# Imaging the multifaceted response to a bispecific antibody therapy

> **NIH NIH R01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2024 · $29,864

## Abstract

Project Summary
Resistance to the standard of care treatments contributes to mortality in patients with metastatic triple negative
breast cancer (TNBC) or non-small cell lung cancer (NSCLC). In metastatic TNBC, the epidermal growth factor
receptor (EGFR) and cytoplasmic mesenchymal-epithelial transition (cMET) receptor are both overexpressed
in the basal-like subtype of TNBC. Metastatic NSCLC often harbors mutations in the epidermal growth factor
receptor (EGFR), in which patients can develop resistance to EGFR tyrosine kinase inhibitors (TKI). MET gene
amplification is also a resistance mechanism for EGFR TKIs. To overcome resistance to EGFR TKI, a
bispecific antibody called JNJ-61186372 (BsAb) was developed that targets both EGFR and cMET receptors
simultaneously, inhibiting receptor-ligand activation and degrading these receptors upon internalization of the
bsAb. Currently, there are no effective methods to predict and monitor response to bsAb, making it difficult to
select patients most likely to respond to this new therapy in a clinical trial setting and save those unlikely to
respond from undue drug exposure. We aim to develop PET imaging biomarkers to look at the multifaceted
response to bsAb therapy: bsAb delivery to the tumor (Aim 1) and changes in individual receptor status in vivo
(Aim 2). Through correlative studies among PET imaging, response to bsAb therapy, and known genetic
mutation status in EGFR, we will produce the right PET imaging toolkit to understand the mechanisms of action
of bsAb in vivo. Our techniques can complement standard of care analysis of EGFR mutation status to select
patients most likely to respond to bsAb therapy and monitor response to treatment. This future goal will require
an IND, for which our studies will provide proof-of-feasibility in preclinical models. Ultimately, establishing our
imaging techniques as companion diagnostic agents could have high impact in accelerating FDA-approval of
bsAb for the treatment of patients with NSCLC or TNBC who have developed resistance to standard of care of
treatments.

## Key facts

- **NIH application ID:** 10656275
- **Project number:** 5R01CA255226-04
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Bernadette Marquez-Nostra
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $29,864
- **Award type:** 5
- **Project period:** 2021-07-15 → 2027-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10656275

## Citation

> US National Institutes of Health, RePORTER application 10656275, Imaging the multifaceted response to a bispecific antibody therapy (5R01CA255226-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10656275. Licensed CC0.

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