More warnings signs for ATR inhibition
Synthetic lethality is a hot topic in oncology, but the shine might be coming off one of the approaches here, ATR inhibition. Yesterday Bayer discontinued its contender elimusertib, swiftly followed by AstraZeneca today scrapping a trial of its ATR blocker ceralasertib. Importantly, development of ceralasertib continues; indeed, this is the most advanced ATR project. But smaller groups like Aprea and Artios might be watching Astra’s next moves nervously. Other big companies taking a punt on ATR inhibition include Merck KGaA, which has switched focus from berzosertib to tuvusertib, and Roche, which licensed camonsertib from Repare for $125m up front last year. Camonsertib monotherapy has failed to impress, but at the time of the deal some analysts suggested that combination with PARP inhibitors could provide a way forward – notably, Impact Therapeutics is also looking at its ATR blocker, IMP9064, with a PARP. Other combinations are in play, and Repare reported data at the recent Triple meeting on a pairing of camonsertib and its PKMYT1 inhibitor lunresertib – which proved difficult to interpret.
ATR inhibitors in clinical development
Project | Company | Note |
---|---|---|
Phase 3 | ||
Ceralasertib | AstraZeneca | Ph3 Latify + Imfinzi in post-IO NSCLC continues; ph2 Monette + Imfinzi post-IO melanoma discontinued for futility Nov 2023 |
Phase 1/2 | ||
ATRN-119 | Aprea Therapeutics (via Atrin) | First data from ph1/2 in solid tumours at AACR-NCI-EORTC Oct 2023 |
ART0380 | Artios Pharma | First data from ph1/2 +/- gemcitabine/irinotecan in solid tumours at ESMO 2023 |
IMP9064 | Impact Therapeutics | First data from ph1/2 +/- senaparib in solid tumours at ESMO 2023 |
Camonsertib | Roche (licensed from Repare) | Ph1/2 in solid tumours completes Jan 2024 |
TCC1727 | F-star Therapeutics | Ph1/2 in solid tumours completes Mar 2025 |
SC0245 | BioCity Biopharma | Ph1/2 + irinotecan in SCLC completes Sep 2025 |
Tuvusertib | Merck KGaA | Ph1/2 DDRiver NSCLC 322 + Libtayo post-IO completes Aug 2026 |
Phase 1 | ||
ATG-018 | Antengene Corporation | Ph1 Atrium in solid tumours & haematological cancers completes Mar 2024 |
HRS2398 | Jiangsu HengRui | Ph1 recruiting |
Discontinued | ||
Elimusertib | Bayer | Discontinued Nov 2023 |
Berzosertib | Merck KGaA | Ph2 DDRiver SCLC 250 discontinued Jun 2022 |
Source: OncologyPipeline.
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