arcotatug tavatecan (IBI-343)

P1, N=470, Recruiting, Innovent Biologics (Suzhou) Co. Ltd. | Trial completion date: Dec 2025 --> Dec 2027 | Trial primary completion date: Dec 2025 --> Jun 2027

Enfortumab vedotin is an NECTIN4-targeting antibody-drug conjugate that is approved for the treatment of urothelial cancer, whereas other ADCs or derivatives that target NECTIN4, such as bulumtatug fuvedotin, SHR-A2102 and zelenectide pevedotin, are being studied in randomized phase III clinical trials. In contrast, arcotatug tavatecan, garetatug rezetecan, sonesitatug vedotin and tecotabart vedotin are anti-CLDN18.2 ADCs in phase III clinical trials for the treatment of CLDN18.2-positive gastric or gastroesophageal junction adenocarcinomas, and raludotatug deruxtecan is an anti-CDH6 ADC in a phase II/III clinical trial for the treatment of platinum-resistant ovarian cancer. ADCs that target cell-cell adhesion molecules are a rapidly emerging class of cancer therapeutics, and bispecific ADCs and longitudinal companion diagnostics are emerging to further improve the clinical benefits of conventional ADCs.

P2, N=64, Recruiting, Zhejiang University | Not yet recruiting --> Recruiting | Initiation date: Jan 2025 --> Apr 2025

P3, N=450, Recruiting, Innovent Biologics (Suzhou) Co. Ltd. | Enrolling by invitation --> Recruiting

P3, N=201, Recruiting, Innovent Biologics (Suzhou) Co. Ltd. | Not yet recruiting --> Recruiting

IBI343 was well tolerated, with a manageable safety profile and promising efficacy in G/GEJ adenocarcinoma. Further research is required to understand optimal sequencing, and biomarker-informed combination therapy, in G/GEJ tumors given the development of multiple therapies targeting CLDN18.2 in addition to human epidermal growth factor receptor 2 and programmed cell death 1 ligand 1.ClinicalTrials.gov registration: NCT05458219 .

P3, N=201, Not yet recruiting, Innovent Biologics (Suzhou) Co. Ltd.

P1/2, N=55, Recruiting, Ruijin Hospital

P2, N=64, Not yet recruiting, Zhejiang University

P1, N=470, Recruiting, Innovent Biologics (Suzhou) Co. Ltd. | N=210 --> 470 | Trial completion date: Oct 2024 --> Dec 2025 | Trial primary completion date: May 2024 --> Dec 2025

The human/humanized anti‑CLDN18.2 mAb osemitamab, and ADCs AZD0901, IBI343 and LM‑302, with single‑agent ORRs of 28‑60%, have been tested in phase III clinical trials. In addition, bsAbs, CAR T cells and their derivatives targeting CLDN4, 6 or 18.2 are in phase I and/or II clinical trials. AZD0901, IBI343, zolbetuximab and the anti‑CLDN1 mAb ALE.C04 have been granted fast track designation or priority review designation by the US Food and Drug Administration.

At the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, the final results of the phase 3 SPOTLIGHT trial were presented, demonstrating a significant survival benefit from the addition of the CLDN18.2-specific antibody zolbetuximab to chemotherapy in the first-line treatment of advanced gastroesophageal adenocarcinomas with ≥ 75% CLDN18.2 expression...In addition, several early-phase trials presented at ASCO 2024 investigate other CLDN18.2-targeting approaches in CLDN18.2-positive refractory advanced solid tumors, including the CLDN18.2-targeting antibody-drug conjugates LM-302 and IBI343, the bispecific anti-CLDN18.2/CD3 antibody IBI38, and the chimeric antigen receptor T cell therapy satricabtagene autoleucel. These novel approaches could potentially expand the benefit of CLDN18.2-targeting therapies to a broader range of tumor types and to tumors expressing lower levels of CLDN18.2.