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

NCT06933251 | Active Not Recruiting Phase 2

• 1 other identifier: lron-Man 03
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Locally Advanced Rectal Cancer (LARC)

Keywords

neoadjuvant chemoradiotherapy; PD-1 inhibitor; PCSK9 inhibitor; pMMR/MSS

Outcome Measures

Primary Outcomes (2)

• CR

  complete response rate=(number of pathological complete responses + number of clinical complete responses)/total number of patients

  pCR :within 2 weeks after surgery; cCR :2 weeks after radiotherapy ends

• AE rate

  Adverse event rate

  During neoadjuvant chemoradiotherapy combined with immunotherapy, an average of 6 months

Secondary Outcomes (5)

• DFS

  5 years

• OS

  5 years

• ORR

  within 2 weeks after surgery

• TRG

  At the time of postoperative pathological assessment (within 1 week after surgery)

• OPR

  immediately after surgery

Study Arms (1)

Neoadjuvant Chemoradiotherapy Combined with Immunotherapy and PCSK9 inhibitor Treatment

EXPERIMENTAL

Building on short-term radiotherapy combined with chemotherapy, the treatment integrates PD-1 inhibitor immunotherapy and PCSK9 inhibitor therapy.

Drug: Neoadjuvant Chemoradiotherapy Combined with PD-1 inhibitor Immunotherapy and PCSK9 Inhibitor Therapy

Interventions

Neoadjuvant Chemoradiotherapy Combined with PD-1 inhibitor Immunotherapy and PCSK9 Inhibitor Therapy DRUG

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.

Neoadjuvant Chemoradiotherapy Combined with Immunotherapy and PCSK9 inhibitor Treatment

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age between 18 and 75 years, regardless of gender;
• Histologically confirmed pMMR/MSS rectal adenocarcinoma, with clinical staging of cT3/T4 or cN+, and tumor located ≤12 cm from the anal verge;
• No distant metastasis;
• ECOG performance status of 0-1;
• Baseline hematological and biochemical parameters meet the following criteria: neutrophils ≥1.5×10\^9/L, hemoglobin ≥90 g/L, platelets ≥100×10\^9/L, ALT/AST ≤2.5 ULN, creatinine ≤1 ULN;
• Good compliance and willingness to sign an informed consent form.

You may not qualify if:

• History of allergies to PCSK9 monoclonal antibody, PD-1 monoclonal antibody, capecitabine, or oxaliplatin;
• Preoperative pathological diagnosis of non-pMMR/MSS rectal adenocarcinoma;
• Use of other long-term lipid-lowering drugs leading to conditions such as hypolipidemia;
• Pregnant or breastfeeding women;
• History of other malignancies within the past 5 years;
• Previous history of anti-tumor treatments, including radiotherapy, chemotherapy, immune checkpoint inhibitors, T-cell related therapies, etc.;
• History of severe neurological or psychiatric disorders (e.g., schizophrenia, dementia, or epilepsy);
• Current severe cardiovascular disease (heart failure or arrhythmia), renal insufficiency, or liver dysfunction; Note: Whether the patient can tolerate the specific treatment or measures should be assessed by a cardiologist based on the patient's condition.
• Acute myocardial infarction or ischemic stroke within 6 months prior to enrollment;
• Presence of uncontrolled infections requiring systemic treatment;
• Active autoimmune diseases or immunodeficiencies, a history of organ transplantation, or systemic use of immunosuppressive agents;
• Known history of HIV infection (e.g., HIV 1-2 antibody positive), active syphilis, or active pulmonary tuberculosis;
• Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection during screening (e.g., HBsAg positive, HBV DNA positive, HCV RNA positive, or anti-HCV antibody positive);
• Known allergy to any component of the treatment;
• Investigator's judgment that other factors exist which may cause early termination of the trial, such as severe disease (including psychiatric disorders), alcohol abuse, drug use, or social or familial factors affecting patient safety or compliance;

Sponsors & Collaborators

• Guangdong Provincial People's Hospital: lead

Study Sites (2)

Guangdong Provincial People's Hospital

Guangzhou, Guangdong, 510080, China

Location

No. 106, Zhongshan 2nd Road, Yuexiu District, Guangzhou

Guangzhou, Guangdong, China

Location

Related Publications (2)

• Liu X, Bao X, Hu M, Chang H, Jiao M, Cheng J, Xie L, Huang Q, Li F, Li CY. Inhibition of PCSK9 potentiates immune checkpoint therapy for cancer. Nature. 2020 Dec;588(7839):693-698. doi: 10.1038/s41586-020-2911-7. Epub 2020 Nov 11.

  PMID: 33177715 RESULT

• Yuan J, Cai T, Zheng X, Ren Y, Qi J, Lu X, Chen H, Lin H, Chen Z, Liu M, He S, Chen Q, Feng S, Wu Y, Zhang Z, Ding Y, Yang W. Potentiating CD8+ T cell antitumor activity by inhibiting PCSK9 to promote LDLR-mediated TCR recycling and signaling. Protein Cell. 2021 Apr;12(4):240-260. doi: 10.1007/s13238-021-00821-2. Epub 2021 Feb 19.

  PMID: 33606190 RESULT

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 6, 2025
• First Posted: April 18, 2025
• Study Start: January 20, 2025
• Primary Completion (Estimated): February 28, 2030
• Study Completion (Estimated): February 28, 2030
• Last Updated: March 9, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)