98P Short-course radiotherapy based total neoadjuvant therapy combined with tislelizumab in the treatment of locally advanced rectal cancer: Mid-term report of a phase II, open-label, randomized controlled trial

Short-course radiotherapy (SCRT) based Total Neoadjuvant Therapy (TNT) has been used for the treatment of locally advanced rectal cancer (LARC). However, studies show that the pCR rate of patients still hovers around 20%. It has been found that radiation therapy possess synergistic anticancer effects with immune checkpoint inhibitor therapy by altering the tumor immune microenvironment (TIME). Therefore, this phase II clinical trial (ClinicalTrials.gov identifier: NCT05086627) we aimed to evaluate the efficacy and safety of SCRT based TNT combined with tislelizumab in LARC patients. This is a prospective, open-label, single-center, phase II randomized controlled trial. Patients initially diagnosed with rectal cancer cT1-2N+M0 or cT3-4NanyM0 were recruited and underwent total mesorectal excision (TME) surgery after completing neoadjuvant therapy. Control group patients received SCRT (25Gy/5f) followed by four cycles of CapeOX. And trial group patients received an additional intravenous infusion of 200mg tislelizumab on the first day of each cycle of CapeOX. Mismatch repair (MMR) and microsatellite instability (MSI) tests were performed in all cases. Adverse events (AEs) were recorded and follow-up was performed for 36 months. The pathological complete response (pCR) rate was set as the primary endpoint, and the major pathologic response (MPR, TRG0+TRG1), 3-year PFS, 3-year OS and treatment safety were set as the secondary endpoints. A total of 63 patients were recruited, of which 49 completed the study protocol, including 23 in the control group and 26 in the trial group. All patients had pMMR/MSS status except for 1 patient with pMMR/MSI-H. In the control group, 22 patients received surgical treatment, and 6 patients achieved pCR (26.09%). In the trial group, 25 patients received surgical treatment, and 16 patients achieved pCR (61.54%). SCRT based TNT combined with tislelizumab followed by TME surgery exhibited a favorable pCR in LARC. A multicenter, double-blind, randomized controlled trial is warranted.