A phase 1b/2 study on the efficacy and safety of BXQ-350, a first-in-class sphingolipid metabolism modulator, in combination with mFOLFOX7 and bevacizumab in newly diagnosed metastatic colorectal carcinoma

Tariq Arshad; Michael Gazda; Gilles Tapolsky; Jim Beach; Daniel Blake Flora; Reema Anil Patel; Fa Chyi Lee; Douglas B. Flora; Davendra Sohal; Saima Sharif; Ki Young Chung; John L. Villano; Vivek Sharma; Julie Anne L. Gemmill; Agustin Pimentel; Nashat Y. Gabrail; Darryl Alan Outlaw; Ari David Baron; Brian C. Boulmay; Bexion Pharmaceuticals

doi:10.1200/JCO.2026.44.2_suppl.TPS273

Back

A phase 1b/2 study on the efficacy and safety of BXQ-350, a first-in-class sphingolipid metabolism modulator, in combination with mFOLFOX7 and bevacizumab in newly diagnosed metastatic colorectal carcinoma

Abstract

Peer reviewed

A phase 1b/2 study on the efficacy and safety of BXQ-350, a first-in-class sphingolipid metabolism modulator, in combination with mFOLFOX7 and bevacizumab in newly diagnosed metastatic colorectal carcinoma

Tariq Arshad, Michael Gazda, Gilles Tapolsky, Jim Beach, Daniel Blake Flora, Reema Anil Patel, Fa Chyi Lee, Douglas B. Flora, Davendra Sohal, Saima Sharif, …

Journal of clinical oncology, Vol.44(2_suppl)

01/10/2026

DOI: 10.1200/JCO.2026.44.2_suppl.TPS273

View Online

Abstract

TPS273 Background: Ceramides and sphingosine-1-phosphate (S1P) are key bioactive signaling molecules. Ceramides are proapoptotic and mitigate chemoresistance. Conversely, S1P promotes cancer cell proliferation, activates multiple oncogenic pathways, and stimulates immuno-suppressor cell populations promoting a pro-tumoral microenvironment. 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. Hence, modulation of sphingolipid metabolism could be a promising therapeutic approach. BXQ-350 is a nanovesicle of Saposin C, an allosteric activator of sphingolipid metabolism, that lowers systemic S1P and increases C18 ceramide. BXQ-350 was investigated in a Phase 1 dose-escalation safety study in cancer 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 the Phase 1b (open label study): A safety dose escalation part to establish the RP2D: patients will initially receive 1.8 mg/kg BXQ-350 in combination with mFOLFOX7 and Bevacizumab. If safe (no MTD), dose of BXQ-350 will be increased to 2.4 mg/kg and 9 additional patients will be entered at this dose level. If safe, then this dose will be the RP2D and 21 additional patients will be enrolled, completing a 30-patient expansion cohort. Efficacy will then be evaluated for all patients entered at the RP2D. Primary objectives of the Phase 1b are to assess safety, identify RP2D, and assess preliminary efficacy of BXQ-350 in this combination. A secondary objective is to determine if BXQ-350 decreases CIPN. Design of the Phase 2, a double-blinded, placebo-controlled study: Eligible patients (up to 160 patients) will be randomized in a 1:1 fashion to receive either BXQ-350 or placebo with mFOLFOX7 + Bevacizumab. Primary and secondary objectives include efficacy, safety and CIPN incidence. Enrollment in the Phase 1b dose escalation portion is completed. After review of the safety results, the DSMB approved enrollment of the expansion cohort, with a planned 30 patients at the Phase 2 dose. Primary endpoints are Cumulative Oxaliplatin Dose, ORR and Safety. Secondary endpoints are OS, PFS, DCR, CIPN, PK/PD and biomarkers. Clinical trial information: NCT05322590 .

Details

Title: Subtitle: A phase 1b/2 study on the efficacy and safety of BXQ-350, a first-in-class sphingolipid metabolism modulator, in combination with mFOLFOX7 and bevacizumab in newly diagnosed metastatic colorectal carcinoma
Creators: Tariq Arshad - Bexion Pharmaceuticals (United States)
Michael Gazda - Bexion Pharmaceuticals (United States)
Gilles Tapolsky - Bexion Pharmaceuticals (United States)
Jim Beach - Bexion Pharmaceuticals (United States)
Daniel Blake Flora - St. Elizabeth Healthcare
Reema Anil Patel - University of Kentucky
Fa Chyi Lee - University of California, Irvine
Douglas B. Flora - St. Elizabeth Healthcare
Davendra Sohal - University of Cincinnati
Saima Sharif - University of Iowa
Ki Young Chung
John L. Villano - University of Kentucky
Vivek Sharma - James Graham Brown Foundation
Julie Anne L. Gemmill - Stony Brook University Hospital
Agustin Pimentel - University of Miami
Nashat Y. Gabrail - Gabrail Cancer Center
Darryl Alan Outlaw - University of Alabama at Birmingham
Ari David Baron - Hematology Oncology Associates
Brian C. Boulmay - Louisiana State University Health Sciences Center New Orleans
Bexion Pharmaceuticals
Resource Type: Abstract
Publication Details: Journal of clinical oncology, Vol.44(2_suppl)
DOI: 10.1200/JCO.2026.44.2_suppl.TPS273
ISSN: 0732-183X
eISSN: 1527-7755
Publisher: LIPPINCOTT WILLIAMS & WILKINS; PHILADELPHIA
Grant note: Bexion Pharmaceuticals
Bexion Pharmaceuticals
Language: English
Date published: 01/10/2026
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
Record Identifier: 9985121498802771

Metrics

3 Record Views