Safety, PK, and Preliminary Efficacy of MBRC-101 in Advanced Refractory Solid Tumors

NCT06014658 | Recruiting Phase 1 FDA Drug

• 1 other identifier: MBRC-101-001
• Study Type: interventional
• Target: 130
• Locations: 1 country
• Sites: 17

Brief Summary

This is a first-in-human (FIH), open label Phase 1/1b / Phase 2 study in patients with advanced metastatic solid tumors refractory to standard treatment. Phase 1 will identify potential optimal biologically relevant doses (OBRD) and the maximum tolerated dose (MTD) of MBRC-101 at one 1 or more dosing regimens. Phase 1b will evaluate the safety and preliminary clinical activity of MBRC-101 at potential OBRDs. Phase 1 and Phase 1b will both characterize single and multiple-dose PK profiles and evaluate incidence and persistence of anti-MBRC-101 Ab. Phase 2 will evaluate the efficacy of MBRC-101 at the RP2D from Phase1b.

Conditions

Cancer

Outcome Measures

Primary Outcomes (2)

• Occurrence of treatment-emergent adverse events (TEAEs)

  TEAEs will be graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v.5.0.

  Up to 24 Months

• Occurrence of dose limiting toxicities (DLTs) during the DLT evaluation period

  The DLTs are specific adverse events and are defined as any of the following: high grade non-hematologic toxicity, or hematologic toxicity.

  21 Days

Secondary Outcomes (4)

• Objective Response Rate (ORR)

  Up to 24 Months

• Duration of Response (DOR)

  Up to 24 Months

• Progression-Free Survival (PFS)

  Up to 24 Months

• Disease Control Rate (DCR)

  Up to 24 Months

Study Arms (3)

Phase 1 Dose Escalation

EXPERIMENTAL

Drug: Antibody-Drug Conjugate

Phase 1b Expansion

EXPERIMENTAL

Drug: Antibody-Drug Conjugate

Phase 2

EXPERIMENTAL

Drug: Antibody-Drug Conjugate

Interventions

Antibody-Drug Conjugate DRUG

MBRC-101: AN ANTI-EPHA5 MONOMETHYL AURISTATIN E (MMAE) ANTIBODY DRUG CONJUGATE

Phase 1 Dose Escalation; Phase 1b Expansion; Phase 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provide written consent on an Informed Consent Form (ICF), approved by an Institutional Review Board (IRB)/Independent Ethics Committee (IEC), prior to any study-specific evaluation. Patients should have the ability to read and understand the ICF, ask for any clarifications from the study staff, and be able to comply with all planned study procedures.
• years of age or older at the time of informed consent.
• Female patients must be at least 2 years postmenopausal (defined as 2 years without menses), surgically sterile (at least 6 months prior to dosing; must be documented) or practicing effective contraception (must agree to use 2 forms of contraception, 1 of which must be a barrier method) and willing to continue to use effective contraception for the duration of study participation and for 6 months after the final dose of study drug. Female patients must be nonlactating and have a negative serum pregnancy test result at screening and baseline.
• Male patients must agree to use effective contraception (must agree to use 2 forms of contraception, 1 of which must be a barrier method) for the duration of study participation and for 6 months after the final dose of study drug.
• Have a histologic or cytologic diagnosis of malignant solid tumor for which there are no standard of care treatment options known to confer a clinical benefit or for which the patient is ineligible or declines.
• A. For Phase 1 dose escalation: histologic or cytologic diagnosis of malignant solid tumor of any type. The Sponsor may remove specific tumor indications based on emerging, real-time study data.
• B. For Phase 1b dose expansion:
• i. Cohort A: Histologic or cytologic diagnosis of NSLC (adenocarcinoma and SCC).
• ii. Cohort B: Histologic or cytologic diagnosis of TNBC or HR positive, HER2 negative breast cancer.
• iii. Cohort C: Histologic or cytologic diagnosis of the following advanced metastatic solid tumors refractory to standard treatment: pancreatic adenocarcinoma, gastric adenocarcinoma, hepatocellular carcinoma, ovarian adenocarcinoma, and squamous cell carcinoma including, but not limited to, primary malignancies of the head and neck, esophagus, cervix, and skin. The Sponsor may add or remove specific tumor indications based on emerging, real-time study results.
• Availability of a tumor tissue sample (formalin-fixed paraffin embedded \[FFPE\]) must be confirmed for analysis of EphA5 expression based on IHC. Tumor biopsies are not required and should not be performed to assess eligibility.
• A. For Dose Escalation (Phase 1) and Dose Expansion (Phase 1b), tumor EphA5 expression will not be required for enrollment.
• For Dose Escalation (Phase 1), patients may have evaluable disease or measurable disease according to RECIST v1.1). For Dose Expansion (Phase 1b) and Phase 2, patients must have measurable disease according to RECIST v1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
• Life expectancy ≥ 3 months as assessed by the investigator.

