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

Overview

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

Interventions

• Drug MBQ-167
  MBQ-167, an inhibitor of Rho GTPases Rac and Cdc42

Primary outcome measures

• Maximum Tolerated Dose (MTD) [Time frame: 21 days]

Secondary outcome measures (6)

• MBQ-167 PK parameter (Cmax/min) [Time frame: 56 days]
• MBQ-167 PK parameter (tmax) [Time frame: 56 days]
• MBQ-167 PK parameter (t1/2) [Time frame: 56 days]
• MBQ-167 PK parameter (AUC (0-t,0-24,∞)) [Time frame: 56 days]
• MBQ-167 PD parameter (differential gene expression) [Time frame: 16 days]
• MBQ-167 PK/PD parameter (minimum dose for therapeutic response) [Time frame: 56 days]

Eligibility criteria

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.

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 3 centers

• Precision Next Gen Oncology & Research Center — Beverly Hills
• Florida Cancer Specialists / Sarah Cannon Research Institute / SCRI — Sarasota
• Sarah Cannon Research Institute/SCRI — Nashville

Puerto Rico · 1 center

• FDI Clinical Research — San Juan

Publications

• 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. PMID 34607932
• 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. PMID 36861094
• 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. PMID 28450422
• 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. PMID 37397366
• 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. PMID 29858187
• 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. PMID 34074257

Identifiers

NCT: NCT06075810 · MBQ-ABC001 · CDMRP-BC220292

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