Rectal Cancer PatientsPhase 2NCT06911684
Radiotherapy Plus Iparomlimab and Tuvonralimab (QL1706), Regorafenib, and CAPOX as Neoadjuvant Therapy for pMMR/MSS LARC.
A Phase 2 study testing lparomlimab and Tuvonralimab Injection and regorafenib and CPAOX and short-course radiotherapy in people with Rectal Cancer Patients, run by Sun Yat-sen University at 1 site in China.
Trial summary
This study is a multicenter, prospective, randomized, double-arm, Phase II clinical trial designed to evaluate the efficacy of short-term radiotherapy combined with Iparomlimab and Tuvonralimab (QL1706), Regorafenib, and CAPOX as neoadjuvant therapy for locally advanced rectal cancer. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Rectal Cancer Patients
- What is being tested?
- lparomlimab and Tuvonralimab Injection and regorafenib and CPAOX and short-course radiotherapy
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 88 participants
- Where
- 1 siteChina
- Study dates
- 30 Apr 2025to 31 Dec 2031
- 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
- Age: 18-75 years.
- Pathology: Histologically confirmed rectal adenocarcinoma, with the lower tumor edge ≤12 cm from the anal verge.
- Initial Clinical Stage: cT3-4aN0M0 or cT1-4aN+M0, regardless of MRF, EMVI, or LLNM status.
- Preoperative staging methods: chest and abdominal CT, pelvic MRI, endoscopic ultrasound (EUS), or transrectal ultrasonography.
- pMMR/MSS Status: pMMR confirmed by immunohistochemistry (IHC) at the study center's pathology department, or MSS/MSI-L confirmed by PCR or NGS.
- ECOG Performance Status: 0-1.
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- Informed Consent: Voluntarily agrees to participate and signs the informed consent form.
- No Prior Treatment: No previous therapy targeting rectal adenocarcinoma, including radiotherapy, chemotherapy, or surgery.
- Planned Surgery: Surgery is planned upon completion of neoadjuvant therapy.
- Expected Survival: ≥6 months.
- Adequate Organ and Bone Marrow Function, meeting all of the following (with no blood products, growth factors, or other hematopoietic-supportive medications used within 14 days before first administration):
- Hematology:
- Absolute neutrophil count (ANC) ≥1.5 × 10^9/L Platelet count ≥100 × 10^9/L Hemoglobin ≥90 g/L
- Serum Biochemistry:
- Serum albumin ≥30 g/L Total bilirubin ≤1.5 × ULN ALT ≤2.5 × ULN, AST ≤2.5 × ULN Alkaline phosphatase (ALP) ≤2.5 × ULN
- Serum creatinine ≤1.5 × ULN, or creatinine clearance (CrCl) ≥50 mL/min, calculated by the Cockcroft-Gault formula:
- Contraception:
- Women of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to the first study dose, and must use effective contraception (e.g., intrauterine device, oral contraceptive, or barrier method) during the study and for at least 120 days after the final dose.
- Male participants with partners of childbearing potential must be surgically sterile or must agree to use effective contraception during the study and for 120 days after the final dose.
- Compliance and Follow-up: Demonstrates good compliance and agrees to attend follow-up visits.
- Biological Samples: Agrees to provide blood, urine, stool, and tumor tissue samples.
Who cannot join
- Active Autoimmune Disease: Any active autoimmune disease requiring systemic treatment (i.e., disease-modifying medications, corticosteroids, or immunosuppressive agents) within 2 years prior to enrollment (e.g., myasthenia gravis, systemic lupus erythematosus, interstitial pneumonitis, uveitis, ulcerative colitis, autoimmune hepatitis, hypophysitis, systemic vasculitis, nephritis, hyperthyroidism, hypothyroidism, mixed connective tissue disease).
- Exceptions: vitiligo, or childhood asthma that has fully resolved in adulthood without therapy.
- Asthma requiring bronchodilator therapy is ineligible. Physiologic replacement therapy (e.g., thyroid hormone, insulin, or low-dose steroids for adrenal/pituitary insufficiency) is not considered systemic treatment.
- Concurrent Systemic Therapy: Use of systemic corticosteroids (≥10 mg/day of prednisone or equivalent) or other immunosuppressants (e.g., cyclosporine, cyclophosphamide, azathioprine, methotrexate, thalidomide) within 14 days before the first dose, or use of immunostimulants (e.g., interferon, interleukin-2) within 4 weeks before the first dose.
