The study will assess the safety and efficacy of BXQ-350 plus modified FOLFOX7 (mFOLFOX7) and bevacizumab in participants who have newly diagnosed metastatic adenocarcinoma of the colon/rectum. The study will also evaluate if the administration of BXQ-350 with mFOLFOX7 and bevacizumab may diminish oxaliplatin induced sensory neurotoxicity, enabling participants to receive the total and planned doses of mFOLFOX7. All participants will receive BXQ-350 by intravenous (IV) infusion along with standard of care doses of mFOLFOX and bevacizumab. The study is divided into two stages: Stage 1 will be open label and will enroll participants at increasing dose levels of BXQ-350 in order to determine the Stage 2 dose. Stage 2 will be blinded; participants will receive BXQ-350 at the established Stage 1 dose or placebo.
BXQ-350 is a novel anti-neoplastic therapeutic agent configured from two components: Saposin C (SapC), an expressed (human) lysosomal protein, and the phospholipid dioleoylphosphatidyl-serine (DOPS), a cell membrane phospholipid (clinical formulation BXQ-350).Due to the presumed mechanism of action of BXQ-350, Bexion anticipates that it may have an impact on ceramides, sphingosine-1-phosphate (S1P), and inflammatory cytokine levels. In addition, pre-clinical results demonstrated that BXQ-350 induced neurite generation and protection in vitro in the PC-12 and NS20Y cell lines and significantly decreased oxaliplatin-induced cold allodynia in a model of CIPN. Thus BXQ-350 may represent a new approach to deliver a neuropathy benefit. The unique combination of BXQ-350 along with its proven safety profile, potential efficacy, and possible neuropathy benefit makes BXQ-350 a worthwhile candidate to use in combination with standard of care treatment for mCRC to not only enhance the standard treatment of mCRC, but also to evaluate its ability to alleviate side effects related to oxaliplatin-induced sensory neurotoxicity.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
195
BXQ-350 is a novel anti-neoplastic therapeutic agent configured from two components: Saposin C (SapC), an expressed (human) lysosomal protein, and the phospholipid dioleoylphosphatidyl-serine (DOPS), a phospholipid located on cell membranes (clinical formulation BXQ-350). BXQ-350 will be administered by intravenous (IV) infusion over six months and continued for an additional 20 months for participants who remain eligible.
Placebo will be 0.9% normal saline of matching volume to BXQ-350 administered by intravenous (IV) infusion over six months and continued for an additional 20 months for participants who remain eligible (Stage 2 only)
University of Alabama at Birmingham
Birmingham, Alabama, United States
UC Irvine Health
Orange, California, United States
Pacific Hematology Oncology Associates
San Francisco, California, United States
Sylvester Comprehensive Cancer Center, University of Miami Hospitals and Clinics
Miami, Florida, United States
The University of Iowa Hospitals and Clinics
Iowa City, Iowa, United States
St. Elizabeth Healthcare
Edgewood, Kentucky, United States
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, United States
University of Louisville, James Graham Brown Cancer Center
Louisville, Kentucky, United States
University Medical Center New Orleans
New Orleans, Louisiana, United States
Stony Brook Cancer Center
Stony Brook, New York, United States
...and 2 more locations
Recommended Phase 2 Dose
To determine the recommended phase 2 dose of BXQ-350, when given with mFOLFOX7 and bevacizumab, according to the investigational product (IP) related dose limiting toxicities (DLTs).
Time frame: 6 months
Incidence of Treatment Emergent Adverse Events as Assessed by CTCAE v5.0
To determine the safety of BXQ-350 when given with mFOLFOX7 and bevacizumab, as evidenced by the incidence of treatment emergent adverse events assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
Time frame: 6 months
Objective Response Rate (ORR)
To determine the ORR of BXQ-350 when given with mFOLFOX7 and bevacizumab. ORR is defined as the percentage of participants with evidence of a complete or partial response as per the Response Evaluation Criteria in Solid Tumors (RECIST).
Time frame: 6 months
Peak Plasma Concentration (Cmax)
To evaluate the Cmax of BXQ-350 in combination with mFOLFOX7 and bevacizumab.
Time frame: 6 months
Overall Survival (OS)
To evaluate OS in participants receiving BXQ-350 with mFOLFOX7 and bevacizumab. OS is defined as the time from the date of randomization until date of death due to any cause.
Time frame: 6 months
Progression Free Survival (PFS)
To evaluate PFS in participants receiving BXQ-350 with mFOLFOX7 and bevacizumab. PFS is defined as the time from the date of randomization until date of disease progression or death.
Time frame: 6 months
Duration of Response (DoR)
To evaluate DoR in participants receiving BXQ-350 with mFOLFOX7 and bevacizumab. DoR is defined as the time from documentation of disease response to disease progression according to RECIST.
Time frame: 6 months
Disease Control Rate (DCR)
To evaluate DCR in participants receiving BXQ-350 with mFOLFOX7 and bevacizumab. DCR is defined as the proportion of participants whose best overall response (BOR) was complete (CR), partial response (PR) and stable disease (SD) according to RECIST.
Time frame: 6 months
Total Sensory Neuropathy
To evaluate chronic neuropathy symptoms in participants receiving BXQ-350 with mFOLFOX7 and bevacizumab. Total sensory neuropathy scores will be obtained from the EORTC QLQ-CIPN20 questionnaire.
Time frame: 6 months
CIPN Assessment
To evaluate acute CIPN symptoms in participants receiving BXQ-350 with mFOLFOX7 and bevacizumab utilizing the CIPN Assessment Tool questionnaire.
Time frame: 6 months
Post Oxaliplatin Assessment
To evaluate acute CIPN symptoms post oxaliplatin dosing in participants receiving BXQ-350 with mFOLFOX7 and bevacizumab utilizing the Post-oxaliplatin Symptom questionnaire.
Time frame: 6 months
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