Sintilimab plus oxaliplatin and capecitabine versus sintilimab plus albumin-bound paclitaxel and capecitabine for advanced unresectable gastric and gastroesophageal junction (GEJ) adenocarcinoma patients: A prospective, randomized, open-label, investigator-initiated phase 2 trial.

Abstract

e16042 Background: The treatment options for locally advanced unresectable GEJ adenocarcinoma are still limited in China. Sintilimab is a PD1 mAb, previous ORIENT-16 study has demonstrated its combination with XELOX regimen had improved OS and tolerable toxicity in first line GEJ carcinoma treatment. Nanoparticle albumin-bound paclitaxel is a form of paclitaxel that does not require steroid premedication to prevent hypersensitivity reactions, which may bring more benefits for this cohort of patients. Methods: Patients with pathologically confirmed advanced unresectable GEJ adenocarcinoma were enrolled and randomly assigned to arm A: sintilimab 200mg, IV, D1, Q3W; capecitabine 1000 mg/m 2 , PO, BID, D1-14, Q3W; oxaliplatin 130 mg/m 2 , IV, Q3W; and arm B: albumin-bound paclitaxel 260 mg/m 2 , IV, D1, Q3W, sintilimab and capecitabine dose were the same with arm A. The primary endpoints were ORR and PFS per RECIST 1.1. Results: As of 28 th Dec 2024, 39 patients were enrolled, 23 from arm A and 16 from arm B. In these 2 arms, median age were 69 and 70, male patients accounted for 60.9% and 87.5%, respectively; in arm A, 78.3% subjects had ECOG score 0, 21.7% had score 1, in arm B, they were both 50%; 8.7% subjects in arm A had > = 3 metastatic sites, and that in arm B was 6.3%. 23 arm A and 16 arm B patients were analyzed for safety profile, 39.1% of patients in arm A had any grade treatment-emergent adverse events (TEAEs), the most common (> 10%) was anemia (21.7%),; 43.8% in arm B had any-grade TEAEs, with the most common being hepatic failure (12.5%). 17.4% of patients in arm A had dose interruption/delay, and 17.4% had dose reduction, those in arm B were 18.8% and 0. Immune-related AEs occurred in 4.3% of patients in arm A (hepatic failure) and none in arm B. Efficacy was analyed in 20 patients from arm A and 16 from arm B, the confirmed ORR was 35.0% (7/20, 95% CI 15.4%- 59.2%) and 37.5% (6/16, 95% CI 15.2%- 64.6%), respectively. Disease control rate (DCR) was 85.0% (17/20, 95% CI 62.1%-96.8%) and 93.8% (15/16, 95% CI 69.8%-99.8%), respectively, and the median PFS was 6.74 months (95% CI 4.73-Not reached) in arm A and 7.23 months (95% CI 7.23-Not reached) in arm B. Conclusions: Sintilimab in combination with albumin-bound paclitaxel and capecitabine showed similar efficacy with sintilimab plus XELOX, with tolerable toxicity, however, due to limited sample size and follow-up time, it’s hard to draw any solid conclusions, we will continue to observe the safety and efficacy of this regimen in locally advanced unresectable gastric and gastroesophageal adenocarcinoma patients. Clinical trial information: ChiCTR2300077373 .