Immunotherapy, Local Advanced Rectal Cancer, Radiotherapy
Conditions
Keywords
local advanced rectal cancer, radiotherapy, immunotherapy
Brief summary
This multicenter, randomized, controlled, phase III trial evaluates whether adding iparomlimab and tuvonralimab injection to CAPOX consolidation chemotherapy after short-course radiotherapy improves tumor response in patients with treatment-naive, proficient mismatch repair/microsatellite-stable (pMMR/MSS) locally advanced rectal adenocarcinoma. Eligible patients will be randomly assigned in a 1:1 ratio to receive short-course radiotherapy followed by CAPOX plus iparomlimab and tuvonralimab, or short-course radiotherapy followed by CAPOX alone. After total neoadjuvant therapy, patients with a clinical complete response may undergo a Watch-and-Wait strategy, whereas other patients will undergo total mesorectal excision according to standard clinical practice. The primary endpoint is complete response rate, defined as pathologic complete response after surgery or clinical complete response sustained for more than 1 year. Secondary endpoints include 3-year relapse-free survival, 3-year overall survival, sphincter preservation rate, and grade 3-4 acute adverse events. Exploratory analyses will assess tissue and blood biomarkers associated with treatment response.
Interventions
RADIATIONShort-Course Radiotherapy
Short-course external-beam radiotherapy will be delivered to the rectal primary tumor and corresponding lymphatic drainage regions using IMRT or VMAT. The prescribed dose is 25 Gy in 5 fractions over 1 week. No concurrent chemotherapy will be administered during short-course radiotherapy.
DRUGConsolidation treatment (With ICIs)
Iparomlimab and tuvonralimab injection will be administered at 5 mg/kg by intravenous infusion every 21 days for 6 cycles. CAPOX chemotherapy will consist of oxaliplatin 130 mg/m² intravenously on day 1 plus capecitabine 1000 mg/m² orally twice daily on days 1-14 of each 21-day cycle, for 6 cycles.
DRUGConsolidation treatment (Without ICIs)
CAPOX chemotherapy will consist of oxaliplatin 130 mg/m² intravenously on day 1 plus capecitabine 1000 mg/m² orally twice daily on days 1-14 of each 21-day cycle, for 6 cycles.
Sponsors
Shandong Cancer Hospital and Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Patients aged 18-75 years with histologically confirmed pMMR/MSS rectal adenocarcinoma are eligible if they have MRI-defined clinical stage II or III disease according to AJCC 8th edition, tumor located within 12 cm from the anal verge, and at least one high-risk feature, including cT4b, cN2, EMVI positivity, MRF positivity, lateral lymph node positivity, tumor deposits, or tumor located ≤5 cm from the anal verge. Patients must have no distant metastasis, ECOG performance status 0-1, life expectancy greater than 6 months, and adequate hematologic, hepatic, and renal function
Exclusion criteria
* active or prior autoimmune disease requiring systemic treatment, use of immunosuppressive therapy or systemic corticosteroids at immunosuppressive doses, severe hypersensitivity to monoclonal antibodies, uncontrolled cardiac disease, significant coagulopathy or bleeding tendency, active infection, interstitial lung disease or severe pulmonary dysfunction, HIV infection or active hepatitis, prior or concurrent malignancy except specified cured cancers, recent investigational drug use, planned use of other systemic antitumor therapy during the study, pregnancy or breastfeeding, and any other condition judged by the investigator to make participation unsuitable.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete Response (CR) Rate | From randomization to completion of definitive response assessment, including surgical pathological assessment after total neoadjuvant therapy or confirmation of sustained clinical complete response after at least 12 months of Watch-and-Wait follow-up | Complete response rate is defined as the proportion of patients who achieve either pathologic complete response (pCR) after surgery or sustained clinical complete response (cCR) for more than 1 year during Watch-and-Wait follow-up. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 3-Year Relapse-Free Survival (RFS) | From randomization to the first documented disease relapse/recurrence, death from any cause, or 3 years after randomization, whichever occurs first. | Relapse-free survival is defined as the time from randomization to the first evidence of disease relapse or recurrence. Patients without relapse/recurrence or death will be censored at the date of last disease assessment. |
| 3-Year Overall Survival (OS) | From randomization to death from any cause or 3 years after randomization, whichever occurs first. | Overall survival is defined as the time from randomization to death from any cause. Patients who are alive at the time of analysis will be censored at the date of last known survival follow-up. |
| Sphincter Preservation Rate | From randomization to completion of definitive surgery, or to at least 12 months after initiation of Watch-and-Wait follow-up for patients who do not undergo surgery; approximately up to 18-24 months after randomization. | Sphincter preservation rate is defined as the proportion of patients who successfully preserve anal sphincter structure and function and avoid permanent colostomy. |
| Incidence of Grade 3-4 Acute Adverse Events | From the start of study treatment to 30 days after completion of neoadjuvant treatment. | Acute adverse events will be graded and recorded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0. The incidence of grade 3-4 acute adverse events will be summarized by treatment arm. |
Countries
China
Contacts
CONTACTJinbo Yue Doctor
PRINCIPAL_INVESTIGATORJinbo Yue, Doctor
Study Principal Investigator
Outcome results
None listed