Sintilimab Plus Gossypol Acetate in Advanced Colorectal Cancer

A Single-Arm, Open-Label, Exploratory Phase II Clinical Trial of Sintilimab Plus Gossypol Acetate in Patients With Advanced pMMR/MSS Colorectal Cancer After Failure of at Least Two Prior Lines of Therapy

This is a single-center, open-label, single-arm, exploratory phase II clinical trial designed to evaluate the preliminary efficacy and safety of sintilimab in combination with oral gossypol acetate in patients with advanced pMMR/MSS colorectal cancer after failure of at least two prior lines of standard therapy. Eligible participants will have histologically or cytologically confirmed advanced colorectal adenocarcinoma, measurable disease according to RECIST version 1.1, ECOG performance status of 0 or 1, and adequate organ function. Participants will receive oral gossypol acetate once daily, followed by sintilimab administered intravenously every 3 weeks after a gossypol acetate lead-in period. The primary outcome is objective response rate assessed by RECIST version 1.1. Secondary outcomes include disease control rate, progression-free survival, overall survival, duration of response, and safety.

Study Overview

• Status: Not yet recruiting
• Conditions: Advanced Colorectal Cancer
• Intervention / Treatment: Drug: Sintilimab; Drug: Gossypol Acetate

• Study Type: Interventional
• Enrollment (Estimated): 32
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ziwei Zhang; Phone Number: +86 18883886902; Email: 786327832@qq.com

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100044
      • Peking University People's Hospital
      • Contact: Peking University People's Hospital; Phone Number: +86 18883886902; Email: shenzhanlong@pkuph.edu.cn
      • Principal Investigator: Zhanlong Shen, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Written informed consent provided before any study-specific procedures.
2. Age 18 to 75 years, male or female.
3. Histologically or cytologically confirmed advanced colorectal adenocarcinoma.
4. Confirmed pMMR/MSS tumor status. Participants without documented MSI/MMR status must undergo MSI or MMR testing during screening.
5. Disease progression after at least two prior lines of standard therapy.
6. Availability of tumor tissue suitable for pathological evaluation and biomarker analysis.
7. ECOG performance status of 0 or 1 within 7 days before the first dose of study treatment.
8. At least one measurable lesion according to RECIST version 1.1.
9. Adequate hematologic, hepatic, renal, coagulation, and organ function as defined in the protocol.
10. Female participants of childbearing potential must have a negative pregnancy test before initiation of study treatment and agree to use effective contraception during the study and for the protocol-specified period after the last dose.

Exclusion Criteria:

1. Histology of small cell carcinoma, squamous cell carcinoma, or mixed carcinoma.
2. dMMR/MSI-H tumor status.
3. Complete bowel obstruction or clinical conditions likely to progress to bowel obstruction.
4. Suspected bowel perforation based on clinical symptoms or imaging.
5. History of malignancy other than colorectal cancer within 3 years before screening, except malignancies with negligible risk of metastasis or death and treated with expected curative outcome.
6. Active autoimmune disease, history of autoimmune disease, or immunodeficiency requiring systemic treatment, except protocol-allowed conditions.
7. Significant cardiovascular disease within 3 months before initiation of study treatment, including New York Heart Association class II or higher heart disease, myocardial infarction, cerebrovascular accident, unstable arrhythmia, or unstable angina.
8. History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT.
9. Severe chronic or active infection within 4 weeks before initiation of study treatment.
10. Active tuberculosis infection or inadequately treated prior active tuberculosis.
11. Active hepatitis B or hepatitis C infection as defined by protocol criteria.
12. Uncontrolled tumor-related pain, uncontrolled pleural effusion, pericardial effusion, or ascites requiring frequent drainage.
13. History of leptomeningeal disease.
14. Prior treatment with CD137 agonists, T-cell co-stimulatory agents, or immune checkpoint inhibitors, including anti-CTLA-4, anti-PD-1, anti-PD-L1, or anti-TIGIT antibodies.
15. Treatment with systemic immunostimulatory agents within 4 weeks or 5 half-lives before initiation of study treatment, whichever is longer.
16. Treatment with systemic immunosuppressive medications within 2 weeks before initiation of study treatment, except protocol-allowed medications.
17. Prior allogeneic stem cell transplantation or solid organ transplantation.
18. Receipt of a live attenuated vaccine within 4 weeks before initiation of study treatment or expected need for such vaccination during the study or within 5 months after the last dose of sintilimab.
19. Major surgery or severe traumatic injury within 28 days before initiation of study treatment, abdominal surgery or abdominal intervention within 60 days before initiation of study treatment, or expected need for major surgery during the study.
20. Receipt of any other investigational drug within 28 days before initiation of study treatment.
21. Known contraindication, hypersensitivity, or severe allergic reaction to any study drug or its excipients.
22. Pregnancy, breastfeeding, or intention to become pregnant during the study or within 5 months after the last dose of sintilimab.
23. Any other disease, laboratory abnormality, social condition, or medical condition that, in the investigator's judgment, may compromise participant safety, interfere with study compliance, or affect interpretation of study results.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Experimental: Sintilimab Plus Gossypol Acetate; Participants will receive oral gossypol acetate and intravenous sintilimab according to the study protocol.

