Aidixi (disitamab vedotin)

P3, N=412, Active, not recruiting, Seagen, a wholly owned subsidiary of Pfizer | Trial primary completion date: Jun 2026 --> Jan 2027

A cross-tumor perspective contrasts GC/GEJ testing and biology with the breast cancer paradigm and summarizes the importance of HER2-low expression in non-gastric malignancies. Finally, we discuss the therapeutic strategies in HER2-low GC/GEJ and highlight key safety and monitoring considerations for HER2-directed ADCs.

P2, N=30, Recruiting, Shanxi Province Cancer Hospital

DS-8201 demonstrates potential as one of the effective salvage therapies following RC48 failure in HER2 altered solid tumors, showing significantly better disease control and a distinct, manageable toxicity profile. These findings highlight the importance of selecting personalized ADCs based on molecular subtypes and toxicity factors and provide a basis for future, larger-scale prospective studies.

In the real-world setting, RC48 shows some clinical efficacy and a manageable safety profile in patients with HER2-expressing advanced gastric cancer. These findings provide useful information for clinical practice.

After initial treatment with transurethral resection of the bladder tumor (TURBT), the patient underwent regular bladder instillations of epirubicin...Due to the patient's renal impairment (baseline creatinine 107.8 µmol/L, glomerular filtration rate (GFR) 79.19 mL/min/1.73m2) and human epidermal growth factor receptor 2 (HER2) overexpression (2+), the decision was made to employ an antibody-drug conjugate (ADC) targeting HER2 (disitamab vedotin, 120 mg intravenously). The report outlines the patient's background, the progression of his disease, the decision-making process behind the use of ADC therapy, and the subsequent response to treatment. The successful control of the disease with ADC therapy in this complex patient population highlights its potential as an effective and less toxic alternative to conventional chemotherapy, particularly in patients with recurrent bladder cancer after renal transplantation.

Time-dependent ROC analysis showed an AUC of 76.3% at 2 years, and decision curve analysis suggested potential clinical utility. These findings indicate that miR-145 may serve as a candidate prognostic biomarker for risk stratification in RC48-treated la/mUC.

Therapeutic agents such as trastuzumab deruxtecan and disitamab vedotin are currently approved ADCs in HER2-overexpressing GI cancers, while multiple investigational ADCs targeting novel antigens, including Claudin 18.2, Claudin 6, B7-H3, c-MET, TROP2, and EGFR, are being evaluated in ongoing clinical trials. Innovative designs-such as biparatopic and bispecific formats, dual or multipayload strategies, and the integration of novel cytotoxic modalities like radiotherapeutic agents-are under active development to address resistance mechanisms, optimize payload delivery, and minimize off-target toxicity. This review summarizes the structural components, mechanisms of action, approved agents, and evolving clinical pipeline of ADCs in GI cancers, highlighting both current challenges and emerging strategies aimed at expanding their therapeutic potential.

P2/3, N=240, Not yet recruiting, West China Hospital

As the first China-developed anti-HER2 antibody-drug conjugate (ADC), RC-48 may provide clinically meaningful benefit in selected patients with HER2-low metastatic breast cancer. This case also underscores the importance of reassessing HER2 status during disease evolution and supports the potential value of ADC-based therapy in later-line treatment.

P2/3, N=80, Recruiting, RemeGen Co., Ltd. | Not yet recruiting --> Recruiting | N=700 --> 80 | Trial primary completion date: Dec 2027 --> May 2027

P2, N=49, Not yet recruiting, RenJi Hospital