Actively Recruiting
Short-Term Radiotherapy Combined With Iparomlimab and Tuvonralimab (QL1706), Regorafenib, and CAPOX Neoadjuvant Therapy for Locally Advanced Rectal Cancer: A Multicenter, Prospective, Randomized, Phase II Clinical Trial
Led by Sun Yat-sen University · Updated on 2026-04-28
88
Participants Needed
1
Research Sites
295 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
Researchers are evaluating a new combination of treatments for adults with locally advanced rectal cancer that is proficient in mismatch repair/microsatellite stable (pMMR/MSS). This Phase II, multicenter, randomized trial compares the effects of short-term radiotherapy combined with a bispecific antibody (Iparomlimab and Tuvonralimab, also called QL1706), regorafenib, and CAPOX chemotherapy given before surgery. The study also aims to explore how various biomarkers in blood, urine, feces, and tumor tissue relate to treatment effectiveness. Participants are randomly assigned to one of two groups. Group A receives two cycles of QL1706, regorafenib, and CAPOX as induction therapy, followed by short-course radiotherapy, then four additional cycles of the same drugs. Group B starts with short-course radiotherapy and then receives six cycles of QL1706, regorafenib, and CAPOX as consolidation therapy. The radiotherapy is delivered as 25 Gy total over five sessions. After completing their assigned neoadjuvant therapies, patients are evaluated for response and then undergo surgery or watchful waiting based on results. During the study, participants will be monitored through clinical evaluations, imaging, and biomarker sample collection from blood, urine, stool, and tumor tissue. Researchers will assess outcomes such as complete response, tumor shrinkage, surgical success, and organ preservation over time. Safety and side effects will be tracked up to 30 days after treatment ends. Follow-up will continue to evaluate event-free and overall survival up to several years after therapy. Patient compliance and sample contributions are also part of the study requirements.
CONDITIONS
Brief Title
Radiotherapy Plus Iparomlimab and Tuvonralimab (QL1706), Regorafenib, and CAPOX as Neoadjuvant Therapy for pMMR/MSS LARC.
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Age between 18 and 75 years
- Histologically confirmed rectal adenocarcinoma with tumor edge 12 cm or less from the anal verge
- Clinical stage cT3-4aN0M0 or cT1-4aN+M0 by imaging
- pMMR confirmed by immunohistochemistry or MSS/MSI-L confirmed by PCR or NGS
- ECOG performance status 0-1
- Signed informed consent to participate
- No prior treatment for rectal adenocarcinoma including radiotherapy, chemotherapy, or surgery
- Planned surgery after neoadjuvant therapy
- Expected survival of at least 6 months
- Adequate organ and bone marrow function as specified
- Negative pregnancy test for women of childbearing potential and use of effective contraception
- Male participants must be surgically sterile or use contraception
- Willingness to comply with study procedures and follow-up
- Agreement to provide blood, urine, stool, and tumor tissue samples
You will not qualify if you...
- Active autoimmune disease requiring systemic treatment within 2 years, except vitiligo or resolved childhood asthma
- Use of systemic corticosteroids or immunosuppressants within 14 days before first dose
- Receipt of live vaccines within 30 days before first dose
- Use of broad-spectrum antibiotics within 30 days prior to first dose
- Prior antitumor treatments including PD-1/CTLA-4 immunotherapy or regorafenib
- Unresectable tumors or contraindications to surgery
- HIV infection or other immunodeficiency disorders
- Hepatitis B or C infection with high viral load
- Other malignancies in past 5 years except certain skin or cervical cancers
- Uncontrolled effusions requiring drainage
- Severe pulmonary diseases or impairments
- Renal failure requiring dialysis
- Active infection or fever before study treatment
- Significant cardiac conditions or poorly controlled hypertension
- Recent arterial or venous thrombosis within 6 months
- Known bleeding or clotting disorders
- Severe bleeding events within 4 weeks prior to treatment
- Tumor invasion of major blood vessels likely causing life-threatening bleeding
- Severe wounds, ulcers, or untreated fractures
- Major vascular disease or recent major surgery
- Abdominal fistula, perforation, or abscess within 6 months
- Need for long-term or high-dose NSAIDs or anticoagulants
- Known allergies or hypersensitivity to study drugs or components
- Difficulty swallowing oral study drugs
- Pregnant or breastfeeding women
- Other factors affecting safety or study integrity as judged by investigator
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - Approximately 18 weeks depending on group assignment
Participants receive short-term radiotherapy combined with immunotherapy (Iparomlimab and Tuvonralimab), regorafenib, and CAPOX chemotherapy as neoadjuvant treatment before surgery. Group A starts with induction therapy followed by radiotherapy and consolidation therapy, while Group B starts with radiotherapy followed by consolidation therapy.
Multiple treatment visits every 3 weeks during therapy cycles and radiotherapy sessions
Duration - Up to 4 weeks after neoadjuvant therapy completion
After completing neoadjuvant therapy cycles, participants undergo efficacy evaluation to determine further treatment. Options include watch-and-wait for complete responders, local excision for near complete responders, or radical surgery for partial responders or stable disease.
1 to 2 visits depending on assessment and surgery scheduling
Duration - Up to several years with safety monitoring up to 30 days after last treatment and survival follow-up up to 5 years
Participants who undergo surgery may receive additional adjuvant therapy based on investigator assessment and will be followed for safety and long-term outcomes including organ preservation and survival.
Periodic visits for up to 5 years depending on treatment and follow-up needs
Trial Site Locations
Total: 1 location
1
Dept. of Colorectal Surgery, Sun Yat-sen University Cancer Center. Yuexiu District, Dongfeng East Road 651
Guangzhou, Guangdong, China, 510060
Actively Recruiting
Research Team
K
Kai Han, M.D.
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
2
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