Abstract 2038: Antibody Drug Conjugates Treatment Response Score (ADC TRS) for predicting ADC treatment response

Abstract Background: Predictive biomarkers for multiple ADCs/tumor types (beyond 3+ HER2 IHC) are lacking. We previously reported the discovery of ADC TRS—an algorithm combining individual ADC target expression, proliferation, and adhesion by RNAseq to predict ADC clinical benefit across tumor types/targets—and association with OS after ADC treatment (Abstract 3140, ASCO 2024). Here we evaluated the final ADC TRS biomarker (ADC-specific; tuned on >100 tumor type/ADC RRs) by a qRT-PCR based clinical trial assay (CTA) for predicting ADC clinical benefit. Methods: Adults in the Kaiser Permanente Northern California (KPNC) system with advanced bladder or breast cancer in an observational trial (NCT03061305) who were treated with an approved ADC (enfortumab vedotin [EV], sacituzumab govitecan [SG] or trastuzumab deruxtecan [T-DXd]; first dose by Apr. 21, 2023) with valid CTA TRS results from FFPE tissue (collected prior to 1st ADC treatment) were eligible; patients with prior trastuzumab or hormonal (between tissue collection/ ADC start) treatment were excluded. KPNC oncologists (blinded to ADC TRS status) determined best response to therapy from chart review. ADC TRS status (+ vs. -) / response data were merged by the KPNC statistician and analyzed per a prespecified plan. Results: A total of 117 KPNC patients with advanced bladder (n=58 [50%]) or breast (n=59 [50%]) cancer treated with an approved ADC (n= 56 [48%], 47 [40%], and 14 [12%] EV, SG, and T-DXd, respectively) were evaluable for TRS and RR. As shown in the Table, TRS+ status was associated with significantly higher RR and longer PFS and OS for approved ADC treatment; results were generally similar across ADCs and tumor type. Conclusions: By a qRT-PCR based CTA, TRS+ status was associated with improved RR, PFS and OS for approved ADCs in an observational cohort of patients with advanced bladder or breast cancer. Prospective validation for approved and/or investigational ADCs is warranted. Citation Format: Sachdev P. Thomas, Laurel A. Habel, Jennifer M. Suga, Ninah Achacoso, Joshua R. Nugent, Chen Jiang, Elaine Chung, Stephanie Bush, Michael D. Nitchie, Katarina M. Robinson, Jasie Inman, Ryan White, Komal Plouffe, Daniel R. Rhodes, Scott A. Tomlins, Bryan Johnson. Antibody Drug Conjugates Treatment Response Score (ADC TRS) for predicting ADC treatment response [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2038.