A phase Ib trial on the safety and feasibility of low-dose radiotherapy combined with immunochemotherapy for colorectal cancer with liver-limited metastasis (TRIUNITE-04).

TPS272 Background: Liver metastasis is the leading cause of death in patients with CRC. Despite significant progress in therapeutic techniques, the overall survival of patients with colorectal liver metastasis (CRLM) remains very low. Moreover, patients that receive chemotherapy and targeted therapy tend to develop drug resistance over time owing to inherent or acquired resistance. More effective and durable treatment strategies are needed for CRLM patients. Studies have demonstrated that a proportion of patients with high microsatellite instability or deficient mismatch repair (MSI-H/dMMR) mCRC responds well to immunotherapy. However, patients with MSS/pMMR mCRC almost showed no response to immunotherapy primarily due to the immunosuppressive properties of the hepatic tumor microenvironment (TME). Many studies have reported that LDRT can reprogram the TME of immune-desert tumors by augmenting T-cell infiltration and, combined with immunotherapy, induce mobilization of innate and adaptive immunity. The optimal radiation dose regimen remains unclear. Therefore, we initiated this early-phase trial to assess the safety and feasibility of LDRT combined with immunochemotherapy in patients with MSS/pMMR CRLM. Methods: The TRIUNITE-04 study is a single-arm, phase Ib trial Conducted in Daping Hospital, Army Medical University. The study will enroll 9-18 CRLM patients aged 18-80 years who are diagnosed with MSS/pMMR CRLM (cT3-4NxM1 or TXN1-2M1). Patients will receive LDRT of 10 Gy in 5 fractions, 15 Gy in 5 fractions, 20 Gy in 10 fractions respectively in our three groups on liver metastasis from Day 1 (patients with rectal cancer will receive SCRT concurrently), followed by Xelox, including Capecitabine (1000mg/m2 bid, d1-14, p.o, Q3W) and oxaliplatin (130mg/m2, d1, i.v, Q3W), and Tislelizumab (130mg/m2, d1, i.v, Q3W) starting from 1 week after the completion of radiation. The immunochemotherapy will be given for 2-4 cycles. The primary endpoints are safety and tolerability. Secondary objectives include ORR, R0 resection rate, PFS, OS. The sample size was based on the 3+3 design rules with 3-6 patients per dose level. Therefore, 9-18 patients will be enrolled. Clinical trial information: NCT06848465 .