Clinical trial NCT06075810: A Study of Oral MBQ-167 in Participants With Advanced Breast Cancer
Official title: A Phase 1 Open-Label, First-in-Human Trial of Oral MBQ-167 as Single Agent in Participants With Advanced Breast Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Breast Cancer
Breast Neoplasm
Breast Cancer Stage IV
Keywords: Advanced Breast Cancer
Metastatic Breast Cancer
Recurrent Breast Cancer
Lead sponsor: MBQ Pharma
Sponsor class: INDUSTRY
Collaborators: name: Congressionally Directed Medical Research Programs
First posted: 2023-10-10
Enrollment: 48
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Intervention model description: Open-label dose escalation following a standard 3+3 cohort design with a 21 day Dose Limiting Toxicity (DLT) evaluation
Primary purpose: TREATMENT

Brief summary: A Phase 1, open-label, dose-escalation clinical trial of MBQ-167 in participants with advanced Breast Cancer for whom Standard of Care (SOC) has failed or has proven intolerable.

Detailed description: The main questions this clinical trial aims to answer are:

* What, if any, are the side effects of different dose levels in humans?
* What is the maximum tolerated dose?
* How does the human body process the drug?
* Does the drug slow, stop or eliminate cancer in human participants?

Participants will be asked to:

* provide informed consent
* be evaluated by physicians and provide laboratory specimens to determine if eligible
* take MBQ-167 orally twice a day for at least 21 days
* may continue dosing, if safe to do so, until not effective or other decision to stop is made
* participate in multiple visits that include additional evaluations, laboratory tests and diary review until after stopping the investigational drug

Eligibility criteria: Key Inclusion Criteria:

* The investigator will evaluate these and other criteria to determine whether a participant can be included in this study.
* Histologically and/or cytologically confirmed advanced breast cancer which has progressed after treatment with approved therapies or for which there are no standard therapies available.
* Participants with known brain metastases may be eligible if specific conditions are met.
* Life expectancy ≥6 months, in the opinion of the investigator, after starting MBQ-167.
* Are able to swallow capsules twice daily with a meal.

Key Exclusion Criteria:

* The investigator will evaluate these and other criteria to determine whether a participant should be excluded from this study.
* Inability to take oral medication, or malabsorption syndrome or any other uncontrolled gastrointestinal condition (e.g., nausea, diarrhea, or vomiting) that might impair the bioavailability of MBQ-167.
* Females who are pregnant or breastfeeding.
* Participants who have received any anticancer treatment within 4 weeks or any investigational agent within 28 days prior to the first dose of trial drug or who have not recovered from any acute toxicity greater than Grade 0 or 1 related to previous anticancer treatment.
* Participants who have received any anticancer treatment within 4 weeks or any investigational agent within 28 days prior to the first dose of trial drug or who have not recovered from any acute toxicity greater than Grade 0 or 1 related to previous anticancer treatment.
* Active malignancies other than advanced breast cancer will be excluded from the study.

Primary outcomes:
measure: Maximum Tolerated Dose (MTD)
timeFrame: 21 days
Secondary outcomes:
measure: MBQ-167 PK parameter (Cmax/min)
timeFrame: 56 days
measure: MBQ-167 PK parameter (tmax)
timeFrame: 56 days
measure: MBQ-167 PK parameter (t1/2)
timeFrame: 56 days
measure: MBQ-167 PK parameter (AUC (0-t,0-24,∞))
timeFrame: 56 days
measure: MBQ-167 PD parameter (differential gene expression)
timeFrame: 16 days
measure: MBQ-167 PK/PD parameter (minimum dose for therapeutic response)
timeFrame: 56 days
Other outcomes:
Locations:
city: Beverly Hills
country: United States
facility: Precision Next Gen Oncology & Research Center
state: California
city: Sarasota
country: United States
facility: Florida Cancer Specialists / Sarah Cannon Research Institute / SCRI
state: Florida
city: Nashville
country: United States
facility: Sarah Cannon Research Institute/SCRI
state: Tennessee
city: San Juan
country: Puerto Rico
facility: FDI Clinical Research
Study officials:
affiliation: CMO, MBQ Pharma
name: Neil Sankar, MD
role: STUDY_DIRECTOR
References:
citation: Cruz-Collazo A, Ruiz-Calderon JF, Picon H, Borrero-Garcia LD, Lopez I, Castillo-Pichardo L, Del Mar Maldonado M, Duconge J, Medina JI, Bayro MJ, Hernandez-O'Farrill E, Vlaar CP, Dharmawardhane S. Efficacy of Rac and Cdc42 Inhibitor MBQ-167 in Triple-negative Breast Cancer. Mol Cancer Ther. 2021 Dec;20(12):2420-2432. doi: 10.1158/1535-7163.MCT-21-0348. Epub 2021 Oct 4.
citation: Medina JI, Cruz-Collazo A, Del Mar Maldonado M, Gascot TM, Borrero-Garcia LD, Cooke M, Kazanietz MG, O'Farril EH, Vlaar CP, Dharmawardhane S. Characterization of Novel Derivatives of MBQ-167, an inhibitor of the GTP-binding proteins Rac/Cdc42. Cancer Res Commun. 2022 Dec;2(12):1711-1726. doi: 10.1158/2767-9764.crc-22-0303. Epub 2022 Dec 29.
citation: Humphries-Bickley T, Castillo-Pichardo L, Hernandez-O'Farrill E, Borrero-Garcia LD, Forestier-Roman I, Gerena Y, Blanco M, Rivera-Robles MJ, Rodriguez-Medina JR, Cubano LA, Vlaar CP, Dharmawardhane S. Characterization of a Dual Rac/Cdc42 Inhibitor MBQ-167 in Metastatic Cancer. Mol Cancer Ther. 2017 May;16(5):805-818. doi: 10.1158/1535-7163.MCT-16-0442.
citation: Torres-Sanchez A, Rivera-Robles M, Castillo-Pichardo L, Martinez-Ferrer M, Dorta-Estremera SM, Dharmawardhane S. Rac and Cdc42 inhibitors reduce macrophage function in breast cancer preclinical models. Front Oncol. 2023 Jun 16;13:1152458. doi: 10.3389/fonc.2023.1152458. eCollection 2023.
citation: Maldonado MDM, Dharmawardhane S. Targeting Rac and Cdc42 GTPases in Cancer. Cancer Res. 2018 Jun 15;78(12):3101-3111. doi: 10.1158/0008-5472.CAN-18-0619. Epub 2018 Jun 1.
citation: Borrero-Garcia LD, Del Mar Maldonado M, Medina-Velazquez J, Troche-Torres AL, Velazquez L, Grafals-Ruiz N, Dharmawardhane S. Rac inhibition as a novel therapeutic strategy for EGFR/HER2 targeted therapy resistant breast cancer. BMC Cancer. 2021 Jun 1;21(1):652. doi: 10.1186/s12885-021-08366-7.