- Live Vaccines: Receipt of a live or attenuated live vaccine within 30 days before the first dose or potentially during the study period.
- Antibiotic Use: Administration of broad-spectrum antibiotics by any route within 30 days prior to the first dose.
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- Previous Anticancer Therapies: Any prior antitumor treatments (radiotherapy, chemotherapy, surgery [excluding biopsy], PD-1/CTLA-4 dual immunotherapy, regorafenib, or other tyrosine kinase inhibitors).
- Unresectable Factors: Tumors deemed unresectable or participants with surgical contraindications, or who refuse surgery.
- Immunodeficiency: HIV infection, any other acquired or congenital immunodeficiency disorder, or a history of organ or allogeneic bone marrow transplantation (excluding corneal transplantation).
- Hepatitis B/C Co-infection:
- HBsAg-positive and/or HBcAb-positive with HBV DNA >10^4 copies/mL (≈2000 IU/mL).
- Anti-HCV antibody-positive with HCV-RNA >10^3 copies/mL. Patients positive for both HBsAg and HCV-RNA are excluded.
- Other Malignancies: Any other malignancies within the past 5 years or concurrent malignancies, except for treated basal cell carcinoma of the skin or carcinoma in situ of the cervix.
- Uncontrolled Effusions: Uncontrolled pleural effusion, pericardial effusion, or ascites requiring drainage.
- Severe Pulmonary Conditions: Known active pulmonary tuberculosis, radiation pneumonitis, drug-induced pneumonitis, or other severe pulmonary diseases/impairments.
- Renal Failure: Renal failure requiring hemodialysis or peritoneal dialysis.
- Active Infection or Fever: Active infection, unexplained fever ≥38.5°C within 7 days prior to study treatment, or baseline WBC count >15 × 10^9/L.
- Cardiac Conditions: Poorly controlled or clinically significant cardiac conditions, including:
- NYHA Class II or higher heart failure, LVEF <50% Unstable angina Myocardial infarction within 1 year prior to randomization Clinically significant arrhythmias requiring treatment or intervention QTc >450 ms (men), or QTc >470 ms (women)
- Hypertension: Poorly controlled (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg) despite antihypertensive therapy, or a history of hypertensive crisis/encephalopathy.
- Recent Thrombosis: Arterial or venous thrombosis within 6 months prior to enrollment (e.g., stroke, transient ischemic attack, cerebral hemorrhage, cerebral infarction, deep vein thrombosis, pulmonary embolism).
- Coagulopathy: Known hereditary or acquired bleeding/thrombotic disorders (e.g., hemophilia, coagulopathy).
- Significant Bleeding: Evidence or history of bleeding. Any Grade ≥3 hemorrhage within 4 weeks prior to study treatment (per CTCAE v5.0).
- Vascular Invasion: Tumor invasion of major blood vessels or a high likelihood thereof during the study, potentially leading to life-threatening bleeding as judged by imaging.
- Wounds or Ulcers: Severe, unhealed or dehiscent wounds, active ulcers, or untreated fractures.
- Major Vascular Disease: Major vascular disorders within 6 months prior to study treatment (e.g., requiring surgical repair for an aneurysm or recent peripheral arterial thrombosis).
- Major Surgery: Major surgery (other than diagnostic) within 4 weeks prior to study treatment, or planned major surgery during the study period (excluding the planned study-related procedure).
- Abdominal Fistula, Perforation, or Abscess: Such events within 6 months prior to study treatment.
- Long-Term NSAIDs or Anticoagulants: Need for long-term or high-dose NSAIDs (≥325 mg aspirin) or anticoagulant therapy.
- Known Drug Allergy: Suspected or known allergy to any study drug or its components relevant to this trial.
- Monoclonal Antibody Hypersensitivity: History of severe hypersensitivity reactions to any monoclonal antibody, or known hypersensitivity/allergy to QL1706, regorafenib, oxaliplatin, capecitabine, or any of their components.
- Difficulty Swallowing: Inability or difficulty swallowing oral study drugs.
- Pregnant or Breastfeeding: Women who are pregnant or lactating.
