Pivotal Claudin18.2 candidates keep coming

Despite big pharma cooling on Claudin18.2 there’s still plenty of activity in this space, with new listings on clinicaltrials.gov revealing two new imminent phase 3 studies.

These involve LaNova’s ADC tecotabart vedotin, which was ditched by Bristol Myers Squibb several years ago, and FutureGen’s naked MAb FG-M108. Both were already in pivotal trials, so the latest listings cement their developers’ commitment to this target.

Tecotabart vedotin 

Bristol inherited rights to tecota-V through its $4.1bn takeover of Turning Point Therapeutics in 2022; however, in 2024 it emerged that the big pharma had walked away from the asset.

This hasn’t stopped LaNova – now part of Sino Biopharmaceutical – from pressing on. In 2024 the company started a Chinese pivotal trial in third-line Claudin18.2-positive gastric and gastroesophageal junction (GEJ) cancers; this is set to complete this year, and could support a local filing.

Meanwhile, the new Chinese phase 3 is slated to begin in March in first-line, HER2-negative, Claudin18.2-positive gastric and GEJ cancers. For the purposes of the trial, Claudin18.2 positivity is defined as 25% or greater expression.

The study will test tecota-V plus BeOne’s anti-PD-1 MAb Tevimbra, versus Tevimbra plus chemo, with a primary endpoint of progression-free survival, in PD-L1-positive (≥1%) and Claudin18.2 high expressers (≥75%), and in all comers.

This could be relevant because the only approved Claudin18.2-targeting therapy, in the US and China, is Astellas’s naked MAb Vyloy – and that's only indicated for gastric or GEJ cancer patients with 75% or higher Claudin18.2 expression.

Therefore companies, including Astellas itself, are hoping to address more patients with other modalities such as ADCs and T-cell engagers.

There are currently eight Claudin18.2-targeting ADCs in phase 3 development, according to OncologyPipeline. Other players here include Takeda, which last year licensed arcotatug tavatecan from Innovent; Astellas, whose ASP546C came from Evopoint; and AstraZeneca with the Keymed-originated sonesitatug vedotin. The last project is set to yield phase 3 data this half from the Clarity-Gastric01 trial, in second-line gastric cancer patients with 25% or higher Claudin18.2 expression.

Still, Bristol isn’t the only one to have exited this space: Merck & Co also handed SKB315 back to Kelun in 2024.

FG-M108

Meanwhile, FutureGen’s MAb FG-M108 is set to go into a Chinese phase 3 later this month in first-line pancreatic cancer that’s Claudin18.2-positive (≥40% expression). The project will be combined with Abraxane plus chemo, versus Abraxane plus chemo, with a primary endpoint of overall survival.

An earlier pivotal trial of the project is ongoing in first-line gastric and GEJ cancers that are HER2-negative, Claudin18.2-positive, and have PD-L1 expression of less than 5%. The definition of Claudin18.2-positivity isn’t given; that study is primarily measuring PFS, with a primary completion date of January 2027.

A look at OncologyPipeline shows ADCs as the most popular modality for late-stage Claudin18.2 development, with MAbs some way behind. With plenty of competition, developers of these projects will have to work hard to stand out.

Summary of Claudin18.2-targeting projects in late-stage development

Note: industry-sponsored projects only. Source: OncologyPipeline.