Chemoradiotherapy (CRT) followed by sequential tislelizumab (TIS) + CAPOX and TIS monotherapy for organ preservation in locally advanced low rectal cancer.

TPS315 Background: CRT followed by total mesorectal excision (TME) is the standard care for patients with locally advanced low rectal cancer (≤ 5cm from the anal margin). However, TME may lead to permanent colostomy and severely impact quality of life. Organ preservation is, therefore, a critical unmet need for these patients. The proportion of patients achieving clinical complete response (cCR) after CRT is relatively low, with the literature reporting around 20%. Total neoadjuvant therapy (TNT) has been investigated to increase cCR rate. Several clinical trials demonstrated that PD-1 inhibitor combined with TNT could result in significate improvement in pathological complete response rate (pCR rate, 39.8% vs 15.3%, p < 0.001 in UNION study) or complete response rate (pCR+cCR rate, 44.8% vs 26.9%, p = 0.031 in a randomized phase 2 study) compared with TNT alone in rectal cancer patients. The RELIEVE-01 study (NCT06390982) was designed to evaluate the efficacy in organ preservation with CRT followed by sequential TIS + CAPOX and TIS monotherapy in patients with low rectal cancer. Methods: This multicenter, single-arm, phase 2 study will enroll 46 pts with histopathologically confirmed rectal adenocarcinoma (≤ 5cm from the anal margin), pMMR/MSI-L/MSS, cT1-3N1M0/T2-3N0M0, and ECOG PS ≤1. Pts will initially receive 6 weeks of CRT (50.4 Gy/28F, capecitabine 825 mg/m 2 , bid, d1-5 each week), followed by 4 cycles of TIS + CAPOX (TIS, 200 mg, IV, d1; capecitabine 1000 mg/m 2 , bid, d1-14; oxaliplatin 130 mg/m 2 , d1) in a 21-day cycle. Then, clinical response will be assessed to determine the subsequent treatment. Patients with cCR will receive TIS + CAPOX (4 cycles) and TIS (up to 9 cycles), and then be managed using the W&W strategy. Patients with non-cCR will undergo TME. Patients with near-cCR will be given local excision, and those achieving pCR will receive the same treatment as cCR patients, and for those with non-pCR after local excision, TME will be performed. The primary endpoint is rate of CR (cCR plus pCR post local resection). Secondary endpoints include organ-preserving rate, event-free survival rate and OS rate at 1, 2 and 3 years, respectively. Recruitment is ongoing. Clinical trial information: NCT06390982 .