RECRUITING

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

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

A Multicenter, Open-label, Phase 1/1b / Phase 2 Dose Finding, Safety, and Pharmacokinetic Study of MBRC-101, an Anti-EphA5 Monomethyl Auristatin E (MMAE) Antibody Drug Conjugate, in Advanced Refractory Solid Tumors

Quick Facts

Study Start:2023-11-07

Study Completion:2026-11

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06014658

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. 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. 2. 18 years of age or older at the time of informed consent. 3. 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. 4. 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. 5. 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. 6. 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. 7. 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. 8. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2. 9. Life expectancy ≥ 3 months as assessed by the investigator. 10. Hematologic function, as follows (no red blood cell \[RBC\] or platelet transfusions are allowed within 14 days of the first dose of MBRC-101): 11. Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min by the CKD-EPI or similar equation or as measured by 24-hour urine collection. 12. Total bilirubin ≤ 1.5 × upper limit normal (ULN). 13. AST ≤ 3.0 × ULN. 14. ALT ≤ 3.0 × ULN. 15. International normalised ratio (INR) \< 1.5 (or ≤ 3.0 if on therapeutic anticoagulation). 16. Treatment with other agents for cancer, if received, must have been discontinued ≥ 2 weeks prior to first dose of study drug.	1. Preexisting sensory neuropathy Grade ≥ 2. 2. Preexisting motor neuropathy Grade ≥ 2. 3. Uncontrolled central nervous system metastases. 4. Use of any investigational drug within 14 days prior to the first dose of study drug. 5. 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). 6. Strong CYP3A or inducers within 14 days prior to the first dose of study drug. 8. 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. 8. 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. 9. 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. 10. 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. 12. Known sensitivity to any of the ingredients of the investigational product MBRC-101. 13. 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. 15. 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. 16. 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. 17. 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. 18. Active ocular surface disease at baseline or any components of the ophthalmologic history which, in the investigator's opinion, may place the patient at significant risk.

Inclusion Criteria

Exclusion Criteria

1. 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.
2. 18 years of age or older at the time of informed consent.
3. 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.
4. 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.
5. 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.
6. 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.
7. 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.
8. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
9. Life expectancy ≥ 3 months as assessed by the investigator.
10. Hematologic function, as follows (no red blood cell \[RBC\] or platelet transfusions are allowed within 14 days of the first dose of MBRC-101):
11. Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min by the CKD-EPI or similar equation or as measured by 24-hour urine collection.
12. Total bilirubin ≤ 1.5 × upper limit normal (ULN).
13. AST ≤ 3.0 × ULN.
14. ALT ≤ 3.0 × ULN.
15. International normalised ratio (INR) \< 1.5 (or ≤ 3.0 if on therapeutic anticoagulation).
16. Treatment with other agents for cancer, if received, must have been discontinued ≥ 2 weeks prior to first dose of study drug.

1. Preexisting sensory neuropathy Grade ≥ 2.
2. Preexisting motor neuropathy Grade ≥ 2.
3. Uncontrolled central nervous system metastases.
4. Use of any investigational drug within 14 days prior to the first dose of study drug.
5. 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).
6. Strong CYP3A or inducers within 14 days prior to the first dose of study drug.
8. 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.
8. 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.
9. 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.
10. 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.
12. Known sensitivity to any of the ingredients of the investigational product MBRC-101.
13. 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.
15. 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.
16. 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.
17. 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.
18. Active ocular surface disease at baseline or any components of the ophthalmologic history which, in the investigator's opinion, may place the patient at significant risk.

Contacts and Locations

Study Contact

Kellogg Parsons, MD, M.H.S.

CONTACT

858-703-8086

clinicalsupport@mbracetrx.com

Study Locations (Sites)

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94158

United States

Horizon Oncology Research

Lafayette, Indiana, 47905

United States

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903

United States

Carolina BioOncology Institute

Huntersville, North Carolina, 28078

United States

PRISMA Health, Institute for Translational Oncology

Greenville, South Carolina, 29605

United States

NEXT Oncology

Austin, Texas, 78758

United States

NEXT Oncology

Irving, Texas, 75039

United States

NEXT Oncology

Fairfax, Virginia, 22031

United States

Collaborators and Investigators

Sponsor: MBrace Therapeutics

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-11-07

Study Completion Date2026-11

Study Record Updates

Study Start Date2023-11-07

Study Completion Date2026-11

Terms related to this study

Additional Relevant MeSH Terms

Cancer