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Evaluating MBRC-101 for advanced solid tumors that don't respond to standard treatments

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

PHASE1; PHASE2 · MBrace Therapeutics · NCT06014658

This study is testing a new treatment called MBRC-101 to see if it can help people with advanced solid tumors that haven't responded to other therapies.

Quick facts

PhasePHASE1; PHASE2
Study typeInterventional
Enrollment130 (estimated)
Ages18 Years and up
SexAll
SponsorMBrace Therapeutics (industry)
Drugs / interventionsbrentuximab, polatuzumab, enfortumab, disitamab, tisotumab, chemotherapy, immunotherapy
Locations17 sites (San Francisco, California and 16 other locations)
Trial IDNCT06014658 on ClinicalTrials.gov

What this trial studies

This clinical trial is a first-in-human, open-label study assessing the safety, pharmacokinetics, and preliminary efficacy of MBRC-101 in patients with advanced metastatic solid tumors that are refractory to standard therapies. The trial consists of three phases: Phase 1 focuses on determining the maximum tolerated dose and optimal biologically relevant doses, while Phase 1b evaluates safety and preliminary clinical activity in expanded cohorts. Phase 2 will assess the efficacy of MBRC-101 at the recommended dose based on findings from earlier phases. Safety monitoring will be conducted throughout the trial by a dedicated committee.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with advanced or metastatic solid tumors that have not responded to standard therapies.

Not a fit: Patients with tumors that express EphA5 may not benefit from this study, as their expression will be assessed retrospectively.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced solid tumors that have not responded to existing treatments.

How similar studies have performed: Other studies have shown promise with similar antibody-drug conjugate approaches, indicating potential for success in this novel treatment.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion 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.

   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.
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.

   A. For Dose Escalation (Phase 1) and Dose Expansion (Phase 1b), tumor EphA5 expression will not be required for enrollment.
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):

    A. Absolute neutrophil count (ANC) ≥ 1.0 × 109/L B. Platelet count ≥ 100 × 109/L C. Hemoglobin ≥ 9 g/dL
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.

Prior ADC therapy is allowed. Prior agents conjugated to MMAE are allowed for Phase 1 but not for Phase 1b or Phase 2. These exclusionary agents include brentuximab vedotin, polatuzumab vedotin, enfortumab vedotin, disitamab vedotin, tisotumab vedotin, and any MMAE-conjugated agents approved subsequent to the publication of this Protocol.

Exclusion Criteria:

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.

Where this trial is running

San Francisco, California and 16 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.

View on ClinicalTrials.gov →

Conditions: Cancer

Last reviewed 2026-05-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.