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

Phase 2

Active, not recruiting

• Conditions: Locally Advanced Rectal Cancer
• Interventions: Drug: capecitabine; Drug: tislelizumab; Drug: thymalfasin; Radiation: long-term radiotherapy

• Registration Number: NCT06056804
• Lead Sponsor: Beijing Friendship Hospital

Brief Summary

This is an open, prospective, multi-center, single-arm phase II clinical study assessing the efficacy and safety of neoadjuvant chemoradiotherapy combined with PD-1 inhibitor and thymalfasin in patients with pMMR/MSS locally advanced middle and low rectal cancer.

Detailed Description

This study is an open, prospective, multi-center, single-arm phase II clinical study. In this study, patients with pMMR/MSS locally advanced middle and low rectal cancer were selected as the subjects and treated with neoadjuvant treatment protocol of long-course concurrent chemoradiotherapy combined with PD-1 monoclonal antibody and thymalfasin. The primary endpoint of the study was complete response (CR) rate. The secondary end points included treatment-related adverse events (TRAEs) rate, 30-day incidence of postoperative complications, objective response rate (ORR), 3-year disease-free survival (DFS) rate, Neoadjuvant rectal cancer (NAR) score, R0 resection rate, and anal preservation rate.

Study Timeline

• Study First Submitted: 2023-09-21
• Study First Submitted QC: 2023-09-21
• Study First Posted: 2023-09-28
• Study Start: 2024-01-03
• Status Verified: 2024-08
• Primary Completion: 2024-12-01
• Last Update Submitted: 2025-03-27
• Last Update Posted: 2025-04-02
• Study Completion: 2027-07-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

1. Patients who were fully informed of the study and voluntarily signed the informed consent form;
2. Patients with rectal cancers must satisfied all the following conditions:

1. Stage II/III LARC (cT3-4aN0M0 and cT1-4aN1-2M0); 2) Tumor distal located ≤ 10 cm from anal verge (MRI diagnosed); 3) pMMR or MSS confirmed by immunohistochemistry or genetic test. 3.Patients regardless of gender with aged ≥18 years and ECOG score of 0 or 1; 4. Physical and viscera function of patients can withstand major abdominal surgery; 5.Patients are willing and able to follow the study protocol during the study 6.Patients give consent to the use of pathological specimens for study 7.Within 28 days prior to enrolment, we must confirm a negative serological pregnancy test for child-bearing age women and they agree to use effective contraception for the duration of drug use and for 60 days after the last dose.

Exclusion Criteria

1. Patients have a present or previous active malignancy except the diagnosis of rectal cancer this time;
2. Patients underwent major surgery within 4 weeks prior to study treatment;
3. Patients have any condition affects the absorption of capecitabine through gastrointestinal tract;
4. Patients have severe uncontrolled recurrent infections, or other severe uncontrolled concomitant diseases;
5. Patients who are allergic to any of the ingredients under study;
6. Patients with severe concomitant diseases with estimated survival ≤ 5 years;
7. Patients with present or previous moderate or severe liver and kidney damage presently or previously;
8. Patients have received other study medications or any immunotherapy currently or in the past;
9. Patients preparing for or previously received organ or bone marrow transplant;
10. Patients who received immunosuppressive or systemic hormone therapy for immunosuppressive purposes within 1 month prior to the initiation of study therapy;
11. Patients with congenital or acquired immune deficiency (such as HIV infection);
12. If patients with a history of uncontrolled epilepsy, central nervous system disease or mental disorder, the investigator will determine whether the clinical severity prevents the signing of informed consent or affects the patient's oral medication compliance;
13. Patients with other factors that may affect the study results or cause the study to be terminated midway, such as alcoholism, drug abuse, other serious diseases (including mental illness) requiring combined treatment and severe laboratory examination abnormalities.
14. Pregnant or lactating women

Criteria for Withdrawal:

1. The subject withdraws informed consent;
2. The subject requests to withdraw from the study, or loses follow-up;
3. The subject demonstrates poor compliance and is unable to participate in the treatment and visits as required by the study protocol;
4. The subject experiences intolerable adverse events, and the investigator determines that continuing the study may be detrimental to the subject;
5. Other reasons, where the investigator determines it is not suitable for the subject to continue in the study.

Criteria for Study Termination:

1. There are major errors in the study protocol;
2. The study involves significant risks and is terminated following review by the ethics committee;
3. Termination requested by the sponsor or regulatory authorities.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
cCRT+tislelizumab+thymalfasin	long-term radiotherapy	A total of 20 pMMR/MSS locally advanced middle and low rectal cancer patients will receive long-course concurrent chemoradiotherapy combined with 3 cycles of tislelizumab and 11 weeks of thymalfasin therapy.
cCRT+tislelizumab+thymalfasin	capecitabine	A total of 20 pMMR/MSS locally advanced middle and low rectal cancer patients will receive long-course concurrent chemoradiotherapy combined with 3 cycles of tislelizumab and 11 weeks of thymalfasin therapy.
cCRT+tislelizumab+thymalfasin	tislelizumab	A total of 20 pMMR/MSS locally advanced middle and low rectal cancer patients will receive long-course concurrent chemoradiotherapy combined with 3 cycles of tislelizumab and 11 weeks of thymalfasin therapy.
cCRT+tislelizumab+thymalfasin	thymalfasin	A total of 20 pMMR/MSS locally advanced middle and low rectal cancer patients will receive long-course concurrent chemoradiotherapy combined with 3 cycles of tislelizumab and 11 weeks of thymalfasin therapy.

Primary Outcome Measures

Name	Time	Method
CR rate	from preoperative to 10 days postoperative	complete response rate, If patients achieved cCR after neoadjuvant therapy or were confirmed pCR after TME, they were considered as complete response (CR). pCR was defined as no residual tumor cells on the histologic examination of surgical specimens according to AJCC 8th edition. cCR was defined according to the Memorial Sloan Kettering Cancer Center (MSKCC) standard.

Secondary Outcome Measures

Name	Time	Method
30-day incidence of postoperative complications	within 30 days after surgery	incidence of surgical complications within 30 days after surgery
NAR score	within 10 days after surgery	neoadjuvant rectal score
TRAE	from commencing of treatment to the 30th day after surgery	incidence of treatment-related adverse event
ORR	before surgery	objective response rate; The ORR rate is the result of complete response (CR) rate plus partial response (PR) rate.
3-y DFS rate	3 years	3-year disease free survival rate
R0 resection rate	within 10 days after surgery	rate of R0 resection
anal preservation rate	instantly after surgery	proportion of patients with preserved anal sphincter

Trial Locations

Locations (2)

Peking Union Medical College Hospital; 🇨🇳 Beijing, China

Beijing Friendship Hospital,Capital Medical University; 🇨🇳 Beijing, China