Radiotherapy Plus Iparomlimab and Tuvonralimab (QL1706), Regorafenib, and CAPOX as Neoadjuvant Therapy for pMMR/MSS LARC.

Recruiting now · Phase 2

Conditions studied: Rectal Cancer Patients

In brief

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.

Key facts

Study ID: NCT06911684
Run by: Sun Yat-sen University
People needed: 88
Starts: 2025-04-30
Expected to finish: 2031-12-31
Last updated by the study team: 2026-04-28

Who can join

Age: 18 and older, up to 75. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

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.
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.

You may not qualify if…

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.
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.

Where it is running

Dept. of Colorectal Surgery, Sun Yat-sen University Cancer Center. Yuexiu District, Dongfeng East Road 651 — Guangzhou, Guangdong, China (enrolling)

Full record on ClinicalTrials.gov

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