Combination of High and Low-Dose Radiotherapy With Immune Therapy and TKI in Advanced Colorectal Cancer: A Phase II Study (TRIUNITE-07)

Efficacy of Combined High and Low-Dose Radiotherapy With Immune Therapy and Tyrosine Kinase Inhibitors (TKI) as a Second-Line or Later Treatment Strategy for Advanced Colorectal Cancer: A Single-Arm, Open-Label Phase II Study

The goal of this clinical trial is to learn whether a high- and low-dose radiotherapy regimen followed by anti-angiogenic TKI and anti-PD-1 antibody therapy works to treat advanced metastatic colorectal cancer. It will also evaluate long-term survival outcomes and explore potential biomarkers associated with tumor response and immune modulation.

The main questions it aims to answer are:

Does the high- and low-dose radiotherapy regimen followed by sequential anti-angiogenic TKI and anti-PD-1 therapy improve the objective response rate (ORR) in patients with advanced metastatic colorectal cancer?

What are the disease control rate (DCR) and survival outcomes following this treatment strategy?

Are tumor response and long-term survival associated with specific biomarkers related to systemic immune modulation induced by radiotherapy to different metastatic organs?

How does this radiotherapy pattern affect tumor immune infiltration in metastatic lesions?

This is a single-arm, single-center, prospective Phase II clinical study designed to evaluate the efficacy of a high- and low-dose radiotherapy regimen targeting metastatic lesions followed by sequential anti-angiogenic TKI and anti-PD-1 antibody therapy in patients with advanced metastatic colorectal cancer.

Participants will:

Receive high- and low-dose radiotherapy to metastatic lesions. Subsequently receive anti-angiogenic TKI combined with anti-PD-1 antibody therapy.

Undergo regular clinical assessments and imaging evaluations to determine tumor response.

Provide blood and tumor samples for biomarker and immune infiltration analysis. Be followed for survival outcomes and disease progression.

Study Overview

• Status: Not yet recruiting
• Conditions: Immune Response; Refractory Colorectal Cancer; Radiotherapy-Induced Immune Priming
• Intervention / Treatment: Radiation: High- and Low-Dose Radiotherapy; Drug: Anti-Angiogenic TKI and Anti-PD-1 Therapy

• Study Type: Interventional
• Enrollment (Estimated): 33
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Chuan Chen, Professor; Phone Number: 18084012018; Email: cxq13396083059@163.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Ability to understand and willingness to sign a written informed consent form.
2. Age 18-80 years, male or female.
3. Histologically confirmed microsatellite stable (MSS) / proficient mismatch repair (pMMR) colorectal adenocarcinoma.

4. Clinical stage IV disease confirmed by systemic imaging. At least two measurable metastatic lesions per RECIST 1.1, including:

   At least one lesion ≥2 cm in diameter and at least one lesion <2 cm in diameter;

   For lesions within the same organ, at least one lesion ≥2 cm and one lesion <2 cm must be located within independent, non-overlapping radiation fields;

   For lesions in different organs, high-dose and low-dose radiotherapy should preferably be delivered to lesions in different organs.

   Second-line or later treatment setting, defined as disease progression after prior platinum- and irinotecan-based chemotherapy, including:

5. Failure after first-line triplet chemotherapy containing platinum and irinotecan; Or failure after first-line platinum-based chemotherapy followed by second-line irinotecan-based chemotherapy.
6. Ability to swallow oral medication.
7. ECOG performance status 0-1.
8. Adequate organ function as defined by laboratory criteria.

Exclusion Criteria:

Diffuse miliary liver or lung metastases, or bulky metastatic lesions ≥10 cm in diameter.

Presence of brain metastases.

1. History of severe hypersensitivity to monoclonal antibodies or anti-angiogenic agents.
2. Prior exposure to immune checkpoint inhibitors (including anti-PD-1, anti-PD-L1, anti-CTLA-4 antibodies), immune checkpoint agonists (e.g., targeting ICOS, CD40, CD137, GITR, OX40), or any prior cancer immunotherapy.
3. Active autoimmune disease or history of autoimmune disease, including but not limited to interstitial pneumonitis, colitis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, or hypothyroidism (patients on stable hormone replacement therapy may be eligible). Patients with psoriasis or childhood asthma/allergy that has completely resolved and requires no adult intervention may be eligible; patients requiring bronchodilator therapy are excluded.
4. History of immunodeficiency, including positive HIV test, congenital or acquired immunodeficiency, prior organ transplantation, or allogeneic bone marrow transplantation.

