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

NCT06911684 | Recruiting Phase 2 DMC

• 1 other identifier: B2025-149
• Study Type: interventional
• Target: 88
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Rectal Cancer Patients

Keywords

Rectal Cancer; Neoadjuvant Therapy; pMMR/MSS; immunotherapy

Outcome Measures

Primary Outcomes (1)

• Complete response (CR)

  Complete response: Pathological complete response and clinical complete response

  Periprocedural

Secondary Outcomes (8)

• Objective response rate (ORR)

  3-4 weeks after completion of neoadjuvant therapy

• Major Pathological Response (MPR)

  During the period after the primary lesion surgery

• Tumor Regression Grade (TRG)

  During the period after the primary lesion surgery

• R0 Resection Rate

  During the period after the primary lesion surgery

• Organ Preservation Rate (OPR)

  1year after neoadjuvant therapy

Study Arms (2)

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.

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.

Combination Product: lparomlimab and Tuvonralimab Injection and regorafenib and CPAOX and short-course radiotherapy

Interventions

lparomlimab and Tuvonralimab Injection and regorafenib and CPAOX and short-course radiotherapy COMBINATION_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.

Induction chemotherapy group

Eligibility Criteria

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

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

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.

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Dept. of Colorectal Surgery, Sun Yat-sen University Cancer Center. Yuexiu District, Dongfeng East Road 651

Guangzhou, Guangdong, 510060, China

RECRUITING

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

regorafenib

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Peirong Ding M.D.

  Sun Yat-Sen University Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kai Han, M.D.

CONTACT

+8618602042643; hankai@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of the Department of Colorectal Surgery

Study Record Dates

• First Submitted: March 15, 2025
• First Posted: April 4, 2025
• Study Start: April 30, 2025
• Primary Completion: April 30, 2026
• Study Completion (Estimated): December 31, 2031
• Last Updated: April 28, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)