Conversion effects of PD-1 inhibitor camrelizumab (Cam) combined with Nab-POF regimen in patients (pts) with initially unresectable locally advanced or limited metastatic gastric or gastroesophageal junction adenocarcinoma: FDZL-001 trial.

Abstract

334 Background: For initially unresectable locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma, the prognosis is poor and chemotherapy is the main treatment option. The AIO-FLOT3 Trial suggested that conversion therapy might improve outcome in pts with limited metastatic gastric cancer (GC). We conducted this prospective, single-arm, phase II trial to improve conversion efficacy of PD-1 inhibitor Cam combined with Nab-POF regimen (nab-paclitaxel , oxaliplatin, fluorouracil) in pts with initially unresectable locally advanced or limited metastatic gastric or gastroesophageal junction adenocarcinoma. Methods: Eligible pts received Cam 200mg, nab-PTX 125 mg/m 2 , oxaliplatin 85 mg/m 2 or with trastuzumab if Her2 positive, each was an IV followed by fluorouracil 2400 mg/m 2 as a 48-h continuous IV on day 1, every 2 weeks. Patients were assessed for tumor response and surgical feasibility every 3 cycles, and if confirmed feasible for surgical resection by both surgical and medical experts after 6 cycles, they would undergo surgery within 3-6 weeks. The primary endpoint was R0 resection rate. Results: In total, 53 pts were enrolled up to 01/2024. 52 pts were evaluable. 50% are younger than 65 years of age. Male was 73.1%. The metastatic sites included liver 46.2% (24), retroperitoneal lymph nodes 40.4% (21), Krukenberg 5.8% (3), and locally advanced unresectable tumors 21.2% (11). 4 pts (7.7%) were dMMR/MSI-H and 10 (19.2%) were Her2 positive. ORR was 88.5% (46/52) and DCR was 98.1% (51/52). 45(86.5%) pts were assessed as resectable. 3 pts (6.8%) refused surgery and 3 (6.8%) were cCR under observation. The R0 resection rate was 75.0% (39/52). CR rate was 23.1% (cCR, 5.8%; pCR,17.3%). The mPFS was not reached (95% CI = 17.0-NE), and the mOS was not reached (95% CI = 25.4-NE), either. The 3-year PFS and OS rate were 56.9% (95% CI = 45.7%-86.3%) and 62.8% (95% CI = 41.6%-78.0%), respectively. The 3 cCR pts have survived utill the last follow-up date of 07/2025 without tumors for 17, 29, and 34 months, respectively. Pts tolerated treatment well, although all pts experienced treatment-related adverse events (AE). Grade 3/4 AEs were 42.3% (22/52) and neutrophil decrease was the most common at 36.5%. 10 patients (19.2%) experienced immune related AEs (irAEs), and 2 of them experienced grade 3 irAEs. Conclusions: The PD-1 inhibitor Cam combined with the Nab-POF regimen safely induced a high conversion rate with very high R0 resection and high 3-year PFS and OS rates, preliminarily demonstrating promising effects, providing a new conversion drug treatment option for pts with initially unresectable locally advanced or limited metastatic advanced GC. These findings warrant further prospective, randomized controlled investigations. Clinical trial information: NCT04510064 .