Astra’s Claudin reckoning approaches

AstraZeneca could soon be taking on Astellas in the field of Claudin18.2. The UK company will report pivotal data with its ADC sonesitatug vedotin in the first half, and will hope that its asset could expand the market currently addressed by Astellas’s Vyloy.

Vyloy, a naked MAb, is only indicated for gastric cancer patients with 75% or higher Claudin18.2 expression. It’s hoped that ADCs could address patients with lower levels; to this end, Astra is enrolling ≥25% expressers in its upcoming phase 3 study, Clarity-Gastric01.

A look at OncologyPipeline shows that, while there are plenty of Chinese late-stage projects, sone-V is the only asset in a phase 3 global trial, at least for now. Still, there is reason for caution: Astra’s project uses an auristatin payload – like LaNova’s tecotabart vedotin and CSPC’s SYSA1801, both of which were abandoned by their western partners, Bristol Myers Squibb and Elevation Oncology respectively. 

Claudin18.2-targeting ADCs in phase 3

Note: *phase 1/3. Source: OncologyPipeline.

As well as enrolling ≥25% expressers, Clarity-Gastric01 is focused on HER2-negative gastric or gastroesophageal junction (GEJ) patients who received at least one prior therapy line, including platinum-fluoropyrimidine chemo. Notably, patients were permitted to have previously received a naked Claudin18.2-targeting MAb such as Vyloy, but not another Claudin18.2-targeting ADC, or Car-T.

The study initially tested two undisclosed doses of sone-V; one of these arms was closed for enrolment, with a 2.2mg/kg dose taken forward. This will be compared against investigator’s choice of therapy, including Cyramza, docetaxel or Lonsurf.

The co-primary endpoints are progression-free survival in the intent-to-treat population, and overall survival in third-line-plus patients. Secondary endpoints include OS in the overall population and PFS in third-line-plus subjects.

Vyloy is approved, in combination with chemo, for first-line, HER2-negative, Claudin18.2-positive (≥75%) gastric and GEJ cancers, based on the Spotlight (plus mFolfox6) and Glow (plus Capox) studies. These found median PFS of 10.6 and 8.2 months respectively (versus 8.7 and 6.8 months respectively with control).

Chinese players

In the front line, a Chinese phase 3 study of sone-V is also ongoing: Clarity-Gastric02. That trial evaluates a combination with fluoropyrimidine, with or without Astra’s anti-TIGIT x PD-1 MAb rilvegostomig; the Claudin18.2 expression cutoff isn’t given in the China drug trials database entry. 

Astra licensed sone-V from KYM Biosciences, a joint venture between Keymed and Lepu, in 2023 for $63m up front.

As for the competition, Takeda’s shot here, arcotatug tavatecan, comes via its $1.2bn deal with Innovent last October; meanwhile, Astellas licensed XNW27011, now known as ASP546C, from Evopoint for $130m up front during last year’s ASCO meeting. Both of these assets use a more fashionable topoisomerase 1 inhibitor payload; Takeda has disclosed plans to start global phase 3s of its asset.

There’s been less positive news for auristatin-based projects: it emerged in 2024 that Bristol had walked away from LaNova’s tecotabart vedotin, which is about to go into a new pivotal Chinese trial in first-line gastric cancers. And Elevation last year ditched CSPC’s EO-3021 following a disappointing clinical update. Astra will be hoping for better results with sone-V.