Astra shifts its dato lung focus again
The approval chances for AstraZeneca and Daiichi’s anti-TROP2 ADC datopotamab deruxtecan in second-line lung cancer already looked questionable; now the partners have pulled their existing filing and shifted to a new niche. Gone is the BLA based on Tropion-Lung01, in metastatic non-squamous NSCLC, on which the FDA had been expected to rule by December. This itself was a narrower use than once hoped, after Tropion-Lung01 failed to show a benefit in squamous disease. The new focus will be second-line EGFR-mutant NSCLC, based on the phase 2 Tropion-Lung05, which found a 44% ORR among this group. Tropion-Lung15 will serve as a confirmatory trial. The partners said the move was informed by feedback from the FDA, presumably following disappointing overall survival data in Tropion-Lung01, reported at World Lung. During a third-quarter media call on Tuesday, Astra noted that EGFR mutations were seen in around 20% of NSCLC; chief executive Pascal Soriot added that the peak sales potential of dato-dxd remained the same, and that the bigger opportunity was first-line lung, where various studies are ongoing. Astra is also awaiting a decision next year in second-line breast cancer, where the Tropion-Breast01 study similarly prevailed on PFS, but not on OS.
Dato-dxd late-stage trials in first-line NSCLC
| Trial | Setting | Regimen | Data expected |
|---|---|---|---|
| Avanzar | No actionable mutations; focus on TROP2 biomarker-positive pts | + Imfinzi + carboplatin vs Keytruda + chemo | H2 2025 |
| Tropion-Lung07 | No actionable mutations; PD-L1 <50% | + Keytruda +/- chemo vs Keytruda + chemo | >2025 |
| Tropion-Lung08 | No actionable mutations; PD-L1 ≥50% | + Keytruda vs Keytruda | >2025 |
| Tropion-Lung10 | No actionable mutations; PD-L1 ≥50%; focus on TROP2 biomarker-positive pts | rilvegostomig +/- dato-dxd vs Keytruda | >2025 |
| Tropion-Lung14 | EGFRm (Ex19del and/or L858R) | + Tagrisso vs Tagrisso | >2025 |
Source: OncologyPipeline & clinicaltrials.gov.
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