OncoVee™-MiniPDX-guided anticancer treatment for HER2-negative intermediate-advanced gastric cancer patients: a single-arm, open-label phase I clinical study

Abstract

BackgroundChemotherapy is the main treatment strategy for patients with advanced HER2-negative gastric cancer (GC); yet, many patients do not respond well to treatment. This study evaluated the sensitivity of a mini patient-derived xenograft (MiniPDX) animal model in patients with HER2-negative intermediate-advanced GC.MethodsIn this single-arm, open-label clinical study, we consecutively recruited patients with HER2-negative advanced or recurrent GC from September 2018 to July 2021. Tumor tissues were subjected to MiniPDX drug sensitivity tests for screening individualized anti-tumor drugs; appropriate drug types or combinations were selected based on drug screening results. The primary endpoints were progression-free survival (PFS) and safety, and the secondary endpoints were overall survival (OS) and objective response rate (ORR).ResultsA total of 17 patients were screened, and 14 eligible patients were included.The median follow-up time was 9 (2–34) months. The median PFS time was 14.1 (2–34) months, the median OS time was 16.9 (2–34) months, ORR was 42.9% (6/14), and DCR was 92.9% (13/14). The most common treatment-related adverse events (TRAE) were fatigue (14 (100%)), anorexia (13 (93%)) and insomnia (12 (86%)), and the most common grade 3 or worse TRAE was fatigue (6 (43%)), and anorexia (6 (43%)). The occurrence rate of myelosuppression, nausea and vomiting, abnormal liver enzymes, and other grade 3–4 chemotherapy adverse reactions were relatively low, and no grade 5 treatment-related adverse events occurred.ConclusionScreening HER2-negative medium-advanced GC/GJC chemotherapy regimens and targeted drugs based on MiniPDX animal models showed good tumor activity and safety.