World’s First CLDN18.2 ADC Submits NDA Following Phase 3 Gastric Cancer Win
On June 4, 2026, Innovent Biologics announced that its investigational claudin-18.2 (CLDN18.2) targeted antibody-drug conjugate (ADC), IBI343 (also known as arcotatug tavatecan or TAK-921), met its primary endpoint of progression-free survival (PFS) in the Phase 3 MarsLight-11 clinical trial. Following the positive readout, China's National Medical Products Administration (NMPA) accepted a New Drug Application (NDA) for IBI343 under priority review, making it the first CLDN18.2-directed ADC in the world to reach regulatory review.
Trial Design and Efficacy Results
The randomized, multi-center Phase 3 MarsLight-11 study enrolled 464 patients in China and Japan with locally advanced unresectable or metastatic CLDN18.2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma. All enrolled patients had progressed after receiving at least two prior lines of systemic therapy.
At a pre-specified interim analysis, IBI343 demonstrated a statistically significant and clinically meaningful improvement in PFS compared to investigator-selected chemotherapy. While Innovent has withheld specific hazard ratios and median PFS numbers for presentation at an upcoming medical congress, investigators reported excellent efficacy and a favorable safety profile. Notably, IBI343 showed a very low rate of gastrointestinal-related toxicities, which have historically plagued other therapies targeting transmembrane proteins like Claudin-18.2.
"At the first interim analysis, progression-free survival (PFS) was significantly longer on IBI343 than on investigator-selected control therapies, which included chemotherapy drugs... China’s National Medical Products Administration has accepted IBI343 for priority review. The filing is the first time a CLDN18.2-directed ADC has begun regulatory review." — Nick Paul Taylor, Fierce Biotech
Mechanism and Commercial Significance
IBI343 is designed to selectively bind to CLDN18.2-expressing tumor cells, internalize, and release a highly potent cytotoxic exatecan payload (a topoisomerase I inhibitor) to induce cell death.
While Astellas Pharma secured the first FDA approval for a CLDN18.2-targeted therapy in 2024 with its monoclonal antibody Vyloy (zolbetuximab), ADCs like IBI343 represent a more potent, next-generation modality. The therapeutic class has attracted intense pharmaceutical interest:
- The Takeda Deal: In 2025, Takeda Pharmaceuticals paid Innovent $1.2 billion in an upfront and milestone-heavy agreement to secure exclusive development and commercialization rights for IBI343 outside of Greater China (where Innovent retains sole rights).
- Competitive Landscape: Major pharmaceutical developers, including AstraZeneca, Astellas, and Merck & Co., are actively chasing CLDN18.2-targeted ADCs and bispecifics, though Innovent currently leads the clinical race to market.
Innovent is also evaluating IBI343 in ongoing clinical trials for first-line gastric cancer and pancreatic cancer.