BXQ-350 efficacy and safety evaluation in first line mCRC patients: A phase 1b/2 study of BXQ-350, a first-in-class sphingolipid metabolism modulator, in combination with mFOLFOX7 plus bevacizumab in newly diagnosed metastatic colorectal carcinoma.

242 Background: BXQ-350 is a first-in-class biologic nanovesicle of Saposin C, an allosteric activator of sphingolipid metabolism, that lowers systemic S1P and increases C18 ceramide. Several studies in colorectal cancer patients have shown high levels of ceramides are associated with improved survival, while high S1P levels are associated with a poor prognosis. BXQ-350 was investigated in a Phase 1 dose-escalation safety study in patients with advanced solid malignancies (NCT02859857). BXQ-350 was safe and well-tolerated (no DLT, no MTD). Methods: BXQ-350 is being investigated in a Phase 1b/2 study in combination with mFOLFOX7 and Bevacizumab in newly diagnosed mCRC patients (NCT05322590) to assess the efficacy and safety of BXQ-350. Design of Phase 1b/2 open label study: Safety dose escalation to establish RP2D: patients initially receive 1.8 mg/kg BXQ-350 in combination with mFOLFOX7 and Bevacizumab. If safe (no MTD), dose of BXQ-350 increased to 2.4 mg/kg and 9 additional patients entered at this dose level. If safe, then this dose is RP2D and 21 additional patients enrolled, completing 30-patient expansion cohort. Efficacy evaluated for all patients entered at RP2D. Primary objectives of Phase 1b/2 are to assess safety, identify RP2D, and assess preliminary efficacy of BXQ-350 in this combination. Secondary objective is to determine if BXQ-350 decreases CIPN. Results: Total of 34 evaluable patients were enrolled in the Phase 1b/2 trial. 32 patients have completed primary treatment period (6 months of SoC treatment plus BXQ-350). 5 patients are currently still receiving BXQ-350 in the Extended Treatment period. BXQ-350 combined with SoC in this population showed the following results: 94% patients reached 8 Cycles or more of Oxaliplatin without Oxaliplatin being halted due to CIPN; Improvements in Cumulative Oxaliplatin Dose (COD) and Relative Dose Intensity (RDI) with reduced dose vacations compared to natural history of Oxaliplatin in this population; Decreased intensity of CIPN with reduced incidence of Grade 2 or above CIPN and delayed time of CIPN onset; and DCR, ORR and mPFS compare favorably to natural history of Oxaliplatin in this population Conclusions: BXQ-350 was safe and well tolerated in combination with SoC. Ongoing monitoring of patients suggests BXQ-350 when added to SoC may provide additional clinical benefits in this population as compared to natural history of these patients, both in terms of increasing COD & RDI as well as amelioration of CIPN. Clinical trial information: NCT05322590 .