Phase II clinical trial of PLX038 in patients with platinum resistant ovarian, primary peritoneal and fallopian tube cancer.

• DOI: 10.1200/jco.2024.42.16_suppl.tps5630
• Publication Date: 2024-07-23T18:28:09Z
• Authors: Andrea Elisabeth ...; Nathan R. Foster; Tracy Clasemann; Megan Grudem; Carolyn Klampe; Matthew Stephen B...; Aminah Jatoi; Saravut John Weroha; Grace Mei Yee Choong; Siddhartha Yadav; Lynn M Flickinger; Gary W Ashley; Peter J. Langecker; Daniel V Santi; Scott H. Kaufmann
• Keywords: Fallopian tube; Fallopian tube cancer

TPS5630 Background: Platinum-resistant ovarian cancer (PROC) portends a poor prognosis and, although treatments are available, response rates low. Previous studies have demonstrated that DNA topoisomerase I (TOP1) inhibitors exhibit clinical activity in PROC. Irinotecan also has 15-25% rate some of platinum-resistant epithelial but does not FDA approval for this indication. Additional preclinical models suggest TOP1 poisons more active if administered at low doses on prolonged schedules. PLX038 is long-acting prodrug the potent inhibitor SN-38. In PLX038, SN-38 covalently conjugated to circulating polyethylene glycol and slowly released constant provide agent with long half-life, C max very high exposure – important facets optimal safety efficacy drug. Further, nanoparticle accumulates retained tumors, where it releases Methods: This single arm, phase 2 trial open Mayo Clinic Rochester, MN. The primary endpoint overall secondary endpoints include progression-free survival assessment tolerability PLX038. Correlative goals i) measurement TOP1-DNA covalent complexes tumor biopsies cells assess successful target engagement; ii) homologous recombination status SLFN11 expression correlation rate; iii) pharmacokinetics SN-38G as well their association GI toxicity. Assessment gut microbiota toxicity profile being investigated. Eligible patients women platinum resistant grade serous ovarian, peritoneal, fallopian tube who received fewer than two prior chemotherapy regimens setting. All must an ECOG performance 0, 1, or adequate bone marrow, renal, hepatic function. As January 31, 2024, 12 planned 37 enrolled. Clinical information: NCT05465941 .