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

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.

Phase 1, dose escalation, will enroll approximately 30 patients with advanced or metastatic solid tumors refractory to standard therapy. EphA5 expression will not be required for enrollment into Phase 1 but will be assessed retrospectively. Phase1b, the dose expansion phase will evaluate the safety and preliminary clinical activity of MBRC-101 at potential OBRDs and dosing regimens in patients with advanced or metastatic solid tumors refractory to standard therapy. Phase 1b will enroll 3 expansion cohorts of ≈ 20 patients per cohort (n ≈ 60 total). The Phase 2 portion will begin when the RP2D has been determined from Phase 1b and all Phase 1b patients have completed at least two cycles of treatment or have discontinued from the study prior to completing two cycles of treatment. Phase 2 will evaluate anti-tumor activity and safety of the RP2D determined during Phase 1b. Phase 2 will focus on a specific tumor type identified during Phase 1/1b and will enroll approximately 30 patients. Safety will be monitored by the Safety Review Committee (SRC) at each dose escalation in Phase 1 and at regular intervals throughout Phase 1b and Phase 2. Overall Response Rate (ORR), Progression Free Survival (PFS), Response Rate (RR), Overall Survival (OS), Disease Control Rate (DCR), and Complete and Partial response (CR and PR) will be used to evaluate efficacy per RECIST v1.1 criteria based on the results of positron emission tomography and computed tomography (PET-CT), computerized tomography (CT), and magnetic resonance imaging (MRI) scans.