Evidence map›Paper›PMID 40813655›Full record

ArticleBMC cancer2025

Adaptive cohort design and LAT1 expression scale: study protocol for a Phase 2a trial of QBS72S in breast cancer brain metastases.

Rukayat Taiwo, Paul M Harary, Thy T H Trinh, Monica Granucci, Sophie Bertrand, Brandon Carlson-Clarke, Sophia B Chernikova, Kate Therkelsen, Mili Arora, Michelle E Melisko and 9 more

2 registry-linked trialsAbstract readClinical Trial Protocol
PubMed Full text at PMC Publisher
In one paragraph

Article in BMC cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02977780 phase2recruitingnot on this map

INdividualized Screening Trial of Innovative Glioblastoma Therapy (INSIGhT)

TypeinterventionalSponsorDavid Reardon, MDRan2017 to 2028Enrolled460ConditionsGlioblastomaArmsTemozolomide, Neratinib, QBS10072S, Abemaciclib, CC-115
NCT05305365 phase2active not recruitingnot on this map

Phase IIa Study Assessing QBS72S For Treating Brain Metastases

TypeinterventionalSponsorStanford UniversityRan2022 to 2027Enrolled21ConditionsBrain Metastases, Breast Cancer, Lung Cancer, Leptomeningeal DiseaseArmsQBS72S
3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors.

Rukayat TaiwoDepartment of Neurosurgery, Stanford University School of Medicine, Stanford Cancer Center, 875 Blake Wilbur Dr. Clinic A MC 6560, Stanford, CA, 94305, USA.
Paul M HararyDepartment of Neurosurgery, Stanford University School of Medicine, Stanford Cancer Center, 875 Blake Wilbur Dr. Clinic A MC 6560, Stanford, CA, 94305, USA.
Thy T H TrinhDepartment of Neurosurgery, Stanford University School of Medicine, Stanford Cancer Center, 875 Blake Wilbur Dr. Clinic A MC 6560, Stanford, CA, 94305, USA.
Monica GranucciDepartment of Neurosurgery, Stanford University School of Medicine, Stanford Cancer Center, 875 Blake Wilbur Dr. Clinic A MC 6560, Stanford, CA, 94305, USA.
Sophie BertrandDepartment of Neurosurgery, Stanford University School of Medicine, Stanford Cancer Center, 875 Blake Wilbur Dr. Clinic A MC 6560, Stanford, CA, 94305, USA.
Brandon Carlson-ClarkeDepartment of Neurosurgery, Stanford University School of Medicine, Stanford Cancer Center, 875 Blake Wilbur Dr. Clinic A MC 6560, Stanford, CA, 94305, USA.
Sophia B ChernikovaDepartment of Neurosurgery, Stanford University School of Medicine, Stanford Cancer Center, 875 Blake Wilbur Dr. Clinic A MC 6560, Stanford, CA, 94305, USA.
Kate TherkelsenDepartment of Neurology and Neurological Sciences, Stanford Cancer Institute, Stanford, CA, USA.
Mili AroraDivision of Hematology and Oncology, University of California, Davis Comprehensive Cancer Center, University of California, Davis School of Medicine, Sacramento, CA, USA.
Michelle E MeliskoDivision of Hematology/Oncology, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Michael IvDepartment of Radiology, Stanford University School of Medicine, Stanford, CA, USA.
Hannes VogelDepartment of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
Summer HanQuantitative Sciences Unit, Stanford University School of Medicine, Stanford, CA, USA.
Christine XieDepartment of Neurosurgery, Stanford University School of Medicine, Stanford Cancer Center, 875 Blake Wilbur Dr. Clinic A MC 6560, Stanford, CA, 94305, USA.
Susie BrainPatient Advocate, Komen Advocates in Science, Stanford, USA.
Vivian LeePatient Advocate, Komen Advocates in Science, Stanford, USA.
Krishna L BharaniDepartment of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
Seema NagpalDepartment of Neurology and Neurological Sciences, Stanford Cancer Institute, Stanford, CA, USA.
Melanie Hayden GephartDepartment of Neurosurgery, Stanford University School of Medicine, Stanford Cancer Center, 875 Blake Wilbur Dr. Clinic A MC 6560, Stanford, CA, 94305, USA. mghayden@stanford.edu.

Funding

TOOLKIT CoreU54CA261717 · NCI · STANFORD UNIVERSITY · PI Melanie Hayden Gephart · 2021 to 2026
$8.9M
QBS10072S for the Treatment of Brain Metastatic Triple-Negative Breast CancerR44CA257579 · NCI · QUADRIGA BIOSCIENCES, INC. · PI RINGOLD, GORDON M · 2021 to 2024
$2.0M
California Breast Cancer Research Program B26TR1471NCI NIH HHS U54 CA261717NIH HHS R44CA257579Small Business Innovation Research 5R44CA257579-02
6 · The paper itself

Abstract

backgroundBreast cancer is the most common cause of cancer death among women and frequently metastasizes to the brain. Up to 30% of patients with breast-to-brain metastases will develop leptomeningeal disease (LMD), with poor survival, rapid neurologic decline, and no durable treatment options. The novel agent QBS72S, also known as QBS10072S, is designed to leverage the high expression of L-type amino acid transporter 1 (LAT1) on breast cancer cells and the blood-brain barrier. By conjugating an amino acid analogue with a DNA alkylating moiety, QBS72S can exploit LAT1 for specific delivery into the brain and metastatic tumor cells.

methodsWe designed a single-arm, Phase 2a study to test the preliminary efficacy and safety of QBS72S for breast-to-brain metastasis in two distinct cohorts: intraparenchymal metastasis (Cohort 1; no LMD), and LMD (Cohort 2; with or without intraparenchymal metastasis). The primary endpoint is overall response rate across evaluable participants in Cohort 1. Secondary endpoints include progression-free survival, overall survival, duration of response, and treatment-related adverse events in Cohort 1. Exploratory endpoints include correlation of LAT1 expression in formalin-fixed paraffin-embedded samples with treatment response, CSF pharmacokinetics, perfusion MRI, and novel CSF-based biomarkers. DISCUSSION: Adaptive clinical trial design enables rapid enrollment and tailored endpoints for patient cohorts with baseline disparate outcomes. Our LAT1 staining protocol will allow ongoing trials in glioblastoma (NCT02977780) and future studies in brain metastases to correlate LAT1 expression to drug efficacy. Our exploratory endpoints may facilitate identification of more rapid and reliable biomarkers of LMD treatment response and resistance.

trial registrationClinicalTrials.gov NCT05305365.

Indexed as

Brain NeoplasmsBreast NeoplasmsLarge Neutral Amino Acid-Transporter 1AdultClinical Trials, Phase II as TopicCohort StudiesFemaleHumansMiddle AgedLarge Neutral Amino Acid-Transporter 1SLC7A5 protein, humanBreast cancerChemotherapyExpression profilingLeptomeningeal diseaseLiquid biopsy

Identifiers

PMID40813655
PMCPMC12355770

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.