FAPI-Guided Radiotherapy With Cadonilimab and Standard Chemotherapy for Colorectal Peritoneal Metastasis: A Phase III Randomized Controlled Trial (TORHC-PM02) (TORCH-PM02)

FAPI-Guided Hypofractionated Radiotherapy Combined With Cadonilimab and Standard Second-Line Chemotherapy Versus Standard Second-Line Chemotherapy for Peritoneal Metastasis From Colorectal Cancer: A Multicenter, Randomized, Open-Label, Phase III Trial (TORHC-PM02)

The goal of this clinical trial is to test whether adding targeted radiation plus cadonilimab immunotherapy to standard second-line chemo works better for adults with colorectal cancer only spread to the peritoneum, and check how safe this combined treatment is. Its main research questions are:

Does the combined treatment slow cancer growth for a longer time than standard chemo alone? What side effects will participants get from the new combination therapy? Researchers will compare the chemo-radiation-immunotherapy combination against standard chemo alone to see if the new plan shrinks tumors and improves outcomes.

Participants will:

Receive either the new combined treatment or standard chemo chosen randomly by chance Visit the hospital regularly for drug infusions, scans and physical exams Complete questionnaires about daily quality of life and report any discomfort

Study Overview

• Status: Not yet recruiting
• Conditions: Immunotherapy; Radiation Therapy; Second-line Treatment; Colon Rectal Cancer Adenocarcinoma; Peritoneal (Metastatic) Cancer
• Intervention / Treatment: Drug: Second-Line Chemotherapy; Radiation: Radiation Therapy; Drug: Cadonilimab (AK104)

• Study Type: Interventional
• Enrollment (Estimated): 198
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Zhen Zhang, MD, PhD; Phone Number: 18801735029; Email: zhen_zhang@fudan.edu.cn

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200032
      • Fudan University Shanghai Cancer Center
      • Contact: Zhen Zhang, Prof.; Phone Number: +8618017312301; Email: zhenzhang_@fudan.edu.cn
      • Contact: Zhiyuan Zhang, M.D.; Phone Number: +86 18916733704; Email: zhangzhiyuan.1994@163.com
      • Principal Investigator: Zhen Zhang, Ph.D, M.D.
      • Principal Investigator: Guoxiang Cai, Ph.D, M.D.

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Histopathologically confirmed colorectal adenocarcinoma.
2. Tumors confirmed pMMR by immunohistochemistry or MSI-L/MSS via gene sequencing.
3. Metastases limited to peritoneum only, no metastases in other organs.
4. No moderate or massive ascites; only trivial physiological effusion without drainage requirement.
5. No symptomatic intestinal obstruction and no obstructive signs on imaging; patients can take food normally.
6. Baseline CT/MRI confirms peritoneal metastases.
7. Positive baseline FAPI PET/CT: at least one peritoneal mass lesion with long diameter ≥1 cm and markedly elevated SUVmax suitable for radiotherapy contouring.
8. At least one measurable lesion per RECIST v1.1 criteria.
9. Progression after first-line standard systemic therapy (FOLFOX/XELOX ± targeted agents); no prior second-line treatment received.
10. Peritoneal recurrence within 1 year after adjuvant fluoropyrimidine-based chemotherapy.
11. No moderate or massive ascites; only trivial physiological effusion without drainage requirement.
12. Voluntarily sign written informed consent and comply with scheduled study visits and treatment procedures.

Exclusion Criteria:

1. Prior exposure to any anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody or other agents targeting T-cell co-stimulatory/checkpoint pathways.
2. Moderate or massive ascites requiring clinical intervention.
3. Partial or complete symptomatic intestinal obstruction.
4. Pregnant or breastfeeding women.
5. History of high-dose abdominal radiotherapy that prevents re-irradiation.
6. Diffuse miliary peritoneal metastases on FAPI PET/CT without definable target volume for radiotherapy.
7. Active autoimmune diseases (systemic lupus erythematosus, rheumatoid arthritis, etc.); systemic corticosteroids or other immunosuppressants required within 14 days before enrollment; severe underlying vital organ disease judged unsuitable for immunotherapy by investigators.
8. Poor compliance or other conditions judged inappropriate for study participation by investigators.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Chemo-immunotherapy plus FAPI-guided radiotherapy; Participants receive standard second-line chemotherapy combined with cadonilimab immunotherapy given every two weeks. They also receive hypofractionated radiotherapy guided by FAPI PET/CT to treat peritoneal tumor masses. Radiation doses are adjusted to protect the small intestine. After every eight weeks of treatment, a multidisciplinary team assesses whether surgery is possible. Treatment continues until cancer worsens or side effects become too severe to tolerate.	Drug: Second-Line Chemotherapy; All chemotherapy agents are given by intravenous infusion every 2 weeks with oxaliplatin, leucovorin and continuous infusion fluorouracil, or irinotecan, leucovorin and continuous infusion fluorouracil. Targeted agents bevacizumab or cetuximab can be added per investigator's clinical judgment. Dose adjustments are allowed for myelosuppression, gastrointestinal or other toxicities.; Radiation: Radiation Therapy; Radiation target volumes are contoured on fused FAPI PET/CT images for peritoneal masses ≥1 cm. Fraction doses range from 5 Gy to 25 Gy over 5 fractions, modified to meet small intestine organ-at-risk constraints. Radiation is delivered within the first 8 weeks of combined chemoimmunotherapy treatment.; Drug: Cadonilimab (AK104); Cadonilimab is a PD-1/CTLA-4 dual-target biologic agent. The fixed dose of 6 mg/kg is infused intravenously once every 2 weeks alongside chemotherapy. Dose delay or permanent discontinuation will be applied for grade 3-4 immune-related adverse events that do not improve with immunosuppressive treatment.
Active Comparator: Standard second-line chemotherapy only; Participants receive standard second-line chemotherapy every two weeks. No immunotherapy or radiation treatment is provided in this group. Treatment continues until cancer worsens or side effects become too severe to tolerate. Tumor assessment will be performed after 8 weeks of therapy, a multidisciplinary team assesses whether surgery is possible. Treatment continues until cancer worsens or side effects become too severe to tolerate.	Drug: Second-Line Chemotherapy; All chemotherapy agents are given by intravenous infusion every 2 weeks with oxaliplatin, leucovorin and continuous infusion fluorouracil, or irinotecan, leucovorin and continuous infusion fluorouracil. Targeted agents bevacizumab or cetuximab can be added per investigator's clinical judgment. Dose adjustments are allowed for myelosuppression, gastrointestinal or other toxicities.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS)	Time from randomization to first documentation of tumor progression (including enlargement of target lesions, new distant metastases, or new onset of ascites) or death from any cause, whichever occurs first, assessed per RECIST v1.1.	Up to 36 months after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	Survival duration from randomization until death from any cause.	OS is defined from randomization until death from any cause up to 36 months.
Objective Response Rate (ORR)	The best overall tumor response rate, defined as the proportion of participants achieving confirmed complete response or partial response assessed via imaging based on RECIST 1.1 criteria and verified by multidisciplinary team review.	The best overall tumor response will be assessed every 8 weeks after the participant begins study treatment by scheduled MDT assessment through study completion, up to 36 months.
Disease Control Rate (DCR)	The best overall disease control rate, defined as the proportion of participants with confirmed complete response, partial response or stable disease assessed via imaging based on RECIST 1.1 criteria and verified by multidisciplinary team review.	The best overall disease control rate will be assessed every 8 weeks after the participant begins study treatment by scheduled MDT assessment through study completion, up to 36 months.
Treatment-related adverse events	Incidence and severity of treatment side effects graded by NCI CTCAE v6.0.	Side effects will be recorded from the participant's first study treatment dose with radiotherapy and system treatment every cycle to 30 days after their final study treatment dose through study completion, up to 36 months.
Quality of life( QoL)	Patient self-assessment via EORTC QLQ-C30 questionnaire to monitor changes in quality of life throughout treatment.	At baseline and radiotherapy period will be reorded once, at system treatments QoL will be reported and recorded every 8 weeks regularly during the treatment through study completion, up to 36 months.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Peritoneal Cancer Index (PCI)	PCI score reflecting peritoneal tumor burden is measured on FAPI PET/CT images to observe tumor load variations.	At baseline and every 8 weeks fixed assessment time points during treatment by scheduled MDT assessment through study completion, up to 36 months.

Collaborators and Investigators

• Sponsor: Fudan University

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): August 1, 2030
• Study Completion (Estimated): March 1, 2031

Study Registration Dates

• First Submitted: September 1, 2026
• First Submitted That Met QC Criteria: September 8, 2026
• First Posted (Actual): September 11, 2026

Study Record Updates

• Last Update Posted (Actual): September 11, 2026
• Last Update Submitted That Met QC Criteria: September 8, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Keywords: Radiation Therapy; Colorectal Peritoneal Metastasis; Fapi; TORCH-PM02
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplastic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms; Neoplasm Metastasis; Therapeutics; Radiotherapy
• Other Study ID Numbers: FDRT-2026-426-5278

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