- Other Factors: Any other factors that may affect study outcomes or lead to premature termination, including a history of alcohol or drug abuse, severe diseases (including psychiatric disorders) requiring combination treatment, significant laboratory abnormalities, or family/social circumstances that, in the investigator's judgment, compromise patient safety or study integrity.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Dept. of Colorectal Surgery, Sun Yat-sen University Cancer Center. Yuexiu District, Dongfeng East Road 651
Guangzhou, Guangdong, 510060
Kai Han, M.D., +86-18602042643, hankai@sysucc.org.cn
Peirong Ding, M.D.
About this study
Official title: 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
This study is a multicenter, prospective, randomized, double-arm, Phase II clinical trial designed to evaluate the efficacy of short-term radiotherapy combined with Iparomlimab and Tuvonralimab (QL1706), Regorafenib, and CAPOX as neoadjuvant therapy for locally advanced rectal cancer. Additionally, the study seeks to explore the relationship between biomarkers in blood, urine, feces, and tumor tissue and treatment efficacy.
Eligible participants (pMMR/MSS locally advanced rectal cancer) were randomly assigned in a 1:1 ratio to two groups, with randomization stratified by MRF (+ vs. -).
Read more
Participants will:
- Group A patients received two cycles of QL1706, regorafenib, and CAPOX induction therapy, followed by sequential short-course radiotherapy, and then continued with four cycles of QL1706, regorafenib, and CAPOX consolidation therapy.
- Group B patients received short-course radiotherapy followed by six cycles of QL1706, regorafenib, and CAPOX consolidation therapy.
After two cycles of neoadjuvant therapy in Group A and six cycles in Group B, efficacy was evaluated and decisions regarding surgery or watchful waiting were made based on efficacy.
Read the detailed description
Colorectal cancer (CRC) is the third most common malignancy worldwide. The standard treatment for locally advanced rectal cancer (LARC) includes neoadjuvant chemoradiotherapy, total mesorectal excision (TME), and postoperative adjuvant chemotherapy. However, distant metastasis and postoperative complications remain major challenges. Total neoadjuvant therapy (TNT), by advancing adjuvant chemotherapy to the neoadjuvant phase, has significantly improved patient compliance and tumor response rates. The MSKCC study demonstrated a tumor response rate of up to 90% under the TNT regimen, with 30% of patients achieving pathological or clinical complete response (pCR or cCR). The TIMING trial further confirmed that TNT significantly increased the pCR rate without increasing side effects or surgical complications.
Immunotherapy has shown significant efficacy in dMMR/MSI-H CRC. The NICHE study demonstrated that dual immunotherapy achieved 100% pathological response in dMMR colorectal cancer patients. However, pMMR/MSS CRC is not sensitive to immunotherapy, but some patients may still benefit from combined anti-angiogenesis agents (such as regorafenib) or CTLA-4 antibodies. The REGONIVO study showed an objective response rate (ORR) of 36.0% in pMMR/MSS CRC patients, while the RIN study further increased the ORR to 27.6%.
Radiotherapy combined with immunotherapy has emerged as a new treatment modality for LARC. The UNION study found that short-term radiotherapy followed by sequential PD-1 antibody and CAPOX chemotherapy increased the pCR rate to 39.8%. The TORCH study explored the effectiveness of short-term radiotherapy combined with PD-1 antibody and CAPOX chemotherapy, achieving a CR rate of over 50%. The REGINA study went further, using short-term radiotherapy combined with regorafenib and nivolumab, achieving a CR rate of 44.4%.
Iparomlimab and Tuvonralimab (QL1706) is a bispecific antibody targeting PD-1 and CTLA-4, enhancing T cell activation and anti-tumor response through synergistic effects. In September 2024, QL1706 was approved for the treatment of recurrent or metastatic cervical cancer. Based on existing studies, short-term radiotherapy combined with immunotherapy (PD-1 antibody, CTLA-4 antibody), regorafenib, and CAPOX chemotherapy may significantly improve efficacy in pMMR/MSS LARC patients, warranting further exploration of its safety and effectiveness.
Eligible participants (pMMR/MSS locally advanced rectal cancer) were randomly assigned in a 1:1 ratio to two groups, with randomization stratified by MRF (+ vs. -). Group A patients received two cycles of QL1706, regorafenib, and CAPOX induction therapy, followed by sequential short-course radiotherapy, and then continued with four cycles of QL1706, regorafenib, and CAPOX consolidation therapy. Group B patients received short-course radiotherapy followed by six cycles of QL1706, regorafenib, and CAPOX consolidation therapy. After two cycles of neoadjuvant therapy in Group A and six cycles in Group B, efficacy was evaluated and decisions regarding surgery or watchful waiting were made based on efficacy. Postoperative need for adjuvant therapy was determined by the investigator.
