Efficacy and safety of albumin-bound docetaxel vs. docetaxel in patients with previously treated advanced gastric or gastroesophageal junction adenocarcinoma: A multicenter, randomized, phase II study.

333 Background: Docetaxel has demonstrated promising activity in gastric cancer, both as monotherapy and in combination with other agents. Albumin-bound docetaxel (HB1801) is a new kind of taxane and has many advantages compared with docetaxel. Previous phase I study has demonstrated that HB1801 showed preliminary efficacy in patients with gastric cancer. Methods: In this phase II study, eligible patients were aged 18-75 years with histologically confirmed gastric or gastroesophageal junction (G/GEJ) adenocarcinoma, who progressed on at least first line of combined chemotherapy of platinum and fluorouracil. Patients were randomized (1:1) to receive HB1801 (100 mg/m 2 ) or docetaxel (Taxotere, 75 mg/m 2 ) administered every 3 weeks by intravenous infusion. Stratified factors included previous treatment with immunotherapy (yes or no) and ECOG PS (0 or 1). Primary endpoint was progression free survival (PFS). Results: As of June 25, 2024, 128 patients were randomized to the HB1801 group ( n =65) or the docetaxel group ( n =63). The two groups were comparable on baseline characteristics. Overall, the median age was 59.0 (range 27-75) years, 106 (82.8%) patients had ECOG PS of 1. 76 (59.4%) patients had received previous treatment with immunotherapy. 76 (59.4%) patients had ≥ 2 metastatic sites. Median PFS was 4.0 months (95%CI 2.8-4.2) with HB1801 versus 2.7 months (95%CI 1.8-3.0) with docetaxel, HR = 0.81(95%CI 0.53, 1.21). Objective response rate and disease control rate were 21.5% (1CR and 13 PRs, 95%CI 12.3-33.5) and 56.9% (20 SDs, 95%CI 44.0-69.2) in the HB1801 group, compared with 14.3% (1 CR and 8 PRs, 95%CI 6.8-25.4) and 42.9% (17 SDs, 95%CI 30.5-56.0) in the docetaxel group. Median overall survival was 11.3 months with HB1801 versus 7.8 months with docetaxel (HR = 0.59 [95%CI 0.35, 1.01], p=0.025). Treatment-related adverse events (TRAEs) occurred in 93.8% of patients receiving HB1801, and 93.7% of patients receiving docetaxel. Alopecia (46.2% vs. 39.7%), fatigue (43.1% vs 23.8%), anemia (40.0% vs 39.7%), hypoalbuminemia (29.2% vs 12.7%), decreased appetite (21.5% vs 12.7%), peripheral edema (16.9% vs 12.7%) and nausea (15.4% vs 19.0%) were the most common TRAEs in the HB1801 group and the docetaxel group. 20 patients (30.8%) in the HB1801 group and 19 patients (30.2%) in the docetaxel group experienced ≥grade 3 TRAEs, with the most common being anemia and fatigue. 3 patients in the docetaxel group experienced treatment emergent adverse events (TEAEs) leading to death, which one was considered to be treatment-related. No patients in the HB1801 group had TEAEs leading to death. No new safety signal was observed in HB1801 group. Conclusions: Compared with Taxotere, HB1801 results in 41% reduction in risk of death with a manageable safety profile in patients with previously treated advanced G/GEJ cancer. Clinical trial information: NCT05705635 .