Safety & PK of MBRC-101 in Advanced Refractory Solid Tumors
- Conditions
- Cancer
- Registration Number
- NCT06014658
- Lead Sponsor
- MBrace Therapeutics
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- Not specified
Inclusion Criteria:<br><br> 1. Provide written consent on an Informed Consent Form (ICF), approved by an<br> Institutional Review Board (IRB)/Independent Ethics Committee (IEC), prior to any<br> study-specific evaluation. Patients should have the ability to read and understand<br> the ICF, ask for any clarifications from the study staff, and be able to comply with<br> all planned study procedures.<br><br> 2. 18 years of age or older at the time of informed consent.<br><br> 3. Female patients must be at least 2 years postmenopausal (defined as 2 years without<br> menses), surgically sterile (at least 6 months prior to dosing; must be documented)<br> or practicing effective contraception (must agree to use 2 forms of contraception, 1<br> of which must be a barrier method) and willing to continue to use effective<br> contraception for the duration of study participation and for 6 months after the<br> final dose of study drug. Female patients must be nonlactating and have a negative<br> serum pregnancy test result at screening and baseline.<br><br> 4. Male patients must agree to use effective contraception (must agree to use 2 forms<br> of contraception, 1 of which must be a barrier method) for the duration of study<br> participation and for 6 months after the final dose of study drug.<br><br> 5. Have a histologic or cytologic diagnosis of malignant solid tumor for which there<br> are no standard of care treatment options known to confer a clinical benefit or for<br> which the patient is ineligible or declines.<br><br> A. For Phase 1 dose escalation: histologic or cytologic diagnosis of malignant solid<br> tumor of any type. The Sponsor may remove specific tumor indications based on<br> emerging, real-time study data.<br><br> B. For Phase 1b dose expansion:<br><br> i. Cohort A: Histologic or cytologic diagnosis of NSLC (adenocarcinoma and SCC).<br><br> ii. Cohort B: Histologic or cytologic diagnosis of TNBC or HR positive, HER2<br> negative breast cancer.<br><br> iii. Cohort C: Histologic or cytologic diagnosis of the following advanced<br> metastatic solid tumors refractory to standard treatment: pancreatic adenocarcinoma,<br> gastric adenocarcinoma, hepatocellular carcinoma, ovarian adenocarcinoma, and<br> squamous cell carcinoma including, but not limited to, primary malignancies of the<br> head and neck, esophagus, cervix, and skin. The Sponsor may add or remove specific<br> tumor indications based on emerging, real-time study results.<br><br> 6. For Phase 1 and Phase 1b, availability of a tumor tissue sample (formalin-fixed<br> paraffin embedded [FFPE]) must be confirmed for analysis of EphA5 expression based<br> on IHC. Tumor biopsies are not required and should not be performed to assess<br> eligibility.<br><br> A. For Dose Escalation (Phase 1) and Dose Expansion (Phase 1b), tumor EphA5<br> expression will not be required for enrollment.<br><br> 7. For Dose Escalation (Phase 1), patients may have evaluable disease or measurable<br> disease according to RECIST v1.1). For Dose Expansion (Phase 1b), patients must have<br> measurable disease according to RECIST v1.1.<br><br> 8. Eastern Cooperative Oncology Group (ECOG) performance status = 2.<br><br> 9. Life expectancy = 3 months as assessed by the investigator.<br><br> 10. Hematologic function, as follows (no red blood cell [RBC] or platelet transfusions<br> are allowed within 14 days of the first dose of MBRC-101):<br><br> A. Absolute neutrophil count (ANC) = 1.0 × 109/L B. Platelet count = 100 × 109/L C.<br> Hemoglobin = 9 g/dL<br><br> 11. eGFR = 30 mL/min by the CKD-EPI or similar equation or as measured by 24 hour urine<br> collection.<br><br> 12. Total bilirubin = 1.5 × upper limit normal (ULN).<br><br> 13. AST = 3.0 × ULN.<br><br> 14. ALT = 3.0 × ULN.<br><br> 15. International normalised ratio (INR) < 1.5 (or = 3.0 if on therapeutic<br> anticoagulation).