Page 28 - WNS 2024 e-Program - Resized and Binded

A Phase 2a Trial Testing QBS72S in Brain Metastases
Melanie Hayden Gephart, MD, PhD
Professor of Neurosurgery, Stanford University
Rukayat Taiwo, Paul M. Harary, Monica Granucci, Thy TH Trinh, Sophia
Chernikova, Kate Therkelsen, Mili Arora, Michelle E. Melisko, Michael Iv,
Hannes Vogel, Summer Han, Krishna Bharani, Seema Nagpal(Stanford)
Jaymes Holland; Gordon Ringold; Ron Weitzman (Quadriga)

Introduction: Breast cancer is the most common cause of cancer death
among women and the most common source of brain metastases.
Leptomeningeal disease (LMD), a distinct subtype of brain metastases with
approximately three-month survival and severe neurologic sequelae, is
increasingly common and has no durable treatment options. is a novel
molecule, which targets LAT-1, a known brain transporter that is also highly
expressed on metastatic cancer. QBS72S showed high CNS permeability and
pre-clinical efficacy in a mouse model of breast-to-brain LMD. We have
initiated a phase 2a trial of QBS72S in patients with brain metastases,
including LMD.
Methods/Results: A single-arm, Phase 2a study will assess the
preliminary efficacy and safety of the cytotoxic agent QBS72S for the
treatment of brain metastasis within three distinct patient cohorts: breast
parenchymal metastasis (Cohort 1), breast LMD (Cohort 2), and any primary
LMD (Cohort 3). QBS72S is a novel amino acid analogue conjugated with a
DNA alkylating moiety that leverages the blood-brain barrier-specific L-type
amino acid transporter 1 (LAT1) for active transport into the brain. All
participants will receive a once-monthly dose of intravenous QBS72S at 18
mg/m 2 .
Given the diagnostic and monitoring challenges of LMD, the primary
endpoint is overall response rate across evaluable participants in Cohort 1
based on modified Response Assessment Neuro-oncology Brain Metastases
(mRANO-BM) response criteria. Secondary endpoints include PFS, OS,
DOR, and treatment-related adverse effects. Exploratory endpoints include
correlation of LAT1 expression, CSF pharmacokinetics, and the development
of novel CSF biomarkers.
Conclusion: There remains a significant unmet need in the treatment of
brain metastases, particularly for LMD. QBS72S holds great promise for
treating patients with brain-trophic metastatic cancers. Our novel
exploratory endpoints strive to identify more rapid and reliable biomarkers
of treatment response and resistance, to increase throughput of LMD-
focused clinical trials.