SCRT Combined With Chemotherapy and Iparomlimab and Tuvonralimab in MSS or pMMR Patients With Locally Advanced Rectal Cancer

NCT06864013 | Recruiting Phase 2 DMC

• 1 other identifier: IIT20240172C
• Study Type: interventional
• Target: 116
• Locations: 1 country
• Sites: 1

Brief Summary

Colorectal cancer ranks as the third most prevalent malignancy worldwide and the second leading cause of cancer-related mortality. For patients with locally advanced rectal cancer (LARC) classified as T3-4/N+ without distant metastasis, achieving organ preservation and functional integrity while pursuing curative treatment remains a formidable clinical challenge. This study aims to evaluate the efficacy and organ preservation rates of a novel neoadjuvant regimen comprising short-course radiotherapy followed by four cycles of CAPEOX combined with Iparomlimab and Tuvonralimab in patients with microsatellite stable (MSS) or mismatch repair proficient (pMMR) LARC. Furthermore, the project will investigate potential predictive biomarkers for complete response (CR) within this immunotherapy-based total neoadjuvant therapy (iTNT) paradigm.

Conditions

Locally Advanced Rectal Cancer (LARC)

Outcome Measures

Primary Outcomes (3)

• Complete Response

  From date of randomization until the date of treatment of surgery, assessed up to 5 months

• Clinical Complete Response

  From date of randomization until the date of discussion of multidisciplinary team, assessed up to 5 months

• Pathologic Complete Response

  From date of randomization until the date of treatment of surgery, assessed up to 5 months

Secondary Outcomes (5)

• Organ Preservation Rate

  From date of randomization until the date of treatment of additional surgery, assessed up to 100 months

• Major Pathologic Response

  From date of randomization until the date of treatment of surgery, assessed up to 5 months

• Overall Surviral

  From date of randomization until the date of death from any cause, whichever came first, assessed up to 100 months

• Desease Free Survival

  From date of randomization until the date of first documented progression, whichever came first, assessed up to 100 months

• Anal Sphincter Preservation Rate

  From date of randomization until the date of treatment of surgery, assessed up to 5 months

Study Arms (2)

Experimental Arm

EXPERIMENTAL

The experimental group will receive neoadjuvant short-course radiotherapy, followed by CAPEOX+Iparomlimab and Tuvonralimab for 4 cycles. Patients who undergo surgery will receive CAPEOX combined with Iparomlimab and Tuvonralimab for 4 cycles, followed by sequential treatment with Iparomlimab and Tuvonralimab for up to 1 year.

Drug: Experimental

Control Arm

OTHER

The control group will receive neoadjuvant short-course radiotherapy,followed by CAPEOX for 4 cycles. Patients who undergo sugery will receive CAPEOX for 4 cycles.

Drug: Control

Interventions

Experimental DRUG

The experimental group will receive neoadjuvant short-course radiotherapy (dose 25Gy/5f), followed by CAPEOX+Iparomlimab and Tuvonralimab (capecitabine 1000mg/m2 bid po d1-d14, q3w; oxaliplatin 130mg/m2 iv d1, q3w; Iparomlimab and Tuvonralimab 5mg/kg iv d1, q3w) for 4 cycles. Patients who undergo surgery will receive CAPEOX combined with Iparomlimab and Tuvonralimab for 4 cycles, followed by sequential treatment with Iparomlimab and Tuvonralimab for up to 1 year.

Experimental Arm

Control DRUG

The control group will receive neoadjuvant short-course radiotherapy,followed by CAPEOX (capecitabine 1000mg/m2 bid po d1-d14, q3w; oxaliplatin 130mg/m2 iv d1, q3w) for 4 cycles. Patients who undergo sugery will receive CAPEOX for 4 cycles.

Control Arm

Eligibility Criteria

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

You may qualify if:

• Sign a written Informed Consent Form (ICF) and be able to comply with the visits and related procedures stipulated in the protocol
• Age between 18 and 75 years old
• Histologically confirmed rectal adenocarcinoma
• According to the AJCC 8th Edition staging, imaging evaluation (enhanced CT or enhanced MRI) confirms resectable locally advanced rectal cancer (AJCC 8th Edition staging cT3-4 / cN+)
• Patients with microsatellite stability (MSS) or proficient mismatch repair (pMMR) rectal cancer
• At least one evaluable lesion according to RECIST v1.1 criteria
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 to 1
• Adequate organ and bone marrow function, defined as follows:
• Blood count: Absolute Neutrophil Count (ANC) ≥1.5×10\^9/L; Platelet (PLT) ≥100×10\^9/L; Hemoglobin (HGB) ≥10.0 g/dL.
• Liver function: Total Bilirubin (TBIL) ≤1.5×Upper Limit of Normal (ULN); Alanine transaminase (ALT) and Aspartate transaminase (AST) ≤3×ULN. Serum albumin (ALB) ≥35 g/L.
• Renal function: Serum creatinine ≤1.5×ULN or creatinine clearance ≥50 ml/min (calculated using the Cockcroft-Gault formula or standard 24-hour urine collection method); Urine dipstick test shows urine protein \<2+; For subjects with baseline urine dipstick test showing urine protein ≥2+, a 24-hour urine collection should be performed, and the protein content in the 24-hour urine should be \<1 g.
• Coagulation function: International Normalized Ratio (INR) ≤1.5, and Activated Partial Thromboplastin Time (APTT) ≤1.5×ULN. Certain anticoagulant drugs (such as antiplatelet drugs, vitamin K antagonists, etc.) need to be discontinued 7\~14 days before surgery and replaced with other drugs (such as low molecular weight heparin)
• No serious concomitant diseases that threaten the subject's survival (resulting in an expected survival time of less than 5 years)
• Female subjects of childbearing potential or male subjects with partners of childbearing potential must use effective contraception throughout the treatment period and for 6 months after the treatment period. Female subjects must have evidence of postmenopausal status or a negative urine or serum pregnancy test result for premenopausal female subjects.

