Astra ditches a Duo

AstraZeneca, already facing delays and discontinuations for its TROP2-targeting ADC Datroway, slipped more bad news into its fourth-quarter earnings, this time about its PARP inhibitor Lynparza and its ATR inhibitor ceralasertib.

The company has decided not to pursue regulatory filings for Lynparza plus Imfinzi and Avastin in first-line ovarian cancer, based on the Duo-O trial, which failed for overall survival. Meanwhile, a phase 1/2 solid tumour trial of ceralasertib was discontinued for a lack of efficacy – hot on the heels of last year’s failure of the phase 3 Latify study, which tested an Imfinzi combo in post-PD-(L)1 inhibitor NSCLC.

And a phase 3 NCI-sponsored ceralasertib study in adjuvant NSCLC, called Clear, has been suspended “due to new data”, according to its clinicaltrials.gov listing.

Still in play is an Astra-sponsored phase 2 umbrella post-PD-(L)1 NSCLC study, Hudson, which includes ceralasertib cohorts, both as monotherapy and in combination with Imfinzi. However, hopes for the project’s future cannot now be high.

As for Duo-O, that study hinted at an unexpected way into ovarian cancer for immuno-oncology, effectively by excluding BRCA-positive patients, according to the trial's PFS readout at ASCO in 2023. However, hopes were dashed at last year's ESMO, when overall survival data drew a blank, and now the use won't be pursued.

Datroway delays

Astra also disclosed the discontinuation of the Tropion-Lung12 trial, which tested Datroway plus Astra’s anti-TIGIT x PD-1 MAb rilvegostomig, or rilvegostomig alone, versus chemo in ctDNA-positive stage I NSCLC.

However, this news had already been announced by the group’s partner Daiichi during its own fourth-quarter earnings presentation, along with a delay to the long-awaited Avanzar study. The latter, in first-line NSCLC, relies on an Astra in-house diagnostic to identify patients who might be especially susceptible to treatment with an anti-TROP2 ADC.

During Astra’s fourth-quarter media event the group’s vice-president of oncology R&D, Susan Galbraith, blamed a slowing event rate for the Avanzar delay. This could be good news if Datroway is preventing disease progression and death, but it also means that the same effect might be happening in the control arm.

Readout from two more Datroway trials, Tropion-Lung07 and Tropion-Lung08, in first-line non-squamous NSCLC, has also been pushed back from the first half to the second half of the year.

And, in another delay, Astra has also disclosed that the Saffron study of the Hutchmed-originated cMet inhibitor savolitinib plus Tagrisso in second-line EGFR-mutant NSCLC is now set to yield data in the second half, versus the first half of 2026 previously.

AstraZeneca Q4 2025 oncology discontinuations

Source: OncologyPipeline & company Q4 2025 presentation.