A phase 1, safety and dose escalation study of BXQ-350, a nanovesicle formulation of saposin c, a modulator of sphingolipid metabolism, in patients with advanced solid malignancies.

e15059 Background: Bexion recently completed an all-comer Phase 1 clinical study of BXQ-350 in patients with advanced solid tumors including high grade gliomas to evaluate the safety profile and to determine the maximum tolerated- or biologically effective dose. BXQ-350 is a nanovesicle comprised of recombinantly expressed Saposin C (SapC) and dioleoylphosphatidylserine. SapC, a human protein encoded by the Psap gene, is an allosteric activator of several enzymes involved sphingolipid metabolism. Sphingolipids are bioactive signaling molecules implicated in multiple cellular processes including apoptosis and immune stimulation/inhibition. In nonclinical studies, BXQ-350 evidences broad anticancer activity, selectively inducing apoptosis of cancer cells by modulating sphingolipids (ceramides/S1P), and BXQ-350 acts synergistically with multiple classes of anticancer agents and treatments. Methods: In the trial (NTC02859857), performed at four US sites, BXQ-350 was administered intravenously for a minimum of 6 cycles over 28 weeks at escalating doses from 0.7 mg/kg up to 2.4 mg/kg. Multiple secondary parameters were included to characterize its pharmacokinetics, efficacy profile and identify potential biomarkers. Results: Results indicate that: i) BXQ-350 was safe and well-tolerated as no DLT was observed and an MTD was not reached; ii) treatment related adverse events leading to discontinuation were typical for this patient population and disease related; iii)* biomarker analyses suggest positive modulation of sphingolipid metabolism and stimulation of the immune system; iv)* surprisingly, some patients noted improvement of existing peripheral neuropathies. RANO or RECIST ver 1.1 criteria were used to evaluate tumor response: 13 patients reached Cycle 6 restaging (17% ORR); 8 patients (11.0% of evaluable patients) demonstrated progression free survival over more than 6 months; and 2 patients (a GBM and CRC patient) are still on study after 5 years. * subject of separate abstracts. Conclusions: In conclusion, BXQ-350 is a first-in-human and first-in-class novel biologic whose Phase 1 results suggest that it may have clinical utility either as a monotherapy or when combined with other targeted agents. Clinical trial information: 028559857.