MBRC-101 Shows Potential Activity, Tolerability in EphA5+ Breast Cancer

Data from a poster presented at the 2023 San Antonio Breast Cancer Symposium (SABCS) highlighted robust anti-cancer activity when MBRC-101 was administered weekly to patient-derived xenograft models of TNBC, with partial responses being observed at the 2.5 mg/kg dose and complete responses occurring at the 5 mg/kg dose.

Novel antibody MBRC-101 demonstrated exclusive binding to EphA5 and showed potentially reproducible clinical activity and tolerability in triple-negative breast cancer (TNBC) models, according to a press release on preclinical findings from MBrace Therapeutics, Inc.¹

Data from a poster presented at the 2023 San Antonio Breast Cancer Symposium (SABCS) highlighted robust anti-cancer activity when MBRC-101 was administered weekly to patient-derived xenograft models of TNBC, with partial responses being observed at the 2.5 mg/kg dose and complete responses occurring at the 5 mg/kg dose.² Additionally, treatment with MBRC-101 appeared to be tolerable and elicited no weight loss at up to 20 mg/kg. Reports also indicated that toxicity was related to the agent’s MMAE payload rather than its target.

“The data presented today further characterize the safety and activity of MBRC-101 and support its potential to effectively treat various solid tumors, including difficult-to-treat breast cancers,” Isan Chen, MD, co-founder, president, and chief executive officer at MBrace, said in the press release.¹ “We are advancing our clinical evaluation of MBRC-101 in breast cancer, as well as for patients with other EphA5-expressing solid tumor cancers for whom there is a significant need for targeted treatment options.”

Based on these preclinical findings, investigators plan to evaluate the safety and preliminary clinical activity of this agent in patients with EphA5-expressing malignant solid tumors as part of the phase 1/1b MBRC-101-001 trial (NCT06014658).²

“At MBrace, as we move into this next exciting phase of clinical development, we remain dedicated to improving outcomes for patients who are living with difficult-to-treat cancers,” Wadih Arap, MD, PhD, director of the Rutgers Cancers Institute of New Jersey at University Hospital and chief of Hematology/Oncology and founder and scientific advisor at MBrace, said in a press release on the initiation of this phase 1/1b trial.³ “MBRC-101 is a proof point of our emerging pipeline and broader vision.”

The study will include a phase 1 escalation portion assessing MBRC-101 across 4 dose levels ranging from 0.5 mg/kg to 2.0 mg/kg in 30 patients. As part of a phase 1b expansion portion, the experimental agent will be administered to a planned total of 60 patients, including those with triple-negative or hormone receptor–positive/HER2-negative breast cancer (n = 20), non–small cell lung cancer (NSCLC; n = 20), and other EphA5-positive tumors based on immunohistochemistry analysis (n = 20).

The study’s primary end points include identifying the maximum tolerated dose, dose-limiting toxicities, adverse effects (AEs), serious AEs, and clinical laboratory tests in phase 1; AEs, SAEs, clinical laboratory tests, and investigator-assessed objective response rate (ORR) based on RECIST v1.1 criteria will be the primary end points of the phase 1b portion of the study. Secondary primary end points will include unconjugated MMAE blood concentrations and EphA5 expression.

Patients 18 years and older with a histologically or cytologically confirmed malignant solid tumor for which there are no standard treatment options are eligible to enroll on the study. Other eligibility criteria include having available tumor tissue samples, an ECOG performance status of 0 to 2, a life expectancy of at least 3 months, and adequate hematologic function.

References

1. MBrace Therapeutics presents preclinical data demonstrating potential of novel antibody drug conjugate at 2023 San Antonio Breast Cancer Symposium. News release. MBrace Therapeutics, Inc. December 7, 2023. Accessed December 19, 2023. https://bit.ly/41wcHHp
2. Staquicini FI, Tang HF, de Oliveira V, et al. MBRC-101: a novel antibody-drug conjugate (ADC) targeting the membrane-associated tyrosine kinase receptor EphA5 in breast cancer. Presented at the 2023 San Antonio Breast Cancer Symposium; December 5-9, 2023; San Antonio, TX; abstract PO3-18-04.
3. MBrace Therapeutics announces initiation of patient dosing in phase 1 clinical trial evaluating investigational antibody-drug conjugate MBRC-101. News release. MBrace Therapeutics, Inc. December 19, 2023. Accessed December 19, 2023. https://bit.ly/4aoGJRb