A first-in-human phase 1 study of BXQ-350, a first-in-class sphingolipid metabolism regulator, in patients with advanced/recurrent solid tumors or high-grade gliomas.

Autor:	Rixe O; University of New Mexico Comprehensive Cancer Center, Albuquerque, New Mexico, United States., Villano JL; University of Kentucky, Lexington, KY, United States., Wesolowski R; Ohio State University Comprehensive Cancer Center, Columbus, OH, United States., Noonan AM; The Ohio State University, Columbus, OH, United States., Puduvalli VK; The University of Texas MD Anderson Cancer Center, Houston, TX, United States., Wise-Draper TM; University of Cincinnati, Cincinnati, OH, United States., Curry R; CTI, United States., Yilmaz E; The University of Texas MD Anderson Cancer Center, Houston, TX, United States., Cruze C; Bexion Pharmaceuticals (United States), Covington, KY, United States., Ogretmen B; Medical University of South Carolina, Charleston, SC, United States., Tapolsky G; Bexion Pharmaceuticals (United States), Covington, KY, United States., Takigiku R; Bexion Pharmaceuticals (United States), Covington, KY, United States.
Jazyk:	angličtina
Zdroj:	Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2024 Sep 12. Date of Electronic Publication: 2024 Sep 12.
DOI:	10.1158/1078-0432.CCR-24-1721
Abstrakt:	Purpose: BXQ-350, a nanovesicle formulation of Saposin C, is an allosteric sphingolipid metabolism regulator that increases pro-apoptotic ceramide and decreases oncogenic sphingosine-1-phosphate (S1P) levels. We conducted a first-in-human, phase 1 study of BXQ-350. Patients and Methods: Adults (≥18 years old) with advanced/recurrent, treatment-refractory solid tumors or high-grade gliomas received BXQ-350 intravenously in five dose cohorts (0.7-2.4 mg/kg) in a 3+3 dose-escalation and expansion design. Primary endpoints during dose escalation were dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD); primary objective in expansion parts was assessment of anti-tumor activity (RECIST v1.1/RANO criteria). Results: Eighty-six patients were enrolled. DLTs were not observed during dose escalation (n=18), and a MTD was not identified. An additional 68 patients received the 2.4 mg/kg dose. Nine patients (10%) discontinued due to adverse events (AEs). The most common treatment-related AEs were nausea (24%) and fatigue (23%). Eight patients had a progression-free survival (PFS) ≥6 months. Two of these achieved a partial response, and six had stable disease, among whom three had a reduction in ≥1 target lesion. Of those with PFS ≥6 months, seven remained on study for >12 months, five for >24 months, and after seven years, two remained on study without disease progression. Conclusions: BXQ-350 was well tolerated as monotherapy at doses up to 2.4 mg/kg. It provided some lasting clinical benefit in patients with recurrent solid malignancies across several tumor types, consistent with a decreased systemic S1P/ceramide metabolic rheostat. BXQ-350 warrants further clinical investigation alone and combined with standard-of-care for advanced solid tumors.
Databáze:	MEDLINE
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