537P - Stereotactic ablative radiotherapy combined with fruquintinib and tislelizumab in metastatic colorectal cancer: Updated findings from a single-arm, prospective phase II trial (RIFLE)

Background

Stereotactic ablative radiotherapy (SABR) has been shown to sensitize immunotherapy through inducing immunogenic death and remodeling the tumor immune microenvironment. Anti-angiogenic therapy exhibits synergistic antitumor effects with PD-1 antibodies through its immunomodulatory effects for metastatic colorectal cancer (mCRC) patients. Here, we report the updated findings from RIFLE trial: the efficacy and safety of the combination of fruquintinib, PD-1 inhibitor tislelizumab and SABR in mCRC patients.

Methods

RIFLE is a single-center, single-arm, prospective phase II clinical trial (NCT04948034). mCRC patients with at least 2 measurable lesions who have failed ≥ 1L standard therapy will receive SABR followed by fruquintinib (5 mg, d1-14, qd) and tislelizumab (200 mg, d1, q3w) within two weeks from completion of radiation. The primary endpoint is the objective response rate (ORR). The secondary endpoints include disease control rate (DCR), duration of response (DoR), progression-free survival (PFS) rate, overall survival (OS) rate and toxicity.

Results

From August 2021 to April 2024, 38 patients were included and 35 in the efficacy analysis. Median age was 59 years, 27 (77.1%) patients were male, 30(85.7%) had ≥ 3 metastases, and 16 (45.7%) had received ≥ 3 prior lines of systemic therapy. The biological effective dose (BED) for irradiated lesions ranged from 37.5 to 105 Gy. Median study follow-up was 17.8 months (95%CI:12.101-23.499), 1 patient achieved complete response (CR) for target lesions, 11 partial response (PR), 15 stable disease (SD), illustrating an ORR of 34.3% and a DCR of 77.1%. Median PFS was 8.8 months (95%CI：6.200-11.400). The most common treatment-related adverse events (TRAEs) were proteinuria (34.3%), hypertension (22.9%) and rash (17.1%). Grade 3-4 AEs occurred in 9 patients, including proteinuria and hypertension, and there were no treatment-related deaths.

Conclusions

SABR combined with tislelizumab and fruquintinib shows promising effects and good safety in the treatment of metastatic colorectal cancer, which is expected to provide new therapeutic strategies and improve the prognosis for mCRC patients.

Clinical trial identification

NCT04948034, FDRT-2020-274-2194. Initial Release: 06/23/2021.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Hutchison MediPharma Co., Ltd and BeiGene (Beijing) Co., Ltd.

Disclosure

All authors have declared no conflicts of interest.