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

NCT07291401 | 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, single-arm, open-label, 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) received pelvic radiotherapy (36 Gy/12 fractions; adaptive boost 6 Gy/2 fractions to GTVp/GTVn permitted) with one cycle of concurrent CAPOX during the first week (oxaliplatin 100 mg/m² IV D1; capecitabine 850 mg/m² PO bid). Two weeks after radiotherapy, four cycles of immunotherapy plus chemotherapy were given (iparomlimab and tuvonralimab 5 mg/kg IV D1; oxaliplatin 130 mg/m² IV D1; capecitabine 1000 mg/m² PO bid D1-14, Q3W). Two to three weeks after immunochemotherapy, surgery was performed (TME or intersphincteric resection with sphincter preservation (ISR) ), followed by adjuvant CAPOX. The primary endpoint was pathological complete response (pCR) rate.

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 (1)

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

Interventions

lparomlimab and Tuvonralimab Injection and CPAOX and radiotherapy COMBINATION_PRODUCT

Patients received pelvic radiotherapy (36 Gy/12 fractions; adaptive boost 6 Gy/2 fractions to GTVp/GTVn permitted) with one cycle of concurrent CAPOX during the first week (oxaliplatin 100 mg/m² IV D1; capecitabine 850 mg/m² PO bid). Two weeks after radiotherapy, four cycles of immunotherapy plus chemotherapy were given (iparomlimab and tuvonralimab 5 mg/kg IV D1; oxaliplatin 130 mg/m² IV D1; capecitabine 1000 mg/m² PO bid D1-14, Q3W). Two to three weeks after immunochemotherapy, surgery was performed (TME or intersphincteric resection with sphincter preservation (ISR) ), followed by adjuvant CAPOX. The primary endpoint was pathological complete response (pCR) rate.

Group A

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

RECRUITING

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: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 5, 2025
• First Posted: December 18, 2025
• Study Start: November 1, 2025
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2029
• Last Updated: September 21, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)