Efficacy and safety results of a multi-center phase II study of utidelone injection in combination with PD-1 inhibitor and chemotherapy for the first-line treatment of advanced gastric and esophagus cancers.

Abstract

4040 Background: Utidelone is a novel microtubule inhibitor that offers several advantages including improved efficacy and safety, broader anti-cancer spectrum, blood-brain barrier penetrance, and response against multidrug-resistant tumors. Utidelone injection (UTD1) has been approved for advanced breast cancer in China. Previous studies have shown that utidelone monotherapy is effective for advanced gastric and gastroesophageal junction adenocarcinoma (GC) and esophageal squamous cell carcinoma (ESCC). This phase II study further explored the efficacy and safety of utidelone in combination with PD-1 inhibitor and chemotherapy for the 1 st line treatment of advanced GC and ESCC. Methods: Eligible patients were recruited into the two cohorts of metastatic and/or unresectable HER2 negative GC or ESCC, receiving utidelone (30mg/m 2 /day iv on days 1–5 every 21-day) plus sintilimab (200 mg iv Q3W) and oxaliplatin (130 mg/m 2 /day Q3W for up to 6 cycles), or utidelone (30mg/m 2 /day iv on days 1–5 every 21-day) plus tislelizumab (200 mg iv Q3W) and capecitabine (2000mg/m 2 /day po on days 1–14 every 21-day), respectively, until disease progression or unacceptable toxicity. The primary endpoint is ORR and second endpoints are CBR, PFS and safety. Results: The enrolment has been completed for both cohorts from April 2023 to October 2024. There were 27 eligible patients enrolled in the GC cohort with median age of 60 years (range 34-70), 6 females and 21 males. 23 patients were evaluable for efficacy with an outcome of 11 confirmed PRs and 12 SDs including 4 unconfirmed PR, and 5 patients were still receiving treatment (1-23 cycles). The confirmed ORR was 47.8% and CBR was 100%. The mPFS was > 5.3 months. The most common ≥Grade 3 TEAEs included diarrhea (25.93%), neutropenia (14.81%), vomiting (14.81%), peripheral sensory neuropathy (11.11%), anemia (11.11%) and leukopenia (11.11%). Other AEs were all Grade 1 or 2, with no treatment-related deaths. There were 20 eligible patients enrolled in the ESCC cohort with median age of 61.5 years (range 47-70), 5 females and 15 males. 18 patients were evaluable for efficacy with an outcome of 6 confirmed PRs and 12 SDs, and 6 patients were still receiving treatments (1-12 cycles). The confirmed ORR was 33.3% and CBR was 100%. TEAEs ≥Grade 3 occurred in 8 patients including hypokalemia, lymphopenia/leukopenia, peripheral sensory neuropathy, hiccup, rash, pain, hypotension and anemia with one occurrence for each (5.5%). Other AEs were all Grade 1 or 2, with no treatment-related deaths. Conclusions: Utidelone plus PD-1 inhibitor and chemotherapy demonstrated promising efficacy and acceptable safety as first-line treatment for advanced GC and ESCC. There are 11 patients still on the study receiving continuous treatment. The final data will be provided at the time of presentation. Clinical trial information: NCT04911907 .