Efficacy assessment: Patients achieving clinical complete response (cCR) could undergo a watch-and-wait strategy; patients with near cCR could undergo transanal local excision; patients with partial response (PR) or stable disease (SD) would undergo radical surgery. The need for postoperative adjuvant therapy was determined by the investigator. Patients with local progressive disease (PD) or distant metastasis were treated according to current guidelines.
- Conditions
- Rectal Cancer Patients
- Being tested
- lparomlimab and Tuvonralimab Injection and regorafenib and CPAOX and short-course radiotherapy
- Keywords
- Rectal Cancer, Neoadjuvant Therapy, pMMR/MSS, immunotherapy
- Medical subject headings
- Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
lparomlimab and Tuvonralimab Injection and regorafenib and CPAOX and short-course radiotherapyCombination product
Group A patients received two cycles of QL1706, regorafenib, and CAPOX induction therapy, followed by sequential short-course radiotherapy, and then continued with four cycles of QL1706, regorafenib, and CAPOX consolidation therapy.
lparomlimab and Tuvonralimab Injection(QL1706): 5 mg/kg, intravenous (IV), on Day 1, every 3 weeks (q3w) during the neoadjuvant treatment phase.
Regorafenib:80 mg, oral (PO), once daily (qd), Days 1-14, every 3 weeks (q3w) during the neoadjuvant treatment phase.
CAPOX: Oxaliplatin( 130 mg/m², IV over 2 hours, Day 1, every 3 weeks (q3w))+ Capecitabine( 1000 mg/m², PO, twice daily (bid), Days 1-14, every 3 weeks (q3w)).
Short-course radiotherapy:The total dosage was 25Gy consisted of 5 fractions of 5 Gy to clinical target volume without a boost dose.
lparomlimab and Tuvonralimab Injection and regorafenib and CPAOX and short-course radiotherapyCombination product
Group B patients received short-course radiotherapy followed by six cycles of QL1706, regorafenib, and CAPOX consolidation therapy.
lparomlimab and Tuvonralimab Injection(QL1706): 5 mg/kg, intravenous (IV), on Day 1, every 3 weeks (q3w) during the neoadjuvant treatment phase. Regorafenib:80 mg, oral (PO), once daily (qd), Days 1-14, every 3 weeks (q3w) during the neoadjuvant treatment phase. CAPOX: Oxaliplatin( 130 mg/m², IV over 2 hours, Day 1, every 3 weeks (q3w))+ Capecitabine( 1000 mg/m², PO, twice daily (bid), Days 1-14, every 3 weeks (q3w)). Short-course radiotherapy:The total dosage was 25Gy consisted of 5 fractions of 5 Gy to clinical target volume without a boost dose.
| Study group | Role | What they receive |
|---|---|---|
| Induction chemotherapy group | Experimental | Group A patients received two cycles of QL1706, regorafenib, and CAPOX induction therapy, followed by sequential short-course radiotherapy, and then continued with four cycles of QL1706, regorafenib, and CAPOX consolidation therapy. Receives: Combination Product: lparomlimab and Tuvonralimab Injection and regorafenib and CPAOX and short-course radiotherapy |
| Consolidation chemotherapy group | Experimental | Group B patients received short-course radiotherapy followed by six cycles of QL1706, regorafenib, and CAPOX consolidation therapy. Receives: Combination Product: lparomlimab and Tuvonralimab Injection and regorafenib and CPAOX and short-course radiotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete response (CR)
Complete response: Pathological complete response and clinical complete response
Measured: Periprocedural
Secondary outcomes (8)
Objective response rate (ORR)
The proportion of patients achieving a complete response (CR) or partial response (PR), evaluated according to RECIST v1.1.
Measured: 3-4 weeks after completion of neoadjuvant therapy
Major Pathological Response (MPR)
The proportion of patients whose primary tumor shows ≤10% residual tumor cells on pathology.
Measured: During the period after the primary lesion surgery
Tumor Regression Grade (TRG)
Assessed based on the 8th edition of the AJCC staging system to grade the extent of tumor regression
Measured: During the period after the primary lesion surgery
R0 Resection Rate
The proportion of surgical patients who achieve an R0 resection. R0 resection: All gross disease has been removed, and microscopic examination reveals all surgical margins free of tumor.
