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A second dato-dxd/Tagrisso combo

Fresh from taking datopotamab deruxtecan into pivotal development in combination with the anti-PD-1 x TIGIT bispecific rilvegostomig, Daiichi Sankyo/AstraZeneca are starting a phase 3 trial of a dato-dxd combo with Tagrisso. Tropion-Lung15 is to begin in August, according to a just revealed entry, and it’s the second phase 3 to test a dapo-dxd/Tagrisso combo; however, it will do so in a second-line NSCLC setting, in patients progressed on Tagrisso. The Tropion-Lung14 trial, unveiled in April and due to start imminently, concerns a front-line setting aiming simply to beat Tagrisso, where the mPFS benchmark is 17-19 months, according to the Flaura trial or the control arm of Flaura2. For Tropion-Lung15 it’s harder to set a bar because the comparator is chemotherapy, and it’s not obvious how much PFS this would be expected to give once Tagrisso has failed. Effectively, Tropion-Lung15 is seeing whether dato-dxd can rescue such patients, and interestingly the study includes a dato-dxd monotherapy cohort (Tropion-Lung10 includes rilvegostomig monotherapy), though in patients who relapse via an EGFR resistance pathway continued Tagrisso administration would be needed to maintain efficacy. Dato-dxd, an anti-TROP2 ADC, is now in 12 pivotal trials, seven being in NSCLC.


Pivotal trials of datopotamab deruxtecan in lung cancer

TrialSettingActive treatmentControlPrimary endpoint(s)
Tropion-Lung01*2nd-line NSCLCDatopotamab deruxtecanChemoPFS & OS
Tropion-Lung071st-line NSCLCDatopotamab deruxtecan + Keytruda +/- chemoKeytruda + chemoPFS & OS
Tropion-Lung081st-line NSCLCDatopotamab deruxtecan + KeytrudaKeytrudaPFS & OS
Tropion-Lung101st-line, PD-L1≥50%, non-squam NSCLCRilvegostomig +/- datopotamab deruxtecanKeytrudaPFS & OS, in TROP2 expressers
Tropion-Lung141st-line EGFR+ve NSCLCDatopotamab deruxtecan + TagrissoTagrissoPFS
Tropion-Lung152nd-line EGFR+ve NSCLCDatopotamab deruxtecan +/- TagrissoChemoPFS
Avanzar1st-line NSCLCDatopotamab deruxtecan + Imfinzi + chemoKeytruda + chemoPFS & OS

Note: *filed for US approval in non-squamous patients, 20 Dec 2024 PDUFA date. Source: OncologyPipeline.


Molecular Drug Targets