Yang et al. Anti-PD-1/CTLA-4 Dual Immunotherapy for LARC

NCT07596290 | Not Yet Recruiting Phase 2 DMC

• 2 other identifiers: 2026-RCT-RADICAL Trial2026-1-2023
• Study Type: interventional
• Target: 342
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a prospective, multicenter, randomized controlled trial aimed at comparing different radiotherapy fractionation regimens combined with sequential dual immunotherapy versus traditional chemoradiotherapy in neoadjuvant treatment for locally advanced rectal cancer (LARC). A total of 342 pMMR/MSS LARC patients will be enrolled and randomly assigned in a 1:1:1 ratio to short-course radiotherapy (5×5Gy) followed by sequential dual immunotherapy (paromlimab + tuvonralimab + CAPEOX), long-course radiotherapy followed by sequential dual immunotherapy, or conventional long-course chemoradiotherapy. The primary endpoint is the complete response rate (pCR + cCR). Secondary endpoints include the proportion of patients adopting the "watch-and-wait" strategy, disease-free survival, overall survival, and safety. This study innovatively explores the synergistic mechanism of different radiotherapy fractionations with dual immunotherapy, optimizes the timing of immunotherapy initiation, and constructs a clinical-imaging-pathology multimodal efficacy prediction model, aiming to advance LARC treatment from empirical to precision therapy while achieving organ and function preservation.

Conditions

Locally Advanced Rectal Adenocarcinoma; Neoadjuvant Chemoradiation; Neoadjuvant Immunotherapy

Keywords

Locally advanced rectal cancer; Neoadjuvant chemoradiation; Anti-PD-1/CTLA-4 Dual Immunotherapy; Short-course radiotherapy; Long-course rediotherapy

Outcome Measures

Primary Outcomes (1)

• Complete response

  pCR is defined as the complete absence of viable tumor cells in the surgically resected specimen, including both the primary tumor bed and all regional lymph nodes, following neoadjuvant therapy. It corresponds to ypT0N0 in the TNM staging system and is confirmed by histopathological examination of the total mesorectal excision (TME) specimen. pCR is considered the gold standard for confirming complete tumor eradication. cCR is defined as the complete absence of detectable tumor on all available preoperative clinical assessments - including digital rectal examination, endoscopy, and pelvic MRI - following neoadjuvant therapy, without pathological confirmation. The most widely adopted criteria were proposed by Habr-Gama et al., requiring: (1) normal or whitish scarred mucosa without ulceration or mass on endoscopy; (2) no palpable induration or nodularity on DRE; and (3) no residual tumor signal or restricted diffusion on pelvic MRI. cCR is inherently an imperfect surrogate for pCR.

  3 year

Secondary Outcomes (7)

• Proportion of patients adopting the "wait-and-watch" strategy

  3 years

• disease-free survival

  3 years

• overall survival

  3 years

• near-pathological complete response

  3 years

• grade ≥3 neoadjuvant treatment-related adverse events

  3 years

Study Arms (3)

Arm A

EXPERIMENTAL

Short-course radiotherapy + sequential dual immunotherapy group

Radiation: Short-course radiotherapy; Drug: Immunotherapy

Arm B

EXPERIMENTAL

Long-course radiotherapy + sequential dual immunotherapy group

Radiation: Long-course radiotherapy; Drug: Immunotherapy

Arm C

NO INTERVENTION

Traditional long-course chemoradiotherapy group

Interventions

Short-course radiotherapy RADIATION

Arm A receive short-course radiotherapy

Arm A

Long-course radiotherapy RADIATION

Arm B and C will receive long-course radiotherapy

Arm B

Immunotherapy DRUG

Anti-PD-1/CTLA-4 Dual Immunotherapy (paromlimab and Tuvonralimab)

Arm A; Arm B

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age between 18 and 80 years; ECOG performance status 0-1;
• Histopathologically confirmed rectal adenocarcinoma via colonoscopy; pMMR or MSS phenotype;
• Rectal MRI stage II/III (excluding T4b); distal tumor margin ≤ 12 cm from the anal verge;
• Willingness to comply with study procedures; consent to use tissue and blood samples for medical research purposes;
• No prior history of radiotherapy, chemotherapy, or immunotherapy;
• No immune system diseases (e.g., systemic lupus erythematosus, rheumatoid arthritis, systemic vasculitis, scleroderma, pemphigus, dermatomyositis, mixed connective tissue disease, hyperthyroidism/hypothyroidism, ulcerative colitis, autoimmune hemolytic anemia, HIV infection, etc.);
• No severe cardiac, pulmonary, hepatic, or renal dysfunction; no jaundice or gastrointestinal obstruction;
• No concurrent acute infection;
• Baseline laboratory evaluations completed as required, with results obtained within 14 days before randomization, and laboratory values meeting the following criteria (per CTCAE 5.0):
• White blood cell count ≥ 2000/μL;
• Neutrophil count ≥ 1500/μL;
• Platelet count ≥ 100×10³/μL;
• Hemoglobin ≥ 9.0 g/dL;
• Serum creatinine ≤ 1.5×upper limit of normal (ULN) or creatinine clearance \> 50 mL/min (female: creatinine clearance = \[140 - age (years)\] × body weight (kg) × 0.85 / (72 × serum creatinine (mg/dL)); male: creatinine clearance = \[140 - age (years)\] × body weight (kg) × 1.00 / (72 × serum creatinine (mg/dL)));
• AST ≤ 3×ULN, ALT ≤ 3×ULN, total bilirubin ≤ 1.5×ULN;

You may not qualify if:

• Multiple primary cancers or concurrent other malignant tumors;
• Patients requiring emergency surgery due to intestinal obstruction, intestinal perforation, gastrointestinal bleeding, etc.;
• Factors affecting oral drug absorption (e.g., inability to swallow, nausea/vomiting, diarrhea, intestinal obstruction, etc.);
• Any uncontrolled, severe concomitant diseases;
• Hypersensitivity to any component of the study drugs;
• Expected survival \< 5 years for any reason;
• Planned or previous organ/bone marrow transplantation;
• Treatment with immunosuppressants or corticosteroids within 1 month before enrollment;
• Central nervous system disorders that may impair ability to provide informed consent or comply with study procedures, as determined by the investigator;
• Other conditions that may prevent completion of study treatment (e.g., alcoholism, drug addiction, etc.);
• Pregnant or breastfeeding women.

Sponsors & Collaborators

• Beijing Friendship Hospital: lead
• Peking University Cancer Hospital & Institute: collaborator
• Peking Union Medical College: collaborator

MeSH Terms

Interventions

Immunotherapy

Intervention Hierarchy (Ancestors)

Immunomodulation; Biological Therapy; Therapeutics

Central Study Contacts

Yang yinchi yinchi, Doctor

CONTACT

15810152032; yangyingchi2004@sina.com

Li Ganbin, Doctor

CONTACT

18801053803; ligb0808@163.com

Study Design

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

Model Details: All patients meeting the inclusion and exclusion criteria will be randomly assigned in a 1:1:1 ratio to the short-course radiotherapy + sequential dual immunotherapy group, long-course radiotherapy + sequential dual immunotherapy group, or traditional long-course chemoradiotherapy group.

Study Record Dates

• First Submitted: May 10, 2026
• First Posted: May 19, 2026
• Study Start: May 15, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2030
• Last Updated: May 22, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share