherapy Plus CAPOX, and Iparomlimab and Tuvonralimab (QL1706) as Neoadjuvant Therapy for LARC

NCT07291401 | Not Yet Recruiting Phase 2

• 1 other identifier: 2025056
• Study Type: interventional
• Target: 108
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a single-center, prospective, randomized, double-arm, Phase II clinical trial designed to evaluate the efficacy of radiotherapy combined with CAPOX, and Iparomlimab and Tuvonralimab (QL1706) as neoadjuvant therapy for locally advanced rectal cancer. Additionally, the study seeks to explore the relationship between biomarkers in blood and tumor tissue and treatment efficacy. Eligible participants (locally advanced rectal cancer) were randomly assigned in a 1:1 ratio to two groups. Participants will: Group A patients received radiotherapy, chemotherapy, and immunotherapy. During the first week of radiotherapy, they received one cycle of CAPOX concurrent chemoradiotherapy. Two weeks after the completion of radiotherapy, they continued with four cycles of CAPOX combined with QL1706 immunotherapy. Group B patients received radiotherapy and chemotherapy. After completing the concurrent radiotherapy and chemotherapy, they rested for 2-3 weeks before completing 3 cycles of CAPOX consolidation chemotherapy. Two to three weeks after the completion of neoadjuvant therapy in groups A and B, the efficacy was evaluated, and a decision was made on whether to proceed with surgery or watchful waiting based on the efficacy.

Conditions

Rectal Cancer Patients

Outcome Measures

Primary Outcomes (1)

• Complete response (CR)

  Complete response: Pathological complete response and clinical complete response

  1 year

Secondary Outcomes (5)

• R0 Resection Rate

  1 year

• Organ Preservation Rate (OPR)

  1 year

• Disease-free survival (DFS)

  3 years

• Overall survival (OS)

  3 years

• Incidence of adverse events

  During neoadjuvant chemoradiotherapy combined with immunotherapy, an average of 6 months

Study Arms (2)

Group A

EXPERIMENTAL

Group A patients received radiotherapy, chemotherapy, and immunotherapy. During the first week of radiotherapy, they received one cycle of CAPOX concurrent chemoradiotherapy. Two weeks after the completion of radiotherapy, they continued with four cycles of CAPOX combined with QL1706 immunotherapy.

Combination Product: lparomlimab and Tuvonralimab Injection and CPAOX and radiotherapy

Group B

EXPERIMENTAL

Group B patients received radiotherapy and chemotherapy. After completing the concurrent radiotherapy and chemotherapy, they rested for 2-3 weeks before completing 3 cycles of CAPOX consolidation chemotherapy.

Combination Product: CPAOX and radiotherapy

Interventions

lparomlimab and Tuvonralimab Injection and CPAOX and radiotherapy COMBINATION_PRODUCT

Neoadjuvant chemoradiotherapy + immunotherapy: Pelvic radiotherapy (IMRT), 36 Gy/12 fractions/3 weeks; adaptive radiotherapy booster of 5-6 Gy/2 fractions is permitted for residual lesions. During the first week of radiotherapy, one cycle of CAPOX regimen concurrent chemoradiotherapy is administered (oxaliplatin, 100 mg/m2, D1, IV drip; capecitabine, 850 mg/m2, BID, oral on the day of radiotherapy). Two weeks after radiotherapy, four cycles of IT-CAPOX regimen immunotherapy combined with chemotherapy are continued (epaloliposide (QL1706) 5 mg/kg, D1, IV drip; oxaliplatin, 130 mg/m2, D1, IV drip; capecitabine, 1000 mg/m2, BID, PO, D1-14, Q3W). Two to three weeks after the completion of immunotherapy and chemotherapy, a comprehensive follow-up evaluation of efficacy is conducted, and surgical treatment is planned.

Group A

CPAOX and radiotherapy COMBINATION_PRODUCT

Neoadjuvant concurrent chemoradiotherapy: Pelvic radiotherapy, IMRT 45-50.4 Gy/25-28 F, for a total of 5-6 weeks. During radiotherapy, administer oral capecitabine concurrent chemoradiotherapy (capecitabine, 850 mg/m2, BID, orally on the day of radiotherapy). After radiotherapy, rest for 2-3 weeks, then complete 3 cycles of CAPOX consolidation chemotherapy (oxaliplatin, 130 mg/m2, D1, IV drip; capecitabine, 1000 mg/m2, BID, PO, D1-14, Q3W). 2-3 weeks after the completion of consolidation chemotherapy, conduct a comprehensive follow-up assessment of the efficacy, and surgical treatment is planned.

