TRIUNITE-02: A phase 2, open-label, randomized study of neoadjuvant CAPEOX plus tislelizumab and chidamide versus CAPEOX alone in previously untreated, resectable, locally advanced mismatch repair-proficient/microsatellite stable colon cancer.

TPS261 Background: The perioperative management of LACC aims to reduce the risk of local recurrence and distant metastasis. However, the clinical benefits of neoadjuvant chemotherapy alone remain limited. In the FOxTROT trial, CAPEOX yielded a pathological complete response (pCR) rate of merely 5-7%. Many clinical studies are being conducted to explore the rational combinations of immunotherapy with immunostimulation treatment including chemotherapy, targeted therapy and epigenetic modulators. Notably, the Capability-01 study (a phase II trial of Chidamide combined with targeted therapy and immunotherapy) demonstrated significant antitumor activity and a manageable safety profile in both metastatic colorectal cancer and neoadjuvant settings for breast cancer. Based on these findings, the ongoing phase II TRIUNITE-02 trial is investigating the triplet regimen of CAPEOX, a PD-1 inhibitor Tislelizumab, and the histone deacetylase inhibitor (HDACi) Chidamide as neoadjuvant therapy for LACC, with the primary objective of substantially increasing pCR rates and long-term survival outcomes. Methods: TRIUNITE-02 is a multicenter, open-label, randomized phase II trial evaluating a novel neoadjuvant regimen for LACC. A total of 100 eligible patients with clinically staged LACC (T3 with extramural spread into the mesocolic fat >5 mm or T4, N+) confirmed by a multidisciplinary team (MDT) are randomized in a 1:1 ratio to the experimental or control arm, stratified by sex (male vs. female), tumor location (left- vs. right-sided colon), and CEA level (5 vs. <5 ng/ml). Patients in the control arm receive four cycles of neoadjuvant CAPEOX. The experimental arm receives the same CAPEOX regimen combined with oral Chidamide (20 mg PO BID on days 1-14, Q3W) and intravenous Tislelizumab (200 mg IV on day 1, Q3W) for four cycles. Following neoadjuvant therapy, all patients undergo surgical resection eligibility assessment, and postoperative treatment is determined by the MDT. The Primary endpoint is the pCR rate, Secondary endpoints include major pathological response (MPR), objective response rate (ORR), tumor regression grade (TRG), R0 resection rate, progression-free survival (PFS), and overall survival (OS). This trial innovatively integrates an HDACi with chemoimmunotherapy to enhance neoadjuvant efficacy and improve long-term survival in LACC. Clinical trial information: NCT06709885 .