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

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.