You may not qualify if:

• Patients with rectal cancer who have been tested for microsatellite instability as MSI-H or mismatch repair as dMMR
• Patients who have previously received any anti-tumor treatment for the studied disease, including surgery, radiotherapy, chemotherapy, targeted therapy, immunotherapy, etc. This includes previous treatment with anti-PD-1, anti-PD-L1, anti-programmed death receptor ligand 2 (PD-L2) or anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) drugs, or any other drugs acting on T cell co-stimulation or immune checkpoint pathways (such as OX40, CD137, etc.), as well as adoptive cell immunotherapy
• Simultaneous participation in another clinical study, unless participating in an observational (non-interventional) clinical study or in the survival follow-up phase of an interventional study
• Treatment with any investigational drug or device within 4 weeks prior to the first dose of the study drug
• History of blood transfusion within 14 days before the screening laboratory tests, or use of Granulocyte-colony stimulating factor (G-CSF), Granulocyte-Macrophage-colony stimulating factor (GM-CSF), erythropoietin (EPO), thrombopoietin (TPO), or IL-11
• Use of immunosuppressive drugs within 4 weeks prior to the first dose of the study drug, excluding: intranasal inhaled local steroid therapy or local steroid injections (such as intra-articular injections); systemic corticosteroid therapy not exceeding 10 mg/day of prednisone or its equivalent physiological dose; glucocorticoids as preventive medication for allergic reactions (such as pre-CT medication); use of Chinese herbal medicine or immunomodulatory drugs with anti-tumor indications (including thymosin, interferon, interleukin, etc.) within 1 week prior to the first dose of the study drug
• Receipt of live or attenuated live vaccines within 4 weeks prior to the first dose of the study drug or expected during the study period
• Major surgical procedures (such as craniotomy, thoracotomy, or laparotomy) within 4 weeks prior to the first dose of the study drug, anticipated need for major surgery during the study treatment period (except for radical rectal cancer surgery as specified in the protocol), or presence of unhealed wounds, ulcers, or fractures
• Known active or suspected autoimmune disease or history of autoimmune disease within the past 2 years (subjects with eczema, vitiligo, psoriasis, alopecia, or Graves' disease not requiring systemic treatment in the past 2 years, history of hypothyroidism requiring only thyroid hormone replacement therapy or autoimmune hypothyroidism, and type I diabetes requiring only insulin replacement therapy may be enrolled)
• Known history of primary immunodeficiency
• Active tuberculosis, currently receiving anti-tuberculosis treatment or having received anti-tuberculosis treatment within 1 year prior to the first dose of the study drug
• Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation
• Known allergy to capecitabine, oxaliplatin, anti-PD-1 monoclonal antibody, anti-CTLA-1 monoclonal antibody, anti-PD-1/CTLA-4 antibody preparation, or other monoclonal antibody components
• Ascites and pleural effusion requiring clinical intervention in the short term, symptomatic or requiring drainage of pericardial effusion
• Human immunodeficiency virus (HIV) infection (HIV antibody positive)

Sponsors & Collaborators

• First Affiliated Hospital of Zhejiang University: lead
• Ningbo No.2 Hospital: collaborator
• Ningbo Medical Center Lihuili Hospital: collaborator
• Second Affiliated Hospital of Wenzhou Medical University: collaborator
• Ningbo No. 1 Hospital: collaborator
• The Affiliated People's Hospital of Ningbo University: collaborator
• Taizhou Hospital: collaborator

Study Sites (1)

The First Affiliated Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310006, China

RECRUITING

Study Officials

• Guosheng Wu, MD

  Zhejiang University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Guosheng Wu, MD

CONTACT

+8617857310313; guosheng_wu@zju.edu.cn

Weiqin Jiang, MD

CONTACT

+8615068117618; 1312028@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 20, 2025
• First Posted: March 7, 2025
• Study Start: January 6, 2025
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2029
• Last Updated: January 14, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)