Phase 1/2 Dose Finding, Safety and PK Study in Advanced Refractory Solid Tumors

Description

This is a multicenter, open-label FIH, Phase 1a (dose escalation), Phase 1b (dose expansion) and Phase 2 study in patients with advanced metastatic solid tumors refractory to standard treatment.

Phase 1a will characterize safety and identify potential optimal biologically relevant doses (OBRDs), Recommended Phase 2 Doses (RP2Ds), and the maximum tolerated dose (MTD) of MBRC-201 at one or more dosing regimens.

Phase 1b will evaluate the safety and preliminary clinical activity of MBRC-201 at the potential OBRDs, RP2Ds, and dosing regimens identified in Phase 1a. The initial Phase 2 portion will begin when the RP2D has been determined from Phase 1a and Phase1b data. Phase 1b will enroll at least 4 expansion cohorts of approximately 20 patients per cohort (n ≈ 80 total) with the following tumor types: patients with mCRPC with confirmed adenocarcinoma histology, patients with advanced metastatic NSCLC refractory to standard treatment, patients with advanced metastatic breast cancer (TNBC, HR+/HER2-low or -negative, or HR-/HER2-low) refractory to standard treatment, and patients with advanced metastatic CRC or PDAC refractory to standard treatment.

The initial Phase 2 will enroll approximately 30 patients to further evaluate antitumor activity and safety of MBRC-201 at the RP2D determined during Phase 1b. Phase 2 will enroll patients in tumor-specific cohorts from the indications evaluated in Phase 1a/1b.

Phase 1a, Phase 1b and Phase 2 will characterize single and multiple-dose PK profiles and evaluate incidence and persistence of anti-MBRC-201 antibody (Ab) [ADA] formation. Safety will be assessed at each dose escalation in Phase 1a and ad hoc throughout Phase 1b and Phase 2.

A Safety Review Committee (SRC), consisting of the site investigators and representatives from the Sponsor will monitor patient safety and make dosing recommendations throughout the study.

The duration of the study (e.g., from the first patient enrolled through completion of LTFU data collection) is estimated to be approximately 48 months. There will also be long-term follow-up (LTFU) for safety, disease status, and survival assessments, which will continue until death or lost to follow-up, withdrawal of consent for further follow-up, or study termination whichever occurs first