TROPION-Lung01 – A race still not yet won
Partners AstraZeneca and Daiichi Sankyo have announced high-level results for the ongoing Phase 3 TROPION-Lung01 clinical trial of TROP2-targeting ADC datopotamab deruxtecan (Dato-DXd). The trial has been one of this year’s most eagerly anticipated readouts and seeks to establish monotherapy Dato-DXd vs the current standard of care chemotherapy, docetaxel, in patients with locally advanced or metastatic NSCLC who have been treated with at least one prior therapy.
Despite the highly anticipated nature of this readout, these interim results have fallen short of providing a clear win for the regimen; While the trial met its PFS dual primary endpoint, with a trend toward significance for the as-yet still immature OS data, lack of numerical evidence or strong commentary within the official release makes it uncertain as to what degree of clinical benefit the regimen will provide vs docetaxel. Additionally, though the official release states that the safety profile was largely consistent with previous trials including with regard to interstitial lung disease, Grade 5 events (patient deaths) were reported, with the official release further not providing commentary regarding whether the Grade 5 events were drug-related.
While a full data release from the trial could still provide a win for the regimen, we likely won’t see another update until mid-2024. A data presentation for this interim data is expected to be presented at an upcoming medical conference, likely ESMO 2023 in October, given that the LBA deadline for WCLC 2023 has now passed, and will be key to understanding the true impact of this interim analysis.
Due to the continued failure of second-line regimens, there remains a high unmet need in the setting, especially in patients that have failed prior immune checkpoint inhibitor treatment. AstraZeneca and Daiichi Sankyo had previously guided toward an H2 2023 regulatory filing for the regimen, however, the ambiguity of this initial data release casts uncertainty on whether the FDA will accept an all-comers filing at this time in the absence of OS data; It is more likely that we now won’t see a regulatory filing until OS data is reported next year. While Dato-DXd could still become the first new regimen to market in the 2L setting, a number of other key upcoming readouts including a 2024 readout for Gilead’s own TROP2 ADC Trodelvy, make the 2L NSCLC landscape increasingly competitive.