<br><br> 16. Treatment with other agents for cancer, if received, must have been discontinued = 2<br> weeks prior to first dose of study drug.<br><br>Prior ADC therapy is allowed. Prior agents conjugated to MMAE are allowed for Phase 1 but<br>not Phase 1b.<br><br>Exclusion Criteria:<br><br> 1. Preexisting sensory neuropathy Grade = 2.<br><br> 2. Preexisting motor neuropathy Grade = 2.<br><br> 3. Uncontrolled central nervous system metastases<br><br> 4. Use of any investigational drug within 14 days prior to the first dose of study<br> drug.<br><br> 5. Any anticancer therapy within 14 days prior to the first dose of study drug,<br> including: small molecules, immunotherapy, chemotherapy, monoclonal antibody<br> therapy, radiotherapy, or any other agents to treat cancer (anti-hormonal therapy<br> given for advanced prostate cancer or as adjuvant therapy for early stage, hormone<br> receptor (HR) positive breast cancer is not considered cancer therapy for the<br> purpose of this protocol).<br><br> 6. Patients with immunotherapy related AEs requiring high doses of steroids (= 40<br> mg/day of prednisone) are not eligible.<br><br> 7. Strong CYP3A or inducers within 14 days prior to the first dose of study drug.<br><br> 8. Thromboembolic events and/or bleeding disorders = 14 days (e.g., venous<br> thromboembolism [VTE] or pulmonary embolism [or PE]) prior to the first dose of<br> study drug.<br><br> 9. Documented history of a cerebral vascular event (stroke or transient ischemic<br> attack), unstable angina, myocardial infarction, or cardiac symptoms (including<br> congestive heart failure) consistent with New York Heart Association Class 3-4<br> within 6 months prior to the first dose of MBRC-101.<br><br> 10. A baseline QT (time from the beginning of the Q wave to the end of the T wave)<br> interval as corrected by Fridericia's formula (QTcF) > 470 msec.<br><br> 11. Human immunodeficiency virus (HIV) infection with 1 or more of the following:<br><br> A. Acquired immunodeficiency syndrome (AIDs)-defining opportunistic infection within<br> 6 months of the start of screening; B. A change in antiretroviral therapy within 3<br> months of the start of screening and viral load > 500 copies/mL; C. Receiving<br> antiretroviral therapy that may interfere with study drug; D. CD4 count < 350 at<br> screening.<br><br> 12. Active or symptomatic viral hepatitis. Patients who have been properly treated for<br> hepatitis C infection can be included if they do not have active hepatitis C.<br><br> 13. Known sensitivity to any of the ingredients of the investigational product MBRC-101.<br><br> 14. Major surgery within 28 days prior to first dose of study drug.<br><br> 15. History of another malignancy within 3 years before the first dose of study drug, or<br> any evidence of residual disease from a previously diagnosed malignancy. Allowed<br> exceptions are patients with:<br><br> A. Non-melanoma skin cancer considered completely cured; B. Localized prostate<br> cancer treated with curative intent with no evidence of progression; C. Low-risk or<br> very low-risk (per standard clinical guidelines) localized prostate cancer under<br> active surveillance without immediate intent to treat; D. Malignancy that is<br> otherwise considered cured with minimal risk of recurrence.<br><br> 16. Currently receiving systemic antimicrobial treatment for active infection<br> (bacterial, viral, or fungal) at the time of first dose of MBRC-101. Routine<br> antimicrobial prophylaxis is permitted.<br><br> 17. For Phase 1b dose expansion, prior ADC therapy is not allowed if the agent is<br> conjugated to MMAE. Prior agents conjugated to MMAE are allowed fo
Not provided
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Occurrence of treatment-emergent adverse events (TEAEs);Occurrence of dose limiting toxicities (DLTs) during the DLT evaluation period
- Secondary Outcome Measures
Name Time Method Objective Response Rate (ORR);Duration of Response (DOR);Progression-Free Survival (PFS);Disease Control Rate (DCR)