In advanced gastroesophageal adenocarcinoma, biomarker-driven targeted therapy already has Phase III evidence on firm ground: in HERIZON-GEA-01, median PFS was 12.4 months for both zanidatamab+tislelizumab plus chemotherapy and zanidatamab plus chemotherapy, versus 8.1 months for trastuzumab plus chemotherapy (HR 0.63), establishing the HER2 bispecific combination strategy in the first line [11]. The CLDN18.2 space sits further back: CLARITY-Gastric 02, captured in the meeting listings, shows sonesitatug vedotin (Sone-Ve) already being developed in a randomized Phase III with capecitabine ± rilvegostomig [2], indicating this ADC's development is extending toward combinations and earlier lines.
The Second Presidential Symposium of ESMO 2026 reported exactly its later-line pivotal data: CLARITY-Gastric 01 (LBA7), sonesitatug vedotin versus investigator's choice, in second- or later-line (2L+) CLDN18.2-positive advanced/metastatic gastroesophageal carcinoma, with enrollment requiring membranous CLDN18.2 expression in ≥25% of tumor cells at any intensity. The primary endpoint, OS in the 3L+ population (n=355), was 10.0 vs 5.0 months, HR 0.47 (95% CI 0.36–0.62, p<0.001); PFS in that population was 4.1 vs 2.7 months, HR 0.56. Another presidential-session post gave ORR 23 vs 13%, mPFS 4.2 vs 3.8 months, and mOS 10 vs 5 months—OS consistent, though the PFS figures differ. The most frequent adverse events were GI, decreased appetite, and hematologic toxicities, grade 3 or higher events 36.4%, with no new safety signals per the post; the discussion was given by @salahAlBatran, MSK's Yelena Janjigian is a co-author, and the presentation was on October 25 at 5:18 p.m. CET.
The increment here: in the pretreated CLDN18.2-positive gastroesophageal cancer population, this ADC delivered a positive Phase III with OS as the primary endpoint—OS doubled in the 3L+ population (10 vs 5 months, HR 0.47), with ORR 23% vs 13%; the lenient enrollment threshold of ≥25% membranous positivity at any intensity widens coverage, and on-site experts already called it a new option and even a new SOC for 2L+. At the pipeline level, CLARITY-Gastric 02 pushes Sone-Ve forward in combination with capecitabine ± rilvegostomig [2]; with arcotatug tavatecan versus TPC also reported at this meeting as a first interim analysis of a Phase III (LBA77) [3], competition among CLDN18.2 ADCs in previously treated gastric/GEJ adenocarcinoma is already dense.
A caveat: all figures above come from on-site posts rather than the full paper—the two posts disagree on PFS, OS in the ITT 2L+ population was truncated in the post, and key details such as follow-up duration, subgroup analyses, and the ocular and peripheral neuropathy toxicity profile (raised on the spot by an expert) remain undisclosed; no independent coverage on the main site yet for this topic, so conclusions await the full publication and peer review.
