Fruquintinib combined with sintilimab and SOX as conversion therapy for unresectable locally advanced or metastatic gastric/gastroesophageal junction adenocarcinoma (GC/GEJC): A single-arm, open-label, phase 2 clinical trial.

person Fei Ma Surgical Oncology, Henan Cancer Hospital/Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China info_outline Fei Ma, Suxia Luo, Bin Zhang, Qi Ma, Sheqing Ji, Zhandong Zhang, Yonglei Zhang, Wei Yang, Liangqun Peng, Dandan Guo, Jinjun Ren, Yuan Zhang, Yueyue Su, Jing Li, Wentao Liu, Jinxi Huang, Weiwei Yuan

Authors person Fei Ma Surgical Oncology, Henan Cancer Hospital/Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China info_outline Fei Ma, Suxia Luo, Bin Zhang, Qi Ma, Sheqing Ji, Zhandong Zhang, Yonglei Zhang, Wei Yang, Liangqun Peng, Dandan Guo, Jinjun Ren, Yuan Zhang, Yueyue Su, Jing Li, Wentao Liu, Jinxi Huang, Weiwei Yuan Organizations Surgical Oncology, Henan Cancer Hospital/Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China, Henan Cancer Hospital, Zhengzhou, China, Radiology, 3rd Affiliated Hospital of ZhengZhou University, Zhengzhou, China, Radiology, Henan Cancer Hospital/Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China Abstract Disclosures Research Funding No funding sources reported Background: The evidence of conversion therapy for unresectable GC/GEJC is limited. Fruquintinib is an oral, highly selective VEGFR 1/2/3 inhibitor that has synergistic antitumor effects when combined with ICIs/chemotherapy. This study was conducted to evaluate the efficacy and safety of fruquintinib combined with sintilimab and SOX as a conversion therapy in patients (pts) with initially unresectable locally advanced or metastatic GC/GEJC. Methods: Eligible pts received 3 to 6 cycles of fruquintinib (4mg/d, po, qd, d1-14) combined with sintilimab (200mg, iv, d1), oxaliplatin (130 mg/m 2 , iv, d1) and S-1 (40-60mg based on BSA, po, bid, d1-14) every 3 weeks. One more cycle of sintilimab plus SOX was given before resection. Radiographic assessments were performed every 3 cycles and MDTs were employed to determine surgical feasibility. Primary endpoint was R0 resection rate. Secondary endpoints included pathological response, ORR, PFS, OS, and safety. Results: From May 2022 to December 2023, 34 pts (29 males/5 females) with a median age of 62 years (range: 43–76), 71% ECOG PS1, 59% GEJC were enrolled. The unresectable factors included liver metastasis 15% (5/34), peritoneal metastasis 6% (2/34), para-aortic lymph node metastasis 3% (1/34), extensive or bulky lymph nodes 53% (18/34), and local progression 38% (13/34). Five pts had more than one unresectable factors. The ORR and DCR of 29 pts who had at least one preoperative assessment were 65.5% (19 PR) and 96.6%, respectively. Among the 18 pts who had completed surgical conversion, all of them had R0 resection (100%), 2 pts (11.1%) achieved pathological complete response (pCR), and 1 pt reached AJCC-TRG1. The pathological response rate (pRR) according to JCGC (≥ Grade 1b) was 100% (18/18). Additionally, downstaging to pN0 was achieved in 13 pts (72.2%). During preoperative treatment, treatment-emergent adverse events (TEAEs) occurred in 85.3% (29/34) pts, and most events were grade 1–2. Grade 3 TEAEs included 2 cases of neutrophil count decreased, and 1 case of each (platelet count decreased, anemia, diarrhea, and immune-related pneumonitis). No severe surgery-related complication was observed. Conclusions: Fruquintinib combined with sintilimab and SOX as a conversion therapy strategy shown acceptable toxicity in unresectable GC/GEJC and induced very high R0 resection, pathological response, and downstaging rate. The study is ongoing, more data will be disclosed in the future. Clinical trial information: NCT05177068.

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