Fruquintinib plus sintilimab and SOX as conversion therapy for initially unresectable gastric/gastroesophageal junction adenocarcinoma (GC/GEJC): Updated response and surgical results from a single-arm, phase 2 clinical trial.

Abstract

e16016 Background: Clinical evidence of conversion therapy for unresectable GC/GEJC is limited. We have reported the encouraging results of the ongoing open-label, phase 2 trial (NCT05177068) with promising R0 resection rate and acceptable tolerability in sintilimab plus fruquintinib and SOX treated unresectable GC/GEJC patients (pts) (ASCO GI 2025). Here we present updated results after enrollment completed. Methods: Eligible pts were administered fruquintinib (4mg/d, po, qd, d1-14), 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 for 3 or 6 cycles. One more cycle of sintilimab plus SOX was given before resection. Pts were assessed for tumor response and surgical feasibility by radiologic imaging & MDT every 3 cycles. Primary endpoint was R0 resection rate. Secondary endpoints included pathological response, ORR, PFS, OS, and safety. Results: As of Jan 3, 2025, 42 pts (37 males/5 females) with a median age of 64 years (range: 43–76), 71% ECOG PS 1, 55% GEJC were enrolled. Of the 36 cT4 pts at diagnosis, 13 (36.1%) were cT4b. Nine (21.4%) of the 42 pts had distant metastasis and five (11.9%) pts had more than one unresectable factors. The most common unresectable factors were extensive or bulky lymph nodes 54.8% (23), local progression 38.1% (16) and liver metastasis 11.9% (5). Of 41 evaluable pts, ORR was 73.2% and DCR was 97.6%. Among the 34 pts who had completed surgical conversion, the R0 resection rate was 100% (34/34) and R0 surgical conversion rate was 82.9% (34/41). 8.8% (3/34) pts achieved pathological complete response (pCR), and 20.6% (7/34) pts reached tumor regression grade (TRG) 0-1. Additionally, the pathological response rate (pRR) according to JCGC (≥ Grade 1b) was 94.1% (32/34). Of the 13 cT4b pts, ORR was 76.9%, DCR was 100.0% and 12 pts had completed surgical conversion. R0 surgical conversion rate was 92.3%, pCR was 8.3%, 25.0% pts reached TRG 0-1 and 58.3% pts reached pathological (p) N0. In 19 GC pts, ORR was 77.8%, DCR was 94.4%, R0 surgical conversion rate was 77.8%, 21.4% (3/14) pts reached TRG 0-1 and 28.6% pts reached pN0. Forty (95.2%) pts had treatment-emergent adverse events (TEAEs) and seven (16.7%) pts had grade 3 TEAEs, including 4 cases of anemia, 2 cases of neutrophil count decreased, and 1 case of each (lymphocyte count decreased, gastrointestinal hemorrhage, diarrhea, and immune-related pneumonitis). No new safety signal or severe surgery-related complication were observed. Conclusions: Fruquintinib combined with sintilimab and SOX yielded quite high R0 conversion rate and R0 resection rate with a manageable safety profile in unresectable GC/GEJC, representing a potential and feasible conversion therapy regimen for this population. Survival data will continue to be followed up. Clinical trial information: NCT05177068 .