Short-course radiotherapy (SCRT) followed by fruquintinib plus adebrelimab and CAPOX in the total neoadjuvant therapy of locally advanced rectal cancer (LARC): A multicenter, single-arm, open-label, phase II study (UNION TNT).

• DOI: 10.1200/jco.2025.43.4_suppl.192
• Publication Date: 2025-01-27T14:28:59Z
• Authors: Zhenyu Lin; Peng Zhang; Lei Zhao; Hong Ma; Hongli Liu; Junli Liu; Ximing Xu; Dandan Lin; Zhen Zhang; Fan Xia; Kaixiong Tao; Tao Zhang
• Keywords: Short course; Neoadjuvant Therapy; Open label

192 Background: We have demonstrated that neoadjuvant SCRT followed by PD-1 inhibitor plus CAPOX for LARC patients (pts) showed a higher pCR rate and well-tolerated safety profile in phase III UNION study. Fruquintinib is potent highly selective VEGFR inhibitor, which had been approved previously treated mCRC pts. This study aimed to investigate the efficacy of fruquintinib adebrelimab as total therapy high-risk Methods: In this prospective, open-label, multi-centers, single-arm 2 (NCT06234007), pts diagnosed with newly high risk were recruited. Pts received (25Gy/5f) six cycles (4mg, qd, po, q3w,for initial 6 run-in period, dosage would be adjusted based on dose-limited toxicities 1st cycle) combined (1200mg, iv, d1, q3w) (q3w). Primary endpoint was CR (including clinical & pathologic CR). Secondary endpoints included 3-year EFS rate, OS, R0 resection safety. Results: As 30 Aug 2024, 45 enrolled (median age 59 years [range: 24-75], 26 males, 23 T4 stage 20 N2 stage, 36 EMVI positive, 31 MRF 22 tumor located ≤5cm from anal verge). Up Sep all completed SCRT, 73.33% (33/45), 57.78% (26/45) 31.11% (14/45) two, four combination therapy, respectively. At data cut-off, 33 analysis, 28 underwent MRI examination mrTRG results available, remaining 5 early surgery due AEs/serious AEs. 35.7% (10/28) 46.43% (13/28) classified mrTRG1 mrTRG2, Of 19 who surgery, achieved (100%) 12 (63.16%). Moreover, 1 pt cCR during thus treatment strategy provided 65% (1 divided 20). Grade 3/4 adverse effects (AEs) occurred 16 (47.06%), most commonly lymphocyte count decreased (n=6, 18.18%), diarrhea (n=5, 15.15%) AST increased (n=2, 6.06%). 4 serious AEs reported intestinal perforation after therapy. No related death reported. Conclusions: promising favorable pts, generally manageable. might potential option Updated will presented future. Clinical trial information: NCT06234007 .