Anti-PCSK9 Antibody Tafolecimab and Anti-PD-1 Antibody Sintilimab Combined With Neoadjuvant Chemoradiotherapy for pMMR/ MSS Locally Advanced Rectal Cancer : A Prospective, Multicenter, Randomized, Open-Label, Parallel-Controlled Trial

Summary

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.

Conditions

• Local Advanced Rectal Cancer
• PD-1 Inhibitor
• PCSK9 Inhibitor
• RCT
• Radiotherapy
• Capecitabine
• Oxaliplatin

Interventions

RADIATION

Short-course radiotherapy

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.

DRUG

CAPOX (oxaliplatin/capecitabine)

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.)

DRUG

Sintilimab

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.

DRUG

Tafolecimab

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.)

Sponsors & Collaborators

• Beijing Friendship Hospital

  collaborator OTHER

• Cancer Institute and Hospital, Chinese Academy of Medical Sciences

  collaborator OTHER

• Fudan University

  collaborator OTHER

• Sixth Affiliated Hospital, Sun Yat-sen University

  collaborator OTHER

• Sun Yat-Sen University Cancer Center

  collaborator OTHER

• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

  collaborator OTHER

• Affiliated Hospital of Qinghai University

  collaborator OTHER

• Zhangzhou Hospital, Fujian Province

  collaborator UNKNOWN

• The First Affiliated Hospital of Xiamen University

  collaborator OTHER

• Ruijin Hospital

  collaborator OTHER

• The First Hospital of Jilin University

  collaborator OTHER

• Peking University Cancer Hospital & Institute

  collaborator OTHER

• Nanchang University Second Affiliated Hospital

  collaborator UNKNOWN

• The First Affiliated Hospital, Guangzhou University of Traditional Chinese Medicine

  collaborator OTHER

• Third Affiliated Hospital, Sun Yat-Sen University

  collaborator OTHER

• Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

  collaborator OTHER

• Meizhou People's Hospital

  collaborator OTHER

• Guangdong Provincial People's Hospital

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

75 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2027-01-01

Primary Completion

2030-01-01

Completion

2035-01-01

Countries

• China

Study Locations