Measured: During the period after the primary lesion surgery
Organ Preservation Rate (OPR)
The 1-year organ preservation rate is the percentage of patients attaining a complete clinical response (cCR) or near-complete clinical response (near-cCR) following neoadjuvant therapy, who then proceeded with non-surgical management or local excision, was monitored under a Watch \& Wait strategy or for 1 year post-local resection without undergoing radical surgery.
Measured: 1year after neoadjuvant therapy
Event-free survival (EFS)
EFS is defined as the time from randomization to the earliest occurrence of any of the following events:
Tumor progression by imaging according to RECIST 1.1, Tumor recurrence (local or distant), confirmed by imaging or biopsy, for patients with no residual tumor after surgery, Death from any cause. Note: A second primary malignancy is not considered an EFS event.
Measured: 2 years
Overall survival (OS)
The time interval between the date of randomization to the date of death. If the patient has been alive, the time until the last follow-up is taken as the overall survival period.
Measured: 5 years
Incidence of adverse events
Assessed by Common Terminology Criteria for Adverse Events version 4.0. The overall adverse event rates and the immune-related adverse event rates will be compared between treatment arms using Chi-square test or Fisher's exact test, as appropriate.
Measured: up to 30 days after last treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Apr 2025
- Study start30 Apr 2025
- Primary completion30 Apr 2026 (estimated)
- Study completion31 Dec 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Rectal Cancer PatientsStudies of the same condition, open and under way.
- More trials run by Sun Yat-sen UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 88 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sun Yat-sen University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Pei-Rong Ding, Sun Yat-sen University
- Investigators
- Peirong Ding M.D., Principal investigator, Sun Yat-Sen University Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06911684
- Sponsor's protocol ID
- B2025-149
- Status last verified
- Apr 2026
- First submitted
- 15 Mar 2025
- Last updated
- 28 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT06911684
- Acronym / sponsor ID
- B2025-149
- Conditions
- Rectal Cancer Patients
- Keywords
- Rectal Cancer, Neoadjuvant Therapy, pMMR/MSS, immunotherapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 88 participants (estimated)
- Lead sponsor
- Sun Yat-sen UniversityUniversity, hospital or other
- Study start
- 30 Apr 2025 (actual)
- Primary completion
- 30 Apr 2026 (estimated)
- Study completion
- 31 Dec 2031 (estimated)
- First posted
- 4 Apr 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is a multicenter, prospective, randomized, double-arm, Phase II clinical trial designed to evaluate the efficacy of short-term radiotherapy combined with Iparomlimab and Tuvonralimab (QL1706), Regorafenib, and CAPOX as neoadjuvant therapy for locally advanced rectal cancer. Additionally, the study seeks to explore the relationship between biomarkers in blood, urine, feces, and tumor tissue and treatment efficacy.
Eligible participants (pMMR/MSS locally advanced rectal cancer) were randomly assigned in a 1:1 ratio to two groups, with randomization stratified by MRF (+ vs. -).
Participants will:
- Group A patients received two cycles of QL1706, regorafenib, and CAPOX induction therapy, followed by sequential short-course radiotherapy, and then continued with four cycles of QL1706, regorafenib, and CAPOX consolidation therapy.
- Group B patients received short-course radiotherapy followed by six cycles of QL1706, regorafenib, and CAPOX consolidation therapy.
After two cycles of neoadjuvant therapy in Group A and six cycles in Group B, efficacy was evaluated and decisions regarding surgery or watchful waiting were made based on efficacy.
Detailed description
Colorectal cancer (CRC) is the third most common malignancy worldwide. The standard treatment for locally advanced rectal cancer (LARC) includes neoadjuvant chemoradiotherapy, total mesorectal excision (TME), and postoperative adjuvant chemotherapy. However, distant metastasis and postoperative complications remain major challenges. Total neoadjuvant therapy (TNT), by advancing adjuvant chemotherapy to the neoadjuvant phase, has significantly improved patient compliance and tumor response rates. The MSKCC study demonstrated a tumor response rate of up to 90% under the TNT regimen, with 30% of patients achieving pathological or clinical complete response (pCR or cCR). The TIMING trial further confirmed that TNT significantly increased the pCR rate without increasing side effects or surgical complications.