Drug: Sintilimab; Sintilimab 200 mg will be administered intravenously every 3 weeks for 3 cycles after a gossypol acetate lead-in period, according to the study protocol.; Other Names: IBI308; PD-1 inhibitor; Drug: Gossypol Acetate; Gossypol acetate 20 mg will be administered orally once daily after dinner for 9 weeks, according to the study protocol.; Other Names: Compound Gossypol Acetate Tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate	Objective response rate is defined as the proportion of participants who achieve complete response or partial response as their best overall response, as assessed according to RECIST version 1.1 by independent radiologic review.	At Week 11 after initiation of study treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Control Rate	Disease control rate is defined as the proportion of participants who achieve complete response, partial response, or stable disease as their best overall response according to RECIST version 1.1.	At Week 11 after initiation of study treatment
Progression-Free Survival	Progression-free survival is defined as the time from the first dose of study treatment to the first documented disease progression according to RECIST version 1.1 or death from any cause, whichever occurs first.	From the first dose of study treatment up to 24 months
Overall Survival	Overall survival is defined as the time from the first dose of study treatment to death from any cause.	From the first dose of study treatment up to 24 months
Duration of Response	Duration of response is defined as the time from the first documented complete response or partial response to disease progression or death from any cause, whichever occurs first.	From the first documented response up to 24 months
Adverse events (AEs) were graded according to the NCI CTCAE version 5.0	Adverse events, serious adverse events, treatment-related adverse events, and immune-related adverse events will be assessed and graded according to NCI CTCAE version 5.0.	From the first dose of study treatment through 30 days after the last dose of study treatment

Collaborators and Investigators

• Sponsor: Peking University People's Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): July 15, 2026
• Primary Completion (Estimated): September 15, 2027
• Study Completion (Estimated): September 15, 2029

Study Registration Dates

• First Submitted: June 15, 2026
• First Submitted That Met QC Criteria: June 15, 2026
• First Posted (Actual): June 18, 2026

Study Record Updates

• Last Update Posted (Actual): June 18, 2026
• Last Update Submitted That Met QC Criteria: June 15, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: colorectal cancer; immunotherapy; metastatic colorectal cancer; PD-1 inhibitor; sintilimab; pMMR/MSS; gossypol acetate; LRPPRC
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Colorectal Neoplasms; Antineoplastic Agents, Immunological; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Organic Chemicals; Pharmacologic Actions; Chemical Actions and Uses; Therapeutic Uses; Hydrocarbons; Terpenes; Sesquiterpenes; Immune Checkpoint Inhibitors; sintilimab; Gossypol
• Other Study ID Numbers: 2025PHD051-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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