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AzTrials

Locally Advanced Rectal Cancer (LARC)Phase 2NCT06933251

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

A Phase 2 study testing Neoadjuvant Chemoradiotherapy Combined with PD-1 inhibitor Immunotherapy and PCSK9 Inhibitor Therapy in people with Locally Advanced Rectal Cancer (LARC), run by Guangdong Provincial People's Hospital at 2 sites in China.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Locally Advanced Rectal Cancer (LARC)
What is being tested?
Neoadjuvant Chemoradiotherapy Combined with PD-1 inhibitor Immunotherapy and PCSK9 Inhibitor Therapy
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
2 sitesChina
Study dates
20 Apr 2025to 28 Feb 2030
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.;
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  • 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;
  • History of hypocholesterolemia (total cholesterol [TC] <3.6 mmol/L or <140 mg/dL, low-density lipoprotein cholesterol [LDL-C] <1.8 mmol/L or <70 mg/dL, high-density lipoprotein cholesterol [HDL-C] <1.0 mmol/L [male] or <1.3 mmol/L [female]), hypolipidemia (triglycerides [TG] <0.5 mmol/L or <45 mg/dL), or a family history of these conditions.

Trial locations and contacts

2 sites in 1 country.

China2 sites

  • Guangdong Provincial People's Hospital

    Guangzhou, Guangdong, 510080

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

    Guangzhou, Guangdong

Other trials in China

About this study

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

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.

Read the 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.

Being tested
Neoadjuvant Chemoradiotherapy Combined with PD-1 inhibitor Immunotherapy and PCSK9 Inhibitor Therapy
Keywords
neoadjuvant chemoradiotherapy, PD-1 inhibitor, PCSK9 inhibitor, pMMR/MSS

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Neoadjuvant Chemoradiotherapy Combined with PD-1 inhibitor Immunotherapy and PCSK9 Inhibitor TherapyDrug

    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.

Study groups in NCT06933251
Study groupRoleWhat they receive
Neoadjuvant Chemoradiotherapy Combined with Immunotherapy and PCSK9 inhibitor TreatmentExperimentalBuilding on short-term radiotherapy combined with chemotherapy, the treatment integrates PD-1 inhibitor immunotherapy and PCSK9 inhibitor therapy.
Receives: Drug: Neoadjuvant Chemoradiotherapy Combined with PD-1 inhibitor Immunotherapy and PCSK9 Inhibitor Therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. CR

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

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

  2. AE rate

    Adverse event rate

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

Secondary outcomes (5)

  1. DFS

    Disease-free survival

    Measured: 5 years

  2. OS

    Overall survival time

    Measured: 5 years

  3. ORR

    objective response rate

    Measured: within 2 weeks after surgery

  4. TRG

    Tumor regression grade

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

  5. OPR

    organ preservation rate

    Measured: immediately after surgery

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Apr 2025
  2. Study start20 Apr 2025
  3. Primary completion28 Feb 2030 (estimated)
  4. Study completion28 Feb 2030 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
30 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06933251
Sponsor's protocol ID
PIONEER-01
Status last verified
Jul 2026
First submitted
6 Mar 2025
Last updated
8 Jul 2026
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 33177715

  • 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.

    PubMed 33606190

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Neoadjuvant Chemoradiotherapy Combined with PD-1 inhibitor Immunotherapy and PCSK9 Inhibitor Therapy in people with Locally Advanced Rectal Cancer (LARC), run by Guangdong Provincial People's Hospital at 2 sites in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 8 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

CR (time frame: pCR :within 2 weeks after surgery; cCR :2 weeks after radiotherapy ends). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06933251, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jul 2026.

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