This is a randomized, controlled clinical trial based on prior exploratory findings, designed to evaluate the efficacy and safety of neoadjuvant chemoradiotherapy combined with tafolecimab(an anti-PCSK9 inhibitor) and sintilimab (an anti-PD-1 inhibitor) versus neoadjuvant chemoradiotherapy combined with sintilimab alone in patients with pMMR/MSS locally advanced rectal cancer. The primary endpoint is the complete response (CR) rate, including the pathological complete response (pCR) rate in patients who undergo surgery after neoadjuvant therapy, and the clinical complete response (cCR) rate in patients managed with a watch-and-wait strategy. Secondary endpoints include major pathological response (MPR) rate, objective response rate (ORR), downstaging rate, R0 resection rate, tumor regression grade, sphincter preservation rate, disease-free survival (DFS), overall survival (OS), and safety.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
148
Total dose: 25 Gy, to be completed in 5 sessions (once a day for 5 days). After the short-course radiotherapy, a 1-week rest is required before moving on to the next stage of treatment.
One week after short-course radiotherapy, 6 cycles of CAPOX chemotherapy combined with PD-1 inhibitor immunotherapy were administered. Each cycle lasted for 3 weeks, for a total of 6 cycles. (One cycle is defined as: Oxaliplatin, 130 mg/m², intravenous infusion, on day 1. Capecitabine, 1000 mg/m², orally, twice a day (morning and evening), from day 1 to day 14.)
For patients with a body weight of less than 60 kg, the dose is 3 mg/kg, administered by intravenous infusion on the first day; for patients with a body weight of 60 kg or more, the dose is 200 mg, also administered by intravenous infusion on the first day.
The entire course of treatment with PCSK9 inhibitor (Tafolecimab) was administered, with 450 mg of Tafolecimab administered subcutaneously. (The treatment involved neoadjuvant radiotherapy and chemotherapy combined with immunotherapy and Tafolecimab. The treatment was carried out from the time the patient began receiving short-course radiotherapy. Each cycle consisted of 4 weeks, with injection on the first day of each cycle, for a total of 6 times.)
Guangdong Provincial People's Hospital
Guangzhou, Guangdong, China
Complete Response (CR) Rate
Defined as the Proportion of Participants Achieving Pathological Complete Response (pCR) After Surgery or Clinical Complete Response (cCR) Under Watch-and-Wait Strategy Following Neoadjuvant Therapy
Time frame: Within 4 weeks after completion of neoadjuvant therapy for cCR and within 2 weeks after the time of surgery for pCR
Number of Participants with Treatment-Related Adverse Events as Assessed by CTCAE v5.0
Time frame: From the first dose of neoadjuvant treatment
Major Pathological Response (MPR) Rate
Time frame: within 2 weeks after the time of surgery
Objective Response Rate (ORR)
Time frame: Within 4 weeks after completion of neoadjuvant therapy or within 2 weeks after surgery;
Downstaging Rate
Time frame: Within 4 weeks after completion of neoadjuvant therapy or within 2 weeks after surgery;
Tumor Regression Grade (TRG)
Time frame: Within 2 weeks after surgery;
R0 Resection Rate
Time frame: Within 2 weeks after surgery;
Disease-Free Survival (DFS)
Time frame: approximately 5 years after completion of neoadjuvant chemotherapy
Overall Survival (OS)
Time frame: approximately 5 years after completion of neoadjuvant chemotherapy
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