5. Uncontrolled cardiovascular disease, including:

   NYHA class II or higher heart failure;

6. Unstable angina;
7. Myocardial infarction within 1 year;
8. Clinically significant uncontrolled supraventricular or ventricular arrhythmias.
9. Severe infection (CTCAE grade >2) within 4 weeks prior to first study treatment, including severe pneumonia, bacteremia, or infection requiring hospitalization. Active pulmonary inflammation on baseline imaging, signs or symptoms of infection within 14 days before treatment requiring systemic antibiotics (except prophylactic antibiotics), or active tuberculosis (current or within 1 year without adequate treatment).
10. Active hepatitis B (HBV DNA ≥2000 IU/mL) or active hepatitis C (positive HCV antibody with detectable HCV RNA above the lower limit of detection).
11. Diagnosis of another malignancy within 5 years prior to first study treatment, except for malignancies with low risk of metastasis or death (5-year survival rate >90%), such as adequately treated basal cell carcinoma, squamous cell carcinoma of the skin, or carcinoma in situ of the cervix.
12. Pregnant or breastfeeding women.

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: High- and Low-Dose Radiotherapy Followed by Sequential Anti-Angiogenic TKI and Anti-PD-1 Therapy

Radiation: High- and Low-Dose Radiotherapy; Participants will receive a stratified high- and low-dose radiotherapy regimen to metastatic lesions based on lesion size, followed by sequential anti-angiogenic tyrosine kinase inhibitor (TKI) and anti-PD-1 antibody therapy. Metastatic lesions with a maximum diameter ≤2 cm will be treated with stereotactic body radiotherapy (SBRT) at 8 Gy per fraction for 3 consecutive fractions (total dose 24 Gy) prior to initiation of the first cycle of targeted and immunotherapy. The total cumulative volume of lesions treated with SBRT will not exceed 100 cm². Metastatic lesions with a maximum diameter >2 cm will receive low-dose radiotherapy (LDRT) at 3 Gy per fraction for 5 fractions. LDRT will be administered rhythmically, with one fraction delivered prior to each cycle of targeted and immunotherapy, for a total of five fractions. The total cumulative volume of lesions treated with LDRT will not exceed 500 cm². Within 7 days after completion of radiotherapy, participants will initiate systemi; Drug: Anti-Angiogenic TKI and Anti-PD-1 Therapy; Participants will receive systemic therapy consisting of an oral anti-angiogenic tyrosine kinase inhibitor (TKI) in combination with an intravenous anti-PD-1 monoclonal antibody. The anti-angiogenic TKI will be administered orally according to the approved dosing schedule. The anti-PD-1 antibody will be administered intravenously at standard dosing intervals. Treatment will begin within 7 days after completion of radiotherapy and will continue until disease progression, unacceptable toxicity, withdrawal of consent, or investigator decision. Safety will be monitored throughout treatment, and adverse events will be graded according to CTCAE version 5.0.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Objective Response Rate (ORR)	At the end of 2 treatment cycles (approximately 6-8 weeks after treatment initiation)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Control Rate (DCR)	Disease Control Rate is defined as the proportion of participants achieving Complete Response (CR), Partial Response (PR), or Stable Disease (SD) according to RECIST version 1.1.	At the end of 2 treatment cycles (approximately 6-8 weeks after treatment initiation).
Progression-Free Survival (PFS)		From the first radiotherapy treatment until disease progression or death, assessed up to 24 months
Overall Survival (OS)		From the first radiotherapy treatment until death from any cause, assessed up to 24 months.

Collaborators and Investigators

• Sponsor: Daping Hospital and the Research Institute of Surgery of the Third Military Medical University

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): April 1, 2029

Study Registration Dates

• First Submitted: March 4, 2026
• First Submitted That Met QC Criteria: March 9, 2026
• First Posted (Actual): March 12, 2026

Study Record Updates

• Last Update Posted (Actual): March 12, 2026
• Last Update Submitted That Met QC Criteria: March 9, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• 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; Therapeutics; Radiotherapy
• Other Study ID Numbers: DP2025476

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