A Study of Oral MBQ-167 in Participants With Advanced Breast Cancer

Breast Cancer Clinical Trial

Official title:

A Phase 1 Open-Label, First-in-Human Trial of Oral MBQ-167 as Single Agent in Participants With Advanced Breast Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06075810
• Other study ID #: MBQ-ABC001
• Secondary ID: CDMRP-BC220292
• Status: Recruiting
• Phase: Phase 1
• Start date: November 9, 2023
• Est. completion date: October 31, 2024

Study information

• Verified date: November 2023
• Source: MBQ Pharma
• Contact: Scott Houston
• Phone: (415) 404 8838
• Email: scott.houston[@]mbqpharma.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 48
• Est. completion date: October 31, 2024
• Est. primary completion date: October 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years and older

Eligibility

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.

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 30 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 30 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.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Cancer Stage IV
• Breast Neoplasm
• Breast Neoplasms

Intervention

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

Locations

Country	Name	City	State
Puerto Rico	FDI Clinical Research	San Juan

Sponsors (2)

Lead Sponsor	Collaborator
MBQ Pharma	Congressionally Directed Medical Research Programs

Country where clinical trial is conducted

Puerto Rico, 

References & Publications (6)

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. — View 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. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Tolerated Dose (MTD)	To find the maximum tolerated dose (MTD) of MBQ-167 as a single agent administered orally, BID continuously for 21 days in participants with Advanced Breast Cancer (ABC) by evaluating for the presence or absence of dose-limiting toxicity (DLT) related to MBQ-167 administered in cohorts of participants at escalating sequential cohort dose levels.	21 days
Secondary	MBQ-167 PK parameter (Cmax/min)	Maximum and minimum observed plasma concentration at steady state	56 days
Secondary	MBQ-167 PK parameter (tmax)	Time to maximum plasma concentration	56 days
Secondary	MBQ-167 PK parameter (t1/2)	Terminal elimination half-life	56 days
Secondary	MBQ-167 PK parameter (AUC (0-t,0-24,8))	Area under the concentration-time curve over the dosing interval time from time 0	56 days
Secondary	MBQ-167 PD parameter (differential gene expression)	Observed quantitative measurement of gene expression change from baseline	16 days
Secondary	MBQ-167 PK/PD parameter (minimum dose for therapeutic response)	Correlate differential gene expression change, objective response and PK parameter Cmax/min to identify a minimum dose for therapeutic response	56 days