Radiotherapy Combined QL1706, TAS-102 and Bevacizumab in mCRC

A Single-Arm, Exploratory Study of Palliative Radiotherapy Combined With Iparomlimab and Tuvonralimab, Trifluridine/Tipiracil (TAS-102), and Bevacizumab in Later-Line Treatment of Advanced Colorectal Cancer

This single-center, single-arm, prospective study plans to enroll patients with advanced colorectal cancer who have failed first-line or higher systemic therapies. Participants will receive a combination of iparomlimab and tuvonralimab (QL1706), trifluridine/tipiracil (TAS-102), bevacizumab, and palliative radiotherapy. The efficacy and safety of this combination therapy will be evaluated by assessing objective response rate (ORR), progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and safety profile.

Study Overview

• Status: Not yet recruiting
• Conditions: mCRC
• Intervention / Treatment: Radiation: Palliative radiotherapy; Drug: Iparomlimab and tuvonralimab; Drug: TAS-102; Drug: Bevacizumab

• Study Type: Interventional
• Enrollment (Estimated): 37
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yawen Zhen, Associate Director, Department of Oncology; Phone Number: +86 150 2001 0760; Email: my123454321@126.com

Study Locations

• China
  • Shandong
    • Jinan, Shandong, China, 250000
      • Jinan Central Hospital
      • Contact: Yawen Zhen, Associate Director, Department of Oncology; Phone Number: +86 150 2001 0760; Email: my123454321@126.com
      • Principal Investigator: Meili Sun, Director, Department of Oncology, MD, PhD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Aged 18 to 75 years .
• Histologically confirmed unresectable colorectal adenocarcinoma.
• Patients must have received at least one prior line of oxaliplatin-, irinotecan-, or 5-FU-based therapy with documented progression or intolerance.
• Documented KRAS and BRAF mutation status (mutant or wild-type) must be available.
• Palliative radiotherapy targeting primary or metastatic lesions is planned.
• At least one measurable lesion per RECIST v1.1 exists.
• ECOG score of 0-1 and life expectancy ≥12 weeks.
• Adequate bone marrow, hepatic, and renal function must be demonstrated.
• Fertile patients commit to using effective contraception during and for 6 months post-treatment.

Exclusion Criteria:

• History of Grade ≥3 immune-related adverse events (irAEs) from prior immunotherapy deemed contraindications for retreatment.
• Radiation or systemic anticancer therapy within 14 days prior to first study treatment.
• Active CNS metastases and/or leptomeningeal disease (LMD). Symptomatic interstitial lung disease (ILD), active pneumonitis, uncontrolled infections, or non-healing wounds/fistulae.
• Intestinal perforation risks: active diverticulitis, intra-abdominal abscess, GI obstruction, or cancer-related peritoneal carcinomatosis.
• Uncontrolled or symptomatic serous cavity effusions (pleural, ascites, pericardial).
• Uncontrolled cardiovascular/cerebrovascular diseases.
• Medical/social conditions that may compromise study results or lead to premature termination per investigator judgment.

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 Arm; Palliative radiotherapy combined with iparomlimab and tuvonralimab (QL1706), trifluridine/tipiracil (TAS-102), and bevacizumab.

Radiation: Palliative radiotherapy; Conventional fractionation, low-dose hypofractionated radiotherapy, or high-dose hypofractionated radiotherapy may be employed.; Drug: Iparomlimab and tuvonralimab; 5 mg/kg, intravenously infused on Day 1 of each cycle, administered every 3 weeks (with each cycle defined as 21 days).; Drug: TAS-102; 35 mg/m², orally twice daily on Days 1 to 5 and Days 8 to 12 of each cycle, with each cycle spanning 28 days (4 weeks).; Drug: Bevacizumab; 7.5 mg/kg via intravenous infusion on Day 1 of each 21-day cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR	The time from the date for first documented response of complete response (CR) or partial response (PR) to the date of first documented of disease progression or death, whichever occurs first.	approximately 4 months after the last subject participating in

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OS	The time from the starting date of study drug to the date of death due to any cause.	approximately 12 months after the last subject participating in
PFS	the proportion of subjects with complete response (CR) and partial response (PR) according RESIST1.1 in total subjects.	approximately 12 months after the last subject participating in
DCR	The proportion of subjects with complete response (CR) and partial response (PR) and stable disease(SD) in total subjects	approximately 4 months after the last subject participating in
Safety (adverse event)	The rates of adverse events.	Up to approximately 2 years.

Collaborators and Investigators

• Sponsor: Jinan Central Hospital
• Investigators: Principal Investigator: Meili Sun, Director, Department of Oncology, MD, PhD,, Jinan Central Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): August 31, 2025
• Primary Completion (Estimated): August 31, 2027
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: August 6, 2025
• First Submitted That Met QC Criteria: August 6, 2025
• First Posted (Actual): August 11, 2025

Study Record Updates

• Last Update Posted (Actual): August 11, 2025
• Last Update Submitted That Met QC Criteria: August 6, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Antineoplastic Agents, Immunological; Antineoplastic Agents; Physiological Effects of Drugs; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Bevacizumab
• Other Study ID Numbers: 20250710004

Drug and device information, study documents

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