PD-1 inhibitor (sintilimab) and fruquintinib plus SOX as conversion therapy for initially unresectable gastric/gastroesophageal junction adenocarcinoma (GC/GEJC): Updated results from a single-arm, phase 2 clinical trial.

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406 Background: The evidence of conversion therapy for unresectable GC/GEJC is limited. Previously, preliminary results of the ongoing open-label, phase 2 study (NCT05177068) have showed promising R0 surgical conversion rate (62.1%), R0 resection rate (100%) and acceptable tolerability in unresectable GC/GEJC with sintilimab and fruquintinib plus SOX (ASCO 2024). Here we present updated results with longer follow-up duration, including more enrolled patients. Methods: Eligible patients 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. Patients 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 July 30, 2024, 42 pts (37 males/5 females) with a median age of 64 years (range: 43–76), 71% ECOG PS1, 55% GEJC were enrolled. 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), liver metastasis 11.9% (5), peritoneal metastasis 4.8% (2), para-aortic lymph node metastasis 2.4% (1), and local progression 38.1% (16). Of 35 evaluable pts, ORR was 68.6% and DCR was 97.1%. Among the 29 pts who had completed surgical conversion, the R0 resection rate was 100% (29/29) and R0 surgical conversion rate was 82.9% (29/35). 10.3% (3/29) pts achieved pathological complete response (pCR), and 20.7% (6/29) pts reached tumor regression grade (TRG) 0-1. Additionally, the pathological response rate (pRR) according to JCGC (≥ Grade 1b) was 93.1% (27/29). Seven pts (16.7%) had grade 3 treatment-emergent adverse events, 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 severe surgery-related complication was observed. Conclusions: Fruquintinib combined with sintilimab and SOX yielded very 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 .

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