You may not qualify if:

• Preexisting sensory neuropathy Grade ≥ 2.
• Preexisting motor neuropathy Grade ≥ 2.
• Uncontrolled central nervous system metastases.
• Use of any investigational drug within 14 days prior to the first dose of study drug.
• Any anticancer therapy within 14 days prior to the first dose of study drug, including: small molecules, immunotherapy, chemotherapy, monoclonal antibody therapy, radiotherapy, or any other agents to treat cancer (anti-hormonal therapy given for advanced prostate cancer or as adjuvant therapy for early stage, hormone receptor (HR) positive breast cancer is not considered cancer therapy for the purpose of this Protocol).
• Strong CYP3A or inducers within 14 days prior to the first dose of study drug.
• \. 7. Thromboembolic events and/or bleeding disorders 14 days (e.g., venous thromboembolism \[VTE\] or pulmonary embolism \[or PE\]) prior to the first dose of study drug.
• \. Documented history of a cerebral vascular event (stroke or transient ischemic attack), unstable angina, myocardial infarction, or cardiac symptoms (including congestive heart failure) consistent with New York Heart Association Class 3-4 within 6 months prior to the first dose of MBRC-101.
• \. A baseline QT (time from the beginning of the Q wave to the end of the T wave) interval as corrected by Fridericia's formula (QTcF) \> 470 msec.
• \. Human immunodeficiency virus (HIV) infection with 1 or more of the following: A. Acquired immunodeficiency syndrome (AIDs)-defining opportunistic infection within 6 months of the start of screening; B. A change in antiretroviral therapy within 3 months of the start of screening and viral load \> 500 copies/mL; C. Receiving antiretroviral therapy that may interfere with study drug; D. CD4 count \< 350 at screening. 11. Active or symptomatic viral hepatitis. Patients who have been properly treated for hepatitis C infection can be included if they do not have active hepatitis C.
• \. Known sensitivity to any of the ingredients of the investigational product MBRC-101.
• \. Major surgery within 28 days prior to first dose of study drug. 14. History of another malignancy within 3 years before the first dose of study drug, or any evidence of residual disease from a previously diagnosed malignancy. Allowed exceptions are patients with: A. Non-melanoma skin cancer considered completely cured; B. Localized prostate cancer treated with curative intent with no evidence of progression; C. Low-risk or very low-risk (per standard clinical guidelines) localized prostate cancer under active surveillance without immediate intent to treat; D. Malignancy that is otherwise considered cured with minimal risk of recurrence.
• \. Currently receiving systemic antimicrobial treatment for active infection (bacterial, viral, or fungal) at the time of first dose of MBRC-101. Routine antimicrobial prophylaxis is permitted.
• \. Condition or situation which, in the investigator's opinion, may put the patient at significant risk, may confound the study results, or may interfere significantly with patient's participation in the study.
• \. Any medical, psychiatric, addictive, or other kind of disorder which compromises the ability of the patient to give written informed consent and/or to comply with procedures.

Sponsors & Collaborators

• MBrace Therapeutics: lead

Study Sites (17)

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94158, United States

RECRUITING

University of Colorado, Anschutz Cancer Pavilion (ACP(

Aurora, Colorado, 80045, United States

RECRUITING

Winship Cancer Institute, Emory University

Atlanta, Georgia, 30322, United States

RECRUITING

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

RECRUITING

Horizon Oncology Research

Lafayette, Indiana, 47905, United States

COMPLETED

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

RECRUITING

Comprehensive Cancer Center of Nevada

Las Vegas, Nevada, 89169, United States

RECRUITING

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

RECRUITING

Columbia University Irving Medical Center

New York, New York, 10032, United States

RECRUITING

Carolina BioOncology Institute

Huntersville, North Carolina, 28078, United States

ACTIVE NOT RECRUITING

University of Pennsylvania, Abramson Cancer Center

Philadelphia, Pennsylvania, 19014, United States

RECRUITING

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

RECRUITING

Medical University of South Carolina (MUSC)

Charleston, South Carolina, 29425, United States

RECRUITING

PRISMA Health, Institute for Translational Oncology

Greenville, South Carolina, 29605, United States

RECRUITING

NEXT Oncology

Austin, Texas, 78758, United States

RECRUITING

NEXT Oncology

Irving, Texas, 75039, United States

RECRUITING

NEXT Oncology

Fairfax, Virginia, 22031, United States

RECRUITING

Related Publications (1)

• Staquicini FI, Tang FH, de Oliveira V, Kim SY, Chen ER, Markosian C, Staquicini DI, Wu Y, Parsons JK, Barnhart KF, Alley SC, Chen I, Arap W, Pasqualini R. First-generation and preclinical evaluation of an EphA5-targeted antibody-drug conjugate in solid tumors. J Clin Invest. 2025 Jul 15;135(14):e188492. doi: 10.1172/JCI188492. eCollection 2025 Jul 15.

  PMID: 40662373 DERIVED

MeSH Terms

Conditions

Neoplasms

Interventions

Immunoconjugates

Intervention Hierarchy (Ancestors)

Antibodies; Immunoglobulins; Serum Globulins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Globulins; Immunologic Factors; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses

Central Study Contacts

Kellogg Parsons, MD, M.H.S.

CONTACT

858-703-8086; clinicalsupport@mbracetrx.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 1, 2023
• First Posted: August 28, 2023
• Study Start: November 7, 2023
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): November 1, 2026
• Last Updated: March 2, 2026

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (17)