Immunotherapy has shown significant efficacy in dMMR/MSI-H CRC. The NICHE study demonstrated that dual immunotherapy achieved 100% pathological response in dMMR colorectal cancer patients. However, pMMR/MSS CRC is not sensitive to immunotherapy, but some patients may still benefit from combined anti-angiogenesis agents (such as regorafenib) or CTLA-4 antibodies. The REGONIVO study showed an objective response rate (ORR) of 36.0% in pMMR/MSS CRC patients, while the RIN study further increased the ORR to 27.6%.
Radiotherapy combined with immunotherapy has emerged as a new treatment modality for LARC. The UNION study found that short-term radiotherapy followed by sequential PD-1 antibody and CAPOX chemotherapy increased the pCR rate to 39.8%. The TORCH study explored the effectiveness of short-term radiotherapy combined with PD-1 antibody and CAPOX chemotherapy, achieving a CR rate of over 50%. The REGINA study went further, using short-term radiotherapy combined with regorafenib and nivolumab, achieving a CR rate of 44.4%.
Iparomlimab and Tuvonralimab (QL1706) is a bispecific antibody targeting PD-1 and CTLA-4, enhancing T cell activation and anti-tumor response through synergistic effects. In September 2024, QL1706 was approved for the treatment of recurrent or metastatic cervical cancer. Based on existing studies, short-term radiotherapy combined with immunotherapy (PD-1 antibody, CTLA-4 antibody), regorafenib, and CAPOX chemotherapy may significantly improve efficacy in pMMR/MSS LARC patients, warranting further exploration of its safety and effectiveness.
Eligible participants (pMMR/MSS locally advanced rectal cancer) were randomly assigned in a 1:1 ratio to two groups, with randomization stratified by MRF (+ vs. -). Group A patients received two cycles of QL1706, regorafenib, and CAPOX induction therapy, followed by sequential short-course radiotherapy, and then continued with four cycles of QL1706, regorafenib, and CAPOX consolidation therapy. Group B patients received short-course radiotherapy followed by six cycles of QL1706, regorafenib, and CAPOX consolidation therapy. After two cycles of neoadjuvant therapy in Group A and six cycles in Group B, efficacy was evaluated and decisions regarding surgery or watchful waiting were made based on efficacy. Postoperative need for adjuvant therapy was determined by the investigator.
Efficacy assessment: Patients achieving clinical complete response (cCR) could undergo a watch-and-wait strategy; patients with near cCR could undergo transanal local excision; patients with partial response (PR) or stable disease (SD) would undergo radical surgery. The need for postoperative adjuvant therapy was determined by the investigator. Patients with local progressive disease (PD) or distant metastasis were treated according to current guidelines.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Induction chemotherapy group | Experimental | Combination Product: lparomlimab and Tuvonralimab Injection and regorafenib and CPAOX and short-course radiotherapyGroup A patients received two cycles of QL1706, regorafenib, and CAPOX induction therapy, followed by sequential short-course radiotherapy, and then continued with four cycles of QL1706, regorafenib, and CAPOX consolidation therapy. |
| Consolidation chemotherapy group | Experimental | Combination Product: lparomlimab and Tuvonralimab Injection and regorafenib and CPAOX and short-course radiotherapyGroup B patients received short-course radiotherapy followed by six cycles of QL1706, regorafenib, and CAPOX consolidation therapy. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Age: 18-75 years.
- Pathology: Histologically confirmed rectal adenocarcinoma, with the lower tumor edge ≤12 cm from the anal verge.
- Initial Clinical Stage: cT3-4aN0M0 or cT1-4aN+M0, regardless of MRF, EMVI, or LLNM status.
- Preoperative staging methods: chest and abdominal CT, pelvic MRI, endoscopic ultrasound (EUS), or transrectal ultrasonography.
- pMMR/MSS Status: pMMR confirmed by immunohistochemistry (IHC) at the study center's pathology department, or MSS/MSI-L confirmed by PCR or NGS.
Key exclusion criteria (34 listed)
- Active Autoimmune Disease: Any active autoimmune disease requiring systemic treatment (i.e., disease-modifying medications, corticosteroids, or immunosuppressive agents) within 2 years prior to enrollment (e.g., myasthenia gravis, systemic lupus erythematosus, interstitial pneumonitis, uveitis, ulcerative colitis, autoimmune hepatitis, hypophysitis, systemic vasculitis, nephritis, hyperthyroidism, hypothyroidism, mixed connective tissue disease).
