LAT1-Targeted Chemo Shows Extended Survival in Leptomeningeal Disease

Leptomeningeal disease (LMD), a complication of advanced cancer lacking approved treatments and associated with an expected survival of only 2 to 4 months, saw a signal of meaningful therapeutic benefit in interim data from a phase 2a study (NCT05305365) of QBS72S (formerly QBS10072S). The novel LAT1-targeted chemotherapeutic agent demonstrated encouraging survival rates and evidence of both radiographic stability and symptomatic improvement in heavily pretreated patients with metastatic breast cancer that had progressed to LMD.¹

In the small, single-arm, open-label study conducted at the Stanford University School of Medicine, the interim data showed a 1-month survival rate of 90%, a 3-month survival rate of 60%, and a 12-month survival rate of 40% among the treated cohort. Notably, 4 of 10 patients achieved survival beyond 12 months, including 2 identified as long-term responders. These findings suggest the potential for QBS72S to alter the historically poor trajectory of this central nervous system (CNS) manifestation of metastatic breast cancer.

"The phase 2a results provide important early clinical signals that reinforce the potential of QBS72S to meaningfully impact outcomes for patients with LMD," said Gordon Ringold, PhD, CEO of Quadriga BioSciences, in a news release. "These findings underscore the promise of our therapeutic approach and strengthen our commitment to advancing QBS72S as a treatment option for patients with LMD, for which there are no approved treatment alternatives."

Trial Design and Mechanism of Action

The phase 2a trial is designed to assess the safety, tolerability, and preliminary efficacy of QBS72S in up to 35 patients with brain metastases from breast cancer. The primary objective is to determine preliminary efficacy through overall response rate, with secondary end points including progression-free survival, overall survival (OS), duration of response, and adverse events.²

The therapeutic rationale for QBS72S is based on its novel mechanism designed to overcome a major hurdle in treating CNS malignancies: the blood-brain barrier (BBB).¹ QBS72S is a first-in-class chemotherapeutic agent engineered to mimic an aromatic amino acid. This structural homology enables the drug to exploit the LAT1 transporter, a protein highly expressed on the BBB and on the cell surfaces of many aggressive cancers, including those associated with poor prognosis. By utilizing LAT1, QBS72S gains efficient cellular uptake across the BBB and directly into rapidly proliferating cancer cells. Once intracellular, the agent induces double-stranded DNA breaks, leading to cell death. The overexpression of LAT1 by aggressive tumor cells provides a key selectivity advantage for the agent.

Efficacy and Safety Data

Beyond the significant improvement in OS rates compared to the natural history of LMD, the interim analysis reported observable radiographic stability in conjunction with improvements in neurologic and physical symptoms. The ability to observe both objective and subjective benefits in this clinically challenging population reinforces the potential of the LAT1-targeting approach to achieve therapeutically relevant drug concentrations within the CNS space.

Regarding safety, QBS72S was reported to be well tolerated in the heavily pretreated patient population. This is critical given that patients with LMD often have compromised performance status due to their advanced disease and previous systemic therapies.

REFERENCES

1. Quadriga BioSciences announces encouraging interim phase II results of LAT1-targeted QBS72S in breast cancer patients with leptomeningeal disease. News release. Quadriga BioSciences. December 3, 2025. Accessed December 4, 2025. https://tinyurl.com/2zb7yma3

2. Study assessing QBS72S for treating brain metastases. ClinicalTrials.gov. Updated October 17, 2025. Accessed December 4, 2025. https://www.clinicaltrials.gov/study/NCT05305365