This is a prospective, single-arm, biomarker-stratified, multicenter phase 2 clinical trial. All enrolled patients first receive short-course radiotherapy (SCRT), followed by measurement of serum β-hydroxybutyrate (β-HB) levels to calculate the post-radiotherapy elevation rate. Patients are stratified into an β-HB-positive stratum (elevation significantly) and an β-HB-negative stratum (no elevation), then randomized 1:1 within each stratum to receive either perioperative chemotherapy plus PD-1 inhibitor or perioperative chemotherapy alone.
The primary endpoint is the complete response (CR) rate, defined as the composite of pathological complete response (pCR) and clinical complete response (cCR). The study aims to evaluate the efficacy and safety of adding PD-1 inhibitor to perioperative chemotherapy in LARC, and to validate post-radiotherapy β-HB elevation as a predictive biomarker for immunotherapy benefit.
Patients or their family members agree to participate in the study and sign the informed consent form;
Age 18-75 years, male or female;
Histologically confirmed Locally Advanced rectal adenocarcinoma;
inferior margin ≤ 10 cm from the anal verge;
Patients with non-pMMR LARC；
Subjects who have previously received any form of immunotherapy, including but not limited to immune checkpoint inhibitors, immune checkpoint agonists, immune cell therapy, or any other treatment targeting tumor immunomodulatory mechanisms;
Presence of any concurrent disease, condition (including laboratory abnormality), history of substance abuse, or current evidence thereof, which, in the judgment of the Investigator, may compromise subject safety, interfere with the process of obtaining informed consent, affect subject compliance, or confound the safety assessment of the investigational product(s).
Parallel
Short-course radiotherapy
RadiationEligible subjects will receive short-course radiotherapy (SCRT). One week after the end of treatment, subjects continued to receive neoadjuvant chemotherapy.
Capecitabine
Drug1000mg/m2, bid, po, d1-14,q3w
Oxaliplatin
Drug130mg/m2, ivgtt, d1,q3w
TME surgery
Procedure/SurgeryThe surgery was performed 1 week after the end of neoadjuvant therapy.
PD -1/PD-L1 monoclonal antibody
Drug200 mg via intravenous infusion every 3 weeks (q3w) for 6 cycles, initiated 1 week after radiotherapy completion.
Watch & Wait strategy
Other interventionThe Watch \& Wait (W\&W) strategy is an organ-preserving clinical management approach for patients with locally advanced rectal cancer who achieve a clinical complete response (cCR) after neoadjuvant therapy. In this strategy, definitive surgical resection (total mesorectal excision, TME) is withheld, and patients are instead managed with a standardized, intensive surveillance regimen to monitor for disease regrowth.
complete response (CR) rate
Defined as pathological complete response (pCR) + Clinical complete response (cCR)
3-year disease-Free Survival
The time from the first day of disease free (operation date) to local or distant recurrence, or the death event caused by any reason, whichever occurs first
Overall Survival
The time from the date of randomization to the death caused by any cause
Adverse events (AEs) were graded according to the NCI CTCAE version 5·0
Adverse events and surgical safety
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Tao Zhang
Lead sponsor
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Sponsor institution
This trial is not recruiting at the moment. You can still explore other options:
