Yang et al. Anti-PD-1/CTLA-4 Dual Immunotherapy for LARC
Trial statusNot yet recruiting
Trial phasePhase 2, Phase 3
Trial typeInterventional
Biological sexAll
Age18-80
SponsorBeijing Friendship Hospital
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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;
Disqualifiers
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;
Trial design
Design model
Parallel
Treatments tested in this trial
Short-course radiotherapy
RadiationArm A receive short-course radiotherapy
Long-course radiotherapy
RadiationArm B and C will receive long-course radiotherapy
Immunotherapy
DrugAnti-PD-1/CTLA-4 Dual Immunotherapy (paromlimab and Tuvonralimab)
Treatment groups
342 Participants
are divided into 3 treatment groupsGroup A: Arm AExperimental treatment 2 interventions
Group B: Arm BExperimental treatment 2 interventions
Group C: Arm CNo intervention 0 interventions
Trial outcomes
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.
Time frame
3 yearSecondary outcomes
1
Proportion of patients adopting the "wait-and-watch" strategy
The "wait-and-watch" (or "watch-and-wait") proportion refers to the percentage of patients who, after achieving a clinical complete response (cCR) following neoadjuvant therapy, opt for active surveillance with organ preservation rather than proceeding to radical surgery. This metric reflects real-world adoption of the watch-and-wait strategy and is influenced by multiple factors, including physician recommendations, institutional protocols, patient preferences, and local healthcare infrastructure. A higher proportion indicates greater clinical acceptance of non-operative management as a viable alternative for selected responders.
Time frame
3 years2
disease-free survival
the length of time after primary treatment during which a patient remains alive with no signs or symptoms of cancer recurrence.
Time frame
3 years3
overall survival
the length of time from diagnosis or initiation of treatment until death from any cause
Time frame
3 years4
near-pathological complete response
Near-pathological complete response (near-pCR) is defined as the presence of only minimal residual tumor (typically classified as ypT1 or isolated scattered residual tumor cells) in the resected specimen following neoadjuvant therapy, with all regional lymph nodes negative (ypN0). It represents a near-complete tumor regression that falls just short of the strict pCR definition (ypT0N0) but is nonetheless associated with significantly favorable oncological outcomes, approaching those of true pCR. Near-pCR serves as an intermediate endpoint between complete and partial pathological response and has been increasingly recognized as a clinically meaningful predictor of long-term survival benefit.
Time frame
3 yearsLocations
Sponsors and contacts
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Beijing Friendship Hospital
Lead sponsor
Peking University Cancer Hospital & Institute
Collaborator
Peking Union Medical College
Collaborator
Source ClinicalTrials.gov
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