Group B

Eligibility Criteria

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

You may qualify if:

• (1) The patient is histologically diagnosed with rectal adenocarcinoma. (2) Age ≥18 years, \<75 years (3) Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1 (4) AJCC stage of rectal cancer: cT3-4N0M0 or TanyN1-2M0 (5) The lower margin of the rectal tumor is ≤10cm from the anus. (6) At least one evaluable lesion based on RECIST 1.1 assessment. (7) Subjects should have adequate bone marrow and liver and kidney function reserves:
• Neutrophils ≥1.5×10⁹/L, platelets ≥75×10⁹/L, and hemoglobin ≥9 g/dL
• Total bilirubin ≤1.5×Upper limit of normal (UNL); ASAT (SGOT) and/or ALAT (SGPT) ≤2.5×UNL (≤5×UNL if liver metastasis occurs); alkaline phosphatase ≤2.5×UNL (≤5×UNL if liver metastasis occurs, ≤10×UNL if bone metastasis occurs); LDH \<1500 U/L
• Creatinine clearance (calculated according to the Cockcroft and Gault formula) \>60 mL/min or serum creatinine ≤1.5×UNL; (8) Voluntarily participate in this study and sign the informed consent form

You may not qualify if:

• (1) Histopathological examination confirms the presence of other pathological types, such as squamous cell carcinoma, undifferentiated carcinoma, neuroendocrine carcinoma, etc.
• (2) Pathological examination confirms microsatellite highly unstable dMMR/msi-H (3) Presence of intestinal obstruction, intestinal perforation, bleeding, or other conditions requiring emergency surgery (4) History of pelvic radiotherapy (5) Comorbid malignant tumors (excluding cervical carcinoma in situ that has been cured for more than 2 years) (6) Receiving any other anti-tumor treatment (chemotherapy, radiotherapy, surgery, targeted therapy, immunotherapy) or participating in other new drug clinical trials within the past 4 weeks (7) Presence of the following cardiovascular and cerebrovascular diseases or risks:
• Myocardial infarction, unstable angina, cerebrovascular accident, transient ischemic attack, acute or persistent myocardial ischemia, symptomatic heart failure (Class 2 or above as determined by the New York Heart Association functional classification) within 6 months prior to randomization, symptomatic or poorly controlled arrhythmia
• years prior to first use of the drug a. History of pulmonary embolism or other serious thromboembolism within the past month
• Presence of aortic aneurysm, aortic dissection aneurysm, internal carotid artery stenosis or other major vascular diseases that may endanger life or require surgery within the past 6 months
• History of myocarditis or cardiomyopathy or current examination suggests myocarditis
• Left ventricular ejection fraction (LVEF) \<50%
• Complete left bundle branch block, third-degree atrioventricular block (8) Active autoimmune disease requiring systemic treatment within 2 years prior to the start of study treatment, or an autoimmune disease that the investigator judges may relapse or is planned for treatment. The following are excluded:
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• Skin diseases that do not require systemic treatment (e.g., vitiligo, alopecia, psoriasis, or eczema)
• Hypothyroidism caused by autoimmune thyroiditis that requires only stable doses of hormone replacement therapy
• Type I diabetes that requires only stable doses of insulin replacement therapy
• Childhood asthma that has completely resolved and requires no intervention in adulthood
• The investigator determines that the disease will not recur without external triggering factors (9) Known or suspected active pulmonary tuberculosis (10) Subjects with active hepatitis B, inactive or asymptomatic hepatitis B virus (HBV) carriers (HBsAg positive) with HBV DNA \> 500 IU/mL or \> 2500 copies/mL), and subjects with active hepatitis C should be excluded. Inactive or asymptomatic carriers of hepatitis B who are treated and stable and meet the criteria of HBV DNA ≤500 IU/mL or ≤2500 copies/mL are eligible for enrollment. Subjects with cured hepatitis C who are HCVAb positive and HCV RNA negative are eligible for enrollment. (11) Subjects who require systemic treatment with glucocorticoids (\>10 mg/day prednisone or equivalent dose) or other immunosuppressive drugs within 14 days prior to randomization. The following are exceptions:
• a. Inhaled, ophthalmic, or topical corticosteroids are permitted if there is no active autoimmune disease.

Sponsors & Collaborators

• Zhongnan Hospital: lead

Study Sites (1)

Zhongnan Hospital of Wuhan University

Wuhan, Hubei, 430071, China

Location

MeSH Terms

Interventions

Radiotherapy

Intervention Hierarchy (Ancestors)

Therapeutics

Central Study Contacts

Yongchang Wei

CONTACT

+8617771886922; weiyongchang@whu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 5, 2025
• First Posted: December 18, 2025
• Study Start: January 1, 2026
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2029
• Last Updated: December 18, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)