Claudin18.2 ADC Race Intensifies as AstraZeneca Prepares Pivotal Data While Chinese Competitors Advance
核心洞察
AstraZeneca's sonesitatug vedotin (搜索) is set to report pivotal phase 3 data in the first half of 2026 from the global Clarity-Gastric01 trial, testing the ADC in second-line gastric cancer (搜索) patients with ≥25% Claudin18.2 (搜索) expression.
Two new phase 3 studies are launching in March 2025, including LaNova (搜索)'s tecotabart vedotin in first-line gastric cancer (搜索) and FutureGen (搜索)'s FG-M108 monoclonal antibody in first-line pancreatic cancer (搜索).
Eight Claudin18.2 (搜索)-targeting ADCs are currently in phase 3 development, with companies seeking to expand beyond Astellas's Vyloy, which is only approved for patients with ≥75% Claudin18.2 expression.
The race to develop next-generation Claudin18.2 (搜索)-targeting therapies is intensifying, with AstraZeneca poised to report pivotal data from its antibody-drug conjugate (ADC) sonesitatug vedotin (搜索) in the first half of 2026, while multiple Chinese competitors advance their own programs despite recent Western pharmaceutical exits from the space.
AstraZeneca's sonesitatug vedotin (搜索) represents the only Claudin18.2 (搜索)-targeting ADC currently in a global phase 3 trial. The company's Clarity-Gastric01 study is evaluating the therapy at a 2.2mg/kg dose in HER2-negative gastric or gastroesophageal junction cancer (搜索) patients with at least 25% Claudin18.2 expression who have received at least one prior therapy line, including platinum-fluoropyrimidine chemotherapy.
The trial's co-primary endpoints are progression-free survival in the intent-to-treat population and overall survival in third-line-plus patients. Secondary endpoints include overall survival in the overall population and progression-free survival in third-line-plus subjects. Notably, patients were permitted to have previously received naked Claudin18.2 (搜索)-targeting monoclonal antibodies such as Astellas's Vyloy, but not other Claudin18.2-targeting ADCs or CAR-T therapies.
Expanding Beyond Current Treatment Options
The clinical development strategy reflects an effort to expand beyond the current market addressed by Vyloy, the only approved Claudin18.2 (搜索)-targeting therapy in the US and China. Vyloy is indicated only for gastric or gastroesophageal junction cancer (搜索) patients with 75% or higher Claudin18.2 expression, based on data from the Spotlight and Glow studies that demonstrated median progression-free survival of 10.6 and 8.2 months respectively.
By targeting patients with 25% or higher expression levels, sonesitatug vedotin (搜索) and other ADCs in development aim to address a broader patient population. AstraZeneca licensed the asset from KYM Biosciences, a joint venture between Keymed (搜索) and Lepu, in 2023 for $63 million upfront.
New Phase 3 Launches Signal Continued Investment
Despite cooling interest from some major pharmaceutical companies, new phase 3 studies are set to launch in March 2025. LaNova (搜索)'s tecotabart vedotin, now part of Sino Biopharmaceutical, will begin a Chinese phase 3 trial in first-line, HER2-negative, Claudin18.2 (搜索)-positive gastric and gastroesophageal junction cancers. The study defines Claudin18.2 positivity as 25% or greater expression and will test the ADC plus BeOne's anti-PD-1 monoclonal antibody Tevimbra versus Tevimbra plus chemotherapy.
The trial's primary endpoint is progression-free survival in PD-L1-positive (≥1%) and Claudin18.2 (搜索) high expressers (≥75%), as well as in all comers. This follows LaNova (搜索)'s ongoing Chinese pivotal trial in third-line Claudin18.2-positive gastric and gastroesophageal junction cancers, which is set to complete in 2025 and could support a local filing.
FutureGen (搜索)'s monoclonal antibody FG-M108 is also launching a Chinese phase 3 study in first-line pancreatic cancer (搜索) with at least 40% Claudin18.2 (搜索) expression. The project will be combined with Abraxane plus chemotherapy versus Abraxane plus chemotherapy alone, with overall survival as the primary endpoint.
Western Pharmaceutical Exits Create Opportunities
The continued development comes despite several high-profile exits from Western pharmaceutical companies. Bristol Myers Squibb (搜索) walked away from tecotabart vedotin in 2024, despite inheriting rights through its $4.1 billion takeover of Turning Point Therapeutics in 2022. Similarly, Merck & Co handed SKB315 back to Kelun in 2024, and Elevation Oncology discontinued development of CSPC's SYSA1801 in March 2025.
These departures have left the field increasingly dominated by Chinese developers and licensing partnerships. According to OncologyPipeline data, eight Claudin18.2 (搜索)-targeting ADCs are currently in phase 3 development, with ADCs representing the most popular modality for late-stage development.
Competitive Landscape and Payload Strategies
The competitive landscape reveals different strategic approaches to payload selection. AstraZeneca's sonesitatug vedotin (搜索) uses an auristatin payload, similar to LaNova (搜索)'s tecotabart vedotin and CSPC's SYSA1801, both of which were abandoned by their Western partners. In contrast, newer entrants are employing topoisomerase 1 inhibitor payloads, including Takeda (搜索)'s arcotatug tavatecan (搜索), licensed from Innovent (搜索) for $1.2 billion, and Astellas's ASP546C (搜索), acquired from Evopoint for $130 million upfront.
Takeda (搜索) has disclosed plans to initiate global phase 3 studies of arcotatug tavatecan (搜索), while multiple Chinese companies including Jiangsu HengRui, Junshi Biosciences, and others are advancing their own ADC programs through pivotal trials scheduled to complete between 2026 and 2027.
The diverse pipeline reflects ongoing confidence in Claudin18.2 (搜索) as a therapeutic target, despite the challenges faced by some early programs. With AstraZeneca's global data expected in the first half of 2026 and multiple Chinese programs advancing simultaneously, the next two years will be critical in determining which approaches can successfully expand treatment options beyond the current standard established by Vyloy.