Ventana TROP2 (EPR20043) RxDx Device Receives FDA Breakthrough Device Designation for Dato-DXd Selection in NSCLC

FDA

The FDA has granted breakthrough device designation to the Ventana TROP2 (EPR20043) RxDx Assay—an artificial intelligence (AI)–driven computational pathology device—to aid in the identification of patients with previously treated advanced or metastatic nonsquamous non–small cell lung cancer (NSCLC) without actionable genomic alterations who may be candidates for treatment with datopotamab deruxtecan-dlnk (Datroway; Dato-DXd).1

The VENTANA TROP2 (EPR20043) RxDx Device is a diagnostic tool that integrates the VENTANA TROP2 (EPR20043) RxDx Assay, an immunohistochemistry (IHC) companion diagnostic, with an AI-driven digital pathology algorithm.

By analyzing whole slide images of TROP2-stained NSCLC tissue, the algorithm autonomously detects tumor cells and quantifies TROP2 IHC staining intensity in both the membrane and cytoplasm. It then calculates a normalized membrane ratio (NMR) score and classifies TROP2 expression as either positive or negative based on a predefined NMR cutoff. Notably, the device leverages quantitative continuous scoring, a computational pathology platform designed to enhance diagnostic precision compared with traditional manual scoring methods.

According to Roche, this regulatory decision marks the first breakthrough device designation granted to a computational pathology companion diagnostic, and the designation could potentially expedite the availability of an AI-driven TROP2 diagnostic tool to guide NSCLC treatment selection.

“This FDA breakthrough device designation is another example of our commitment to deliver innovation that enables more precise diagnosis in oncology,” Matt Sause, chief executive officer of Roche Diagnostics, stated in a news release. “This solution, which leverages our industry-leading expertise in companion diagnostics development, uses artificial intelligence for a greater depth of sample analysis, helping to deliver truly personalized treatment.”

In January 2025, the FDA accepted and granted priority review to a biologics license application (BLA) seeking the approval of Dato-DXd for the treatment of adult patients with locally advanced or metastatic EGFR-mutated NSCLC who have received prior systemic therapies, including an EGFR-directed therapy.1 The Prescription Drug User Fee Act action date for the BLA is July 12, 2025.2

The BLA is supported by data from the phase 2 TROPION-Lung05 trial (NCT04484142) and the phase 3 TROPION-Lung01 (NCT04656652) and phase 1 TROPION-PanTumor01 (NCT03401385) studies. Results from a pooled analysis of patients with previously treated advanced or metastatic EGFR-mutated NSCLC treated with Dato-DXd in TROPION-Lung01 and TROPION-Lung05 showed that the confirmed objective response rate (ORR; n = 117) was 42.7% (95% CI, 33.6%-52.2%), including a complete response (CR) rate of 4.3%.3

The median duration of response (DOR) was 7.0 months (95% CI, 4.2-9.8) and the disease control rate (DCR) was 86.3% (95% CI, 78.7%-92.0%). The median progression-free survival (PFS) and overall survival (OS) values were 5.8 months (95% CI, 5.4-8.2) and 15.6 months (95% CI, 13.1-19.0), respectively.

On January 17, 2025, the FDA approved Dato-DXd for the treatment of adult patients with unresectable or metastatic, hormone receptor–positive, HER2-negative breast cancer who had received prior endocrine therapy and at least 1 line of chemotherapy in the metastatic setting.4

Results from the phase 3 TROPION-Breast01 trial (NCT05104866) supported this regulatory decision, showing a median PFS of 6.9 months (95% CI, 5.7-7.4) vs 4.9 months (95% CI, 4.2-5.5) for patients treated with Dato-DXd (n = 365) vs those given chemotherapy (n = 367), respectively (HR, 0.63; 95% CI, 0.52-0.76; 2-sided P < .0001).4,5 The median OS with Dato-DXd was 18.6 months (95% CI, 17.3-20.1) compared with 18.3 months (95% CI, 17.3-20.5) with chemotherapy (HR, 1.01; 95% CI, 0.83-1.22). Notably, the 2-sided P value for OS was not statistically significant.4

VENTANA TROP2 (EPR20043) RxDx was designed to assist in the identification of patients with previously treated advanced or metastatic non-squamous NSCLC lacking actionable genomic alterations who may benefit from treatment with Dato-DXd.1 Although AI-based scoring enhances reproducibility and sensitivity, pathologists are still responsible for image review and validation. This includes assessing tumor detection adequacy and incorporating histological findings, clinical context, and appropriate controls to ensure accurate and clinically meaningful interpretation.

“This FDA breakthrough device designation underscores the potential of our computational pathology platform to enable more personalized treatment decisions for people with cancer,” Susan Galbraith, executive vice president of Oncology/Haematology Research & Development at AstraZeneca concluded in the news release.

References

1. Roche granted FDA breakthrough device designation for first AI-driven companion diagnostic for non-small cell lung cancer. News release. Roche. April 29, 2025. Accessed April 24, 2025. https://www.roche.com/media/releases/med-cor-2025-04-29
2. Datopotamab deruxtecan granted priority review in the U.S. for patients with previously treated advanced EGFR-mutated non–small cell lung cancer. News release. Daiichi-Sankyo. January 13, 2025. Accessed January 13, 2025. https://www.daiichisankyo.com/files/news/pressrelease/pdf/202501/20250113_E1.pdf
3. Ahn MJ, Sands J, Lisberg AE, et al. Efficacy and safety of datopotamab deruxtecan (Dato-DXd) in patients (pts) with previously-treated EGFR-mutated advanced non-small cell lung cancer (NSCLC): a pooled analysis of TROPION-Lung01 and TROPION-Lung05. Ann Oncol. 2024;35(suppl 4):S1630-S1631. doi:10.1016/j.annonc.2024.10.656
4. FDA approves datopotamab deruxtecan-dlnk for unresectable or metastatic, HR-positive, HER2-negative breast cancer. FDA. January 17, 2025. Accessed May 2, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-datopotamab-deruxtecan-dlnk-unresectable-or-metastatic-hr-positive-her2-negative-breast
5. Bardia A, Jhaveri K, Im S, et al. Datopotamab deruxtecan (Dato-DXd) vs chemotherapy in previously-treated inoperable or metastatic hormone receptor-positive, HER2-negative (HR+/HER2–) breast cancer (BC): Primary results from the randomised phase III TROPION-Breast01 trial. Ann Oncol. 2023;34(suppl 2):S1264-S1265. doi:10.1016/j.annonc.2023.10.015