Sintilimab Combined With LCCRT Followed by Capeox Chemotherapy in pMMR/MSS/MSI-L Locally Advanced Rectal Cancer

Sintilimab Combined With Long-Course Concurrent Chemoradiotherapy Followed by Capeox Consolidation Chemotherapy vs. Long-Course Concurrent Chemoradiotherapy Followed by Capeox Consolidation Chemotherapy for Total Neoadjuvant Therapy in Patients With Mismatch Repair-Proficient (pMMR) or Microsatellite Stable/Low Microsatellite Instability (MSS/MSI-L) Locally Advanced Rectal Cancer: A Multicenter, Randomized, Double-Blind, Controlled Phase III Study

This is a randomized, double-blind, controlled, Phase III clinical study to evaluate the efficacy and safety of sintilimab combined with long-course concurrent chemoradiotherapy followed by Capeox consolidation chemotherapy, which is planned to enroll 500 subjects with locally advanced rectal cancer.

Study Overview

• Status: Not yet recruiting
• Conditions: Locally Advanced Rectal Cancer
• Intervention / Treatment: Drug: Oxaliplatin; Drug: Placebo; Radiation: radiotherapy; Drug: Capecitabine; Procedure: Radical resection of rectal cancer; Drug: Sintilimab

• Study Type: Interventional
• Enrollment (Estimated): 500
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Yanxi Pu; Phone Number: +86-18523197816; Email: yanxi.pu@innoventbio.com

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Sun Yat sen University Cancer Center
      • Contact: Ruihua Xu; Phone Number: +86-20-87343468; Email: xurh2@sysucc.org.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

1. Has signed the written Informed Consent Form and is capable of complying with the visit schedules and relevant procedures specified in the protocol.
2. Histopathologically confirmed locally advanced rectal adenocarcinoma, with clinical stage cT3-4NanyM0 or cT1-2N1-2M0 as defined by the AJCC 8th edition, and assessed as amenable to R0 resection after neoadjuvant therapy. MRI demonstrates that the lower edge of the tumor is within 10 cm from the anal verge.
3. Tumor pathological tissue testing confirms pMMR, i.e., immunohistochemical staining shows positive expression of all four proteins MLH1, MSH2, MSH6, and PMS2, or tumor tissue-based genetic testing indicates MSI-L or MSS.
4. No signs of intestinal obstruction; or intestinal obstruction that has been relieved after proximal colostomy.
5. No prior rectal surgery; no prior systemic anti-cancer therapy, or other investigational drug therapy.
6. Age ≥18 years, both sexes eligible.
7. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.
8. Expected survival of ≥2 years.
9. Adequate bone marrow and organ function. Exclusion Criteria

1. Currently participating in another interventional clinical study, except for observational (non-interventional) clinical studies or those in the survival follow-up phase of an interventional study.

2. Plans to receive other anti-tumor therapy during the treatment period of this study.

3. Receipt of any live vaccine within 4 weeks before the first dose of study drug, or plans to receive any live vaccine during the study period.

4. Presence of toxicity from prior therapy that has not recovered to Grade 0 or 1 per NCI CTCAE V6.0 before the first dose of study drug (excluding alopecia, fatigue, pigmentation, and other conditions judged by the investigator to pose no safety risk).

5. Major surgery 6. Receipt of immunosuppressive therapy within 4 weeks before the first dose of study drug, excluding topical corticosteroids administered intranasally, by inhalation, or by other local routes, or physiological doses of systemic corticosteroids , or corticosteroids used to prevent contrast agent allergy.

7. Recurrent rectal cancer; multiple primary colorectal cancers. 8. History of pelvic or abdominal radiotherapy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo combined with long-course concurrent chemoradiotherapy followed by Capeox consolidation chemotherapy	Drug: Oxaliplatin; 130 mg/m²，IV，Q3W; Drug: Placebo; 20 ml D1 IV Q3W; Radiation: radiotherapy; PTV1 50 Gy/25 times, PTV2 45 Gy/25 times, 5 days a week, for a total of 5 weeks (D1-D35); Drug: Capecitabine; 825 mg/m ² PO BID ,Days 1-5 QW；1000mg/m ² PO BID ,Days 1-14 Q3W； Procedure: Radical resection of rectal cancer; Radical resection of rectal cancer
Experimental: Sintilimab; sintilimab combined with long-course concurrent chemoradiotherapy followed by Capeox consolidation chemotherapy	Drug: Oxaliplatin; 130 mg/m²，IV，Q3W; Radiation: radiotherapy; PTV1 50 Gy/25 times, PTV2 45 Gy/25 times, 5 days a week, for a total of 5 weeks (D1-D35); Drug: Capecitabine; 825 mg/m ² PO BID ,Days 1-5 QW；1000mg/m ² PO BID ,Days 1-14 Q3W； Procedure: Radical resection of rectal cancer; Radical resection of rectal cancer; Drug: Sintilimab; 200 mg D1 IV Q3W

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
EFS	EFS refers to the time from randomization to the first occurrence of any of the following events: disease progression precluding surgical treatment, local or distant recurrence, death from any cause, etc.	throutg treatment completion an average of 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OS	OS is defined as the time from the date of randomization until the date of death from any cause.	throutg treatment completion an average of 5 years
CCR	CCR defined as the proportion of participants achieving pathological complete response (pCR) or clinical complete response (cCR)	up to 5 years after enrollment
R0 resection rate	R0 resection rate: Descriptive summary of R0 resection rate	up to 5 years after enrollment
EFS3	EFS3 defined as the proportion of participants who remain free from any of the following events for 3 years after randomization: disease progression precluding surgery, local or distant recurrence, or death from any cause	3yaers
TRG	Pathological assessment of tumor regression grading (TRG) after neoadjuvant therapy	up to 5 years after enrollment
neoadjuvant therapy completion rate	Neoadjuvant therapy completion rate: Descriptive summary of Neoadjuvant therapy completion rate	up to 5 years after enrollment
OPR	The definition of organ preservation is: no radical total mesorectal excision (TME) performed, and no local regrowth, unless such regrowth can be salvaged by local excision achieving a limited, radical (R0) resection, with no permanent stoma (including a protective stoma that has never been reversed, or a stoma resulting from adverse events and/or poor functional outcome, or a permanent stoma).	up to 5 years after enrollment

Collaborators and Investigators

• Sponsor: Innovent Biologics (Suzhou) Co. Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): November 25, 2026
• Primary Completion (Estimated): March 25, 2030
• Study Completion (Estimated): November 24, 2031

Study Registration Dates

• First Submitted: October 19, 2026
• First Submitted That Met QC Criteria: October 30, 2026
• First Posted (Actual): November 4, 2026

Study Record Updates

• Last Update Posted (Actual): November 4, 2026
• Last Update Submitted That Met QC Criteria: October 30, 2026
• Last Verified: October 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Therapeutics; Nucleic Acids, Nucleotides, and Nucleosides; Coordination Complexes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Nucleosides; Uracil; Pyrimidinones; Deoxyribonucleosides; Fluorouracil; Capecitabine; Oxaliplatin; Radiotherapy; sintilimab
• Other Study ID Numbers: CIBI308H301

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No