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Low-Dose Radiotherapy to Sensitize Pucotenlimab Plus CAPEOX for pMMR Locally Advanced Rectal Cancer
Sponsor: Sun Yat-sen University
Summary
This is a prospective, open-label, randomized, parallel-group phase II trial evaluating the efficacy and safety of a low-dose radiotherapy sensitization strategy combined with a PD-1 antibody (pucotenlimab) and CAPEOX as neoadjuvant therapy in patients with pMMR/MSS locally advanced rectal adenocarcinoma. Participants will be randomized 1:1 to receive either 2 Gy or 5 Gy low-dose radiotherapy. Low-dose radiotherapy is delivered as a single fraction of 2 Gy (Arm A) or 5 Gy (Arm B). On the day after radiotherapy, participants will start pucotenlimab 200 mg IV Q3W (administered on Day 2 of each 21-day cycle) plus CAPEOX chemotherapy. Early response will be assessed after 2 cycles using endoscopy and pelvic MRI to guide subsequent treatment: participants with partial response may discontinue radiotherapy and continue neoadjuvant systemic therapy; participants with stable disease may switch to standard chemoradiotherapy; participants with progressive disease will receive multidisciplinary-team-guided salvage therapy. After 4 cycles, participants with clinical complete response may adopt a watch-and-wait strategy; otherwise, they will undergo radical surgery 2-4 weeks after completion of neoadjuvant therapy. Long-term follow-up will include recurrence and survival outcomes and quality of life.
Official title: A Randomized, Two-Arm, Open-Label Phase II Trial of Low-Dose Radiotherapy Sensitization Combined With Pucotenlimab and CAPEOX as Neoadjuvant Therapy for pMMR/MSS Locally Advanced Rectal Adenocarcinoma
Key Details
Gender
All
Age Range
18 Years - 75 Years
Study Type
INTERVENTIONAL
Enrollment
50
Start Date
2026-03-15
Completion Date
2032-09-01
Last Updated
2026-03-04
Healthy Volunteers
No
Conditions
Interventions
Low-dose radiotherapy
Low-dose radiotherapy delivered by linear accelerator to the primary rectal tumor and regional lymphatic drainage areas using IMRT or 3D-CRT techniques. Participants receive either 2 Gy or 5 Gy according to randomized assignment, administered prior to initiation of systemic neoadjuvant therapy.
Pucotenlimab
Pucotenlimab is a programmed cell death protein 1 (PD-1) monoclonal antibody. It is administered at a fixed dose of 200 mg by intravenous infusion on Day 2 of each 21-day cycle, every 3 weeks (Q3W), during the neoadjuvant treatment phase.
CAPEOX/XELOX
CAPEOX chemotherapy consists of oxaliplatin 130 mg/m² administered intravenously on Day 1 and capecitabine 1000-1250 mg/m² administered orally twice daily on Days 1-14 of each 21-day cycle during neoadjuvant therapy.
Locations (1)
Dept. of Colorectal Surgery, Sun Yat-sen University Cancer Center. Yuexiu District, Dongfeng East Road 651
Guangzhou, Guanggong, China