Abstract 2911: Prevalence of potential antibody drug conjugate targets and co-expression with PD-L1 in breast cancer and lung cancer patients with clinical response information
Authors: Cumberbatch Marie , Kim Woo Ho , Bhagat Milan , Cogswell John 
Published: March 2024

Breast and non-small cell lung cancer (NSCLC) are two of the most important diseases for antibody drug conjugate (ADC) development. ADCs targeting HER2 and TROP2 are currently approved in select breast and lung subgroups with ADC’s to many other tumor targets currently in clinical development. Based on TCGA mRNA expression data, ADC tumor targets currently under investigation for treatment of solid tumors have variable overlap in breast and lung cancers, however little is known about the overlap of ADC targets with PD-L1 which is a predictive biomarker in TNBC and for pembrolizumab monotherapy. In the current study, the prevalence and co-expression of ADC targets (HER2, TROP2, Nectin-4, B7-H3, B7-H4, HER3, FOLR1) were investigated in the context of PD-L1 status and clinical response data for standard-of-care (SOC) and immunotherapy, in breast and NSCLC cancer subtypes. Tissue microarrays (TMAs) comprising treatment naïve tumor samples (1mm cores) and including TNBC (26 patients), ER+ BC (90 patients), and NSCLC (adeno & squamous subtypes; 146 patients), all with full clinical follow-up information, were examined by immunohistochemistry (IHC) in serial sections for each ADC target and PD-L1, applying widely used and well optimized IHC assays on the Ventana and Dako Link 48 platforms. Established scoring methods were employed for analysis of PD-L1 and HER2, except for the addition of an exploratory ultra-low score for HER2. All other ADC targets were scored by digital image analysis to deliver percentage positive tumor expression at high (3+), moderate (2+), weak (1+) and negative (0) intensities. Taken together, this analysis revealed variable prevalence for each target in breast and lung cancer histologies by subtype, including differing overlap between ADC targets within tumor indications. In addition, prevalence of each ADC target in breast cancer characterized by HR status and HER2 subgroups (HER2-positive, low, ultra-low, negative) indicated potential opportunities for ADC clinical development in these subgroups. Co-prevalence of the selected ADC targets with PD-L1 CPS&gt;10 (predictive for Pembrolizumab response in TNBC) and PD-L1 CPS categories of interest for NSCLC revealed patterns of expression in support of combination therapies. Furthermore, expression and co-prevalence data for each ADC target +/- PD-L1 was characterized in association with response to immunotherapy or other SOC. In summary, these data provide better understanding of which breast and lung cancer subtypes express the selected ADC targets uniquely and competitively which may be key to future clinical and diagnostic development.

Citation Format: Marie Cumberbatch, Woo Ho Kim, Milan Bhagat, John Cogswell. Prevalence of potential antibody drug conjugate targets and co-expression with PD-L1 in breast cancer and lung cancer patients with clinical response information [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2911.