TROPION-Lung01 Trial Shows AstraZeneca's QCS Platform Boosts NSCLC Patient Outcomes with Datopotamab Deruxtecan

Image Credit: Adobe Stock Images/Ziyan

Results from an exploratory analysis of the TROPION-Lung01 Phase III clinical trial found that AstraZeneca’s quantitative continuous scoring (QCS) platform helped to significantly improve responses to datopotamab deruxtecan (Dato-DXd) compared to docetaxel in non-small cell lung cancer (NSCLC) tumors. According to the company, the results were particularly noticeable in patients with nonsquamous NSCLC, in whom Dato-DXd reduced disease progression or death by 43%.¹

“TROP2 is broadly expressed on solid tumor cells, including non-small cell lung cancer, but it has yet to be established as a predictive biomarker for any TROP2-directed antibody drug conjugate. We have shown with this analysis that the more precise quantitative measurement of TROP2 on and inside tumour cells, enabled by AstraZeneca’s computational pathology platform, can identify which patients with non-small cell lung cancer are most likely to benefit from treatment with datopotamab deruxtecan,” said trial investigator Marina Garassino, MD, The University of Chicago, professor of Medicine, in a press release.

The global, randomized, multicenter, open-label TROPION-Lung01 trial evaluated the efficacy and safety of Dato-DXd (6.0 mg/kg) versus docetaxel (75 mg/m2) in adult patients with locally advanced or metastatic NSCLC, with and without actionable genomic alterations, who require systemic therapy following prior treatment. The trial included an estimated 600 patients across Asia, Europe, North America, Oceania, and South America. The primary endpoints were progression-free survival (PFS) as assessed by blinded independent central review (BICR) and overall survival (OS). Notable secondary endpoints included investigator-assessed PFS, objective response rate, duration of response, time to response, disease control rate as assessed by both BICR and investigator, and safety.

Results demonstrated that QCS provided more accurate predictive insights than conventional immunohistochemistry-based methods. Additionally, 66% of nonsquamous NSCLC patients were considered to be TROP2-QCS biomarker-positive, compared to 44% for squamous NSCLS patients. The median PFS for Dato-DXd was 6.9 months compared to docetaxel in TROP2-QCS biomarker-positive patients. In TROP2-QCS biomarker-negative patients, median PFS for Dato-DXd was 2.9 months compared to 4 months for docetaxel.

No new safety signals were identified in the biomarker evaluable population. Rates of grade 3 or higher treatment-related adverse events (TRAEs) were similar regardless of TROP2 status. Thirty-percent of participants with TROP2-QCS biomarker positive tumors experienced grade 3 or higher TRAEs in the Dato-DXd arm, while 46% of patients in the docetaxel arm experienced the same.¹

“This analysis demonstrates the power of our computational pathology platform to discover new predictive biomarkers and substantially improve patient selection for datopotamab deruxtecan. It also has great potential to help more precisely select patients across our broader antibody drug conjugate portfolio. ​We are excited to extend our collaboration with Roche Tissue Diagnostics with the aim of validating this exploratory approach for TROP2, developing the companion diagnostic and bringing it to the clinic as quickly as possible,” said Susan Galbraith, EVP, Oncology R&D, AstraZeneca, in the press release.

Dato-DXd was discovered by Daiichi Sankyo and is being co-developed by AstraZeneca and Daiichi Sankyo. Aiming to further develop and commercialize the TROP2-QCS biomarker for broader clinical use, AstraZeneca is also partnering with Roche Tissue Diagnostics to co-develop a companion diagnostic through the use of the QCS platform, which will be deployed within Roche's navify Digital Pathology image management system.¹

“Our collaboration with AstraZeneca continues to push the boundaries of traditional cancer diagnostics. By developing an innovative Al tool that goes beyond human capabilities, the solution will be able to help determine which cancer patients are most likely to benefit from targeted therapies, potentially improving patient care,” said Jill German, head, Roche Tissue Diagnostics, in the press release.

Reference

1. Novel computational pathology-based TROP2 biomarker for datopotamab deruxtecan was predictive of clinical outcomes in patients with non-small cell lung cancer in TROPION-Lung01 Phase III trial. AstraZeneca. September 8, 2024. Accessed September 9, 2024. https://www.astrazeneca.com/media-centre/press-releases/2024/novel-computational-pathology-based-trop2-biomarker-for-dato-dxd-was-predictive-of-clinical-outcomes-in-patients-with-nsclc-in-tropion-lung01-phase-iii-trial.html