- Exceptions: vitiligo, or childhood asthma that has fully resolved in adulthood without therapy.
- Asthma requiring bronchodilator therapy is ineligible. Physiologic replacement therapy (e.g., thyroid hormone, insulin, or low-dose steroids for adrenal/pituitary insufficiency) is not considered systemic treatment.
- Concurrent Systemic Therapy: Use of systemic corticosteroids (≥10 mg/day of prednisone or equivalent) or other immunosuppressants (e.g., cyclosporine, cyclophosphamide, azathioprine, methotrexate, thalidomide) within 14 days before the first dose, or use of immunostimulants (e.g., interferon, interleukin-2) within 4 weeks before the first dose.
- Live Vaccines: Receipt of a live or attenuated live vaccine within 30 days before the first dose or potentially during the study period.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| lparomlimab and Tuvonralimab Injection and regorafenib and CPAOX and short-course radiotherapyGroup A patients received two cycles of QL1706, regorafenib, and CAPOX induction therapy, followed by sequential short-course radiotherapy, and then continued with four cycles of QL1706, regorafenib, and CAPOX consolidation therapy. lparomlimab and Tuvonralimab Injection(QL1706): 5 mg/kg, intravenous (IV), on Day 1, every 3 weeks (q3w) during the neoadjuvant treatment phase. Regorafenib:80 mg, oral (PO), once daily (qd), Days 1-14, every 3 weeks (q3w) during the neoadjuvant treatment phase. CAPOX: Oxaliplatin( 130 mg/m², IV over 2 hours, Day 1, every 3 weeks (q3w))+ Capecitabine( 1000 mg/m², PO, twice daily (bid), Days 1-14, every 3 weeks (q3w)). Short-course radiotherapy:The total dosage was 25Gy consisted of 5 fractions of 5 Gy to clinical target volume without a boost dose. | Combination product | Induction chemotherapy group |
| lparomlimab and Tuvonralimab Injection and regorafenib and CPAOX and short-course radiotherapyGroup B patients received short-course radiotherapy followed by six cycles of QL1706, regorafenib, and CAPOX consolidation therapy. lparomlimab and Tuvonralimab Injection(QL1706): 5 mg/kg, intravenous (IV), on Day 1, every 3 weeks (q3w) during the neoadjuvant treatment phase. Regorafenib:80 mg, oral (PO), once daily (qd), Days 1-14, every 3 weeks (q3w) during the neoadjuvant treatment phase. CAPOX: Oxaliplatin( 130 mg/m², IV over 2 hours, Day 1, every 3 weeks (q3w))+ Capecitabine( 1000 mg/m², PO, twice daily (bid), Days 1-14, every 3 weeks (q3w)). Short-course radiotherapy:The total dosage was 25Gy consisted of 5 fractions of 5 Gy to clinical target volume without a boost dose. | Combination product | Consolidation chemotherapy group |
Primary outcome
Complete response (CR)
Time frame: Periprocedural
Complete response: Pathological complete response and clinical complete response
8 secondary outcomes
Objective response rate (ORR)
Time frame: 3-4 weeks after completion of neoadjuvant therapy
Major Pathological Response (MPR)
Time frame: During the period after the primary lesion surgery
Tumor Regression Grade (TRG)
Time frame: During the period after the primary lesion surgery
R0 Resection Rate
Time frame: During the period after the primary lesion surgery
Organ Preservation Rate (OPR)
Time frame: 1year after neoadjuvant therapy
Event-free survival (EFS)
Time frame: 2 years
Overall survival (OS)
Time frame: 5 years
Incidence of adverse events
Time frame: up to 30 days after last treatment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Apr 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Peirong Ding M.D. principal investigator
Sun Yat-Sen University Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing lparomlimab and Tuvonralimab Injection and regorafenib and CPAOX and short-course radiotherapy in people with Rectal Cancer Patients, run by Sun Yat-sen University at 1 site in China.
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 21 inclusion and 34 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: looking for participants now, as of the sponsor's last update on 28 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
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?
Contact Kai Han, M.D. (+8618602042643, hankai@sysucc.org.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Complete response (CR) (time frame: Periprocedural). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 28 Apr 2026.