A collaboration spearheaded by Danaher is focusing on refining HER2 testing methodologies to better identify breast cancer patients who are likely to respond to antibody-drug conjugates (ADCs). The initiative centers around a novel, high-sensitivity HER2 assay developed in Dr. David Rimm's lab at Yale, with the goal of improving the precision and reliability of HER2 assessment in clinical settings. This effort addresses a critical need for more accurate diagnostic tools in the era of targeted cancer therapies.
Improving HER2 Detection
Traditional HER2 testing methods often rely on subjective assessment by pathologists, which can lead to variability and reduced sensitivity. Dr. Rimm's assay introduces a quantitative approach by using immunofluorescence to measure HER2 antibody binding, comparing it against a standard curve. "Our solution doesn’t force the pathologist to judge the level, but instead utilizes their ability to differentiate what's cancer and what's not," Dr. Rimm explained. This method reportedly increases sensitivity by approximately tenfold compared to average HER2 tests.
Overcoming Bottlenecks in Assay Availability
Despite its enhanced sensitivity, the Rimm lab faced challenges in making the assay widely accessible. Certification for clinical use took nearly two years, and current capacity is limited to about 50 tests per month, a small fraction of the demand for the approximately 240,000 breast cancer patients in the US annually. The Danaher Beacons program aims to address this bottleneck by funding the development of a standardized, commercially available product.
Danaher's Role and Clinical Trial
Rob Monroe, Chief Scientific Officer, Oncology for Danaher Diagnostics, emphasized the potential of the assay in the context of ADCs: "With the rise of ADCs, we need assays that are quantitative and more sensitive to identifying the patients most likely to benefit from these therapies." Danaher's involvement includes collaboration between Leica Biosystems to standardize the assay for global distribution and Cepheid to support a clinical trial. The clinical trial, in collaboration with Angela DeMichele, MD, of the Perelman School of Medicine, Eleanor Taranto, MD at the University of Pennsylvania, and the Translational Breast Cancer Research Consortium (TBCRC), will evaluate the assay's efficacy in predicting response to HER2-targeted ADCs.
Comparative Analysis of HER2 Measurement Technologies
An innovative aspect of the clinical trial is the comparison of two complementary technologies: Dr. Rimm's protein-based assay and Cepheid's STRAT4 assay, which measures HER2 RNA levels. This head-to-head comparison aims to determine the optimal method for identifying patients most likely to respond to HER2-targeted ADCs. "This could never be done with two independent companies and really highlights the value of Danaher," Dr. Rimm noted.
The development of companion diagnostics like this HER2 assay is crucial for realizing the promise of precision medicine, ensuring that patients receive the right treatment at the right time.
