Advancing Biomarker-Driven Strategies in NSCLC: Exploring the Emerging Role of QCS and TROP2 NMR - Episode 7
Prospective Evaluation of TROP2 NMR in Ongoing Trials: Key Data on the Horizon and Remaining Questions
Panelists discuss several ongoing clinical trials, including AVANZAR and TROPION-Lung10, that are investigating the predictive utility of TROP2 normalized membrane ratio (NMR) in guiding treatment with datopotamab deruxtecan combinations in lung cancer while highlighting advances in artificial intelligence (AI)-driven pathology to refine biomarker assessments and emphasizing the need for prospective validation to establish NMR’s role in clinical practice.
Several ongoing clinical trials are poised to shed light on the use of TROP2 NMR as a predictive biomarker in lung cancer treatment. One notable study is AVANZAR, a first-line trial comparing the combination of datopotamab deruxtecan, durvalumab, and platinum-based chemotherapy against pembrolizumab with platinum-based chemotherapy in patients with non–small cell lung cancer without actionable genomic alterations. This trial, designed before some key prior data emerged, includes a squamous population whose enrollment has since been halted. Importantly, the primary end points focus on progression-free and overall survival in the NMR-positive subgroup, emphasizing the potential of this AI-driven biomarker in guiding frontline treatment decisions.
Another trial, TROPION-Lung10, investigates the combination of datopotamab deruxtecan with a PD-1/TIGIT bispecific antibody vs pembrolizumab alone in patients with high PD-L1 expression and no actionable mutations. This study highlights a growing interest in combining novel antibody-drug conjugates with immune checkpoint inhibitors to improve outcomes. From a pathology perspective, ongoing advances in AI and computational pathology promise to refine biomarker assays further by accounting for histological subtypes and cellular heterogeneity, which may help predict responses more precisely across different cancer subtypes.
Despite recent FDA approval of datopotamab deruxtecan for EGFR-mutant non–small cell lung cancer (an indication currently not linked to NMR scoring), key questions remain about the biomarker’s broader clinical use. Early data suggest that EGFR-positive tumors may have higher NMR scores and potentially greater benefit from the drug, but this is still speculative and requires validation in larger, prospective trials. The oncology community is eagerly awaiting results from studies like AVANZAR, which incorporate predefined NMR testing hypotheses. These outcomes will be critical in determining whether TROP2 NMR can become a reliable tool in routine clinical practice, guiding personalized treatment strategies and improving patient outcomes.
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