NCT06933251

PCSK9 Inhibitor and PD-1 Inhibitor Combined With Neoadjuvant Chemoradiotherapy for pMMR/MSS Locally Advanced Rectal Cancer

Clinical Study of PCSK9 Inhibitor and PD-1 Inhibitor Combined With Neoadjuvant Chemoradiotherapy in the Treatment of pMMR/MSS Locally Advanced Rectal Cancer

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Sponsor: Guangdong Provincial People's Hospital · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

This is a single-center, open-label, single-arm clinical study aimed at conducting a preliminary evaluation of the efficacy and safety of combining PCSK9 inhibitors and PD-1 inhibitors (dual inhibitors) with neoadjuvant chemoradiotherapy in patients with pMMR/MSS locally advanced rectal cancer.

Detailed description

This study aims to evaluate the complete response (CR) rate of PCSK9 inhibitor and PD-1 inhibitor combination therapy (dual inhibitors) in conjunction with neoadjuvant chemoradiotherapy for patients with pMMR/MSS locally advanced rectal cancer. Specifically, the study will assess the pathological complete response (pCR) rate two weeks after neoadjuvant therapy, the clinical complete response (cCR) rate under the "watch-and-wait" strategy, objective response rate (ORR), R0 resection rate, tumor regression grade (TRG), and sphincter preservation rate. Additionally, the study will evaluate the 2-year disease-free survival (DFS) and overall survival (OS) following dual-inhibitor combined neoadjuvant chemoradiotherapy. The safety and tolerability of this combination therapy will also be comprehensively assessed based on NCI-CTCAE 4.03 criteria.

Conditions

• Locally Advanced Rectal Cancer (LARC)

Interventions

Type	Name	Description
DRUG	Neoadjuvant Chemoradiotherapy Combined with PD-1 inhibitor Immunotherapy and PCSK9 Inhibitor Therapy	1. Neoadjuvant Treatment 1.1 Short-Course Radiotherapy (SCRT) Total Dose: 25 Gy in 5 fractions over 5 days. Interval: 1-week rest before the next stage. 1.2 Chemotherapy and Immunotherapy Regimen: Start 1 week after SCRT with 6 cycles of CAPOX chemotherapy combined with PD-1 inhibitor immunotherapy (3 weeks per cycle). 1.3 PCSK9 Inhibitor Administration: Subcutaneous injection every 4 weeks during neoadjuvant therapy (6 cycles total). 2. Multidisciplinary Team (MDT) Discussion Timing: 2 weeks after completing neoadjuvant therapy. Approach: Patients achieving clinical complete response (cCR): "Watch-and-wait" strategy. Others: Surgery based on MDT evaluation.

Timeline

• Start date: 2025-01-20
• Primary completion: 2030-02-28
• Completion: 2030-02-28
• First posted: 2025-04-18
• Last updated: 2026-03-09

Locations

2 sites across 1 country: China