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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

Phase
Phase 1/Phase 2
Sponsor
MBrace Therapeutics
Enrollment
130
Timeline
Nov 2023 → Nov 2026
About This Study

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.

Eligibility Criteria

Inclusion Criteria

  • 1Provide 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.
  • 218 years of age or older at the time of informed consent.
  • 3Female 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.
  • 4Male 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.
  • 5Have 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.
  • 6A. 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.
  • 7B. For Phase 1b dose expansion:
  • 8i. Cohort A: Histologic or cytologic diagnosis of NSLC (adenocarcinoma and SCC).
  • 9ii. Cohort B: Histologic or cytologic diagnosis of TNBC or HR positive, HER2 negative breast cancer.
  • 10iii. 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.
  • 11Availability 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.
  • 12A. For Dose Escalation (Phase 1) and Dose Expansion (Phase 1b), tumor EphA5 expression will not be required for enrollment.
  • 13For 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.
  • 14Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
  • 15Life expectancy ≥ 3 months as assessed by the investigator.
  • 16Hematologic function, as follows (no red blood cell \[RBC\] or platelet transfusions are allowed within 14 days of the first dose of MBRC-101):
  • 17A. Absolute neutrophil count (ANC) ≥ 1.0 × 109/L B. Platelet count ≥ 100 × 109/L C. Hemoglobin ≥ 9 g/dL
  • 18Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min by the CKD-EPI or similar equation or as measured by 24-hour urine collection.
  • 19Total bilirubin ≤ 1.5 × upper limit normal (ULN).
  • 20AST ≤ 3.0 × ULN.
  • 21ALT ≤ 3.0 × ULN.
  • 22International normalised ratio (INR) \< 1.5 (or ≤ 3.0 if on therapeutic anticoagulation).
  • 23Treatment with other agents for cancer, if received, must have been discontinued ≥ 2 weeks prior to first dose of study drug.
  • 24Prior 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

  • 1Preexisting sensory neuropathy Grade ≥ 2.
  • 2Preexisting motor neuropathy Grade ≥ 2.
  • 3Uncontrolled central nervous system metastases.
  • 4Use of any investigational drug within 14 days prior to the first dose of study drug.
  • 5Any 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).
  • 6Strong CYP3A or inducers within 14 days prior to the first dose of study drug.
  • 78\. 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.
  • 88\. 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.
  • 99\. 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.
  • 1010\. 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.
  • 1112\. Known sensitivity to any of the ingredients of the investigational product MBRC-101.
  • 1213\. 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.
  • 1315\. 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.
  • 1416\. 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.
  • 1517\. 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.
  • 1618\. 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.

Locations

17 sites participating in this study

Winship Cancer Institute, Emory University

Atlanta, Georgia 30322

Recruiting

Ticiana Leal, MD

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California 94158

Recruiting

Pam Munster, MD

University of Colorado, Anschutz Cancer Pavilion (ACP(

Aurora, Colorado 80045

Recruiting

Jennifer R Diamond, MD

Data sourced from ClinicalTrials.govView on ClinicalTrials.gov →