anvatabart opadotin (JNJ-0683)

Novel agents such as ARX788, patritumab deruxtecan, and Dato-DXd demonstrate promise in overcoming resistance through diversified mechanisms. Real-world data further support a "three-step strategy" involving ADC rechallenge after interim non-ADC therapies, offering a practical, mechanism-informed treatment model. This review provides a framework for precision-guided care in patients with advanced breast cancer and supports ongoing efforts to extend the therapeutic window beyond initial T-DXd benefit.

P2, N=36, Recruiting, Laura Huppert, MD, BA | Not yet recruiting --> Recruiting

Eligible participants were patients (aged 18-75 years) with HER2-positive breast cancer who had received trastuzumab, taxane, and tyrosine kinase inhibitor (TKI) treatment, and also had at least one measurable active brain metastatic lesion (≥1 cm). Future prospective studies incorporating patient-reported outcomes are needed to better capture the clinical benefit of ARX788. National Natural Science Foundation of China; National Key Research and Development Program of China; Shanghai Science and Technology Innovation Action Plan; and Beijing Science and Technology Innovation Medical Development Foundation Key Project.

P2, N=71, Active, not recruiting, Ambrx, Inc. | Recruiting --> Active, not recruiting

Furthermore, we present updated clinical trial data for published HER2-targeted agents and explore ongoing clinical trials examining combinatorial therapies and next-generation HER2-targeted agents such as zongertinib, A166, ARX788, SHRA1811, and others. Given the rapid evolution in this field, our review offers a timely and comprehensive synthesis of the current state and future directions for HER2-altered NSCLC.

Interstitial lung disease (ILD)/pneumonitis and ocular events were observed with ARX788 plus pyrotinib, indicating a distinct safety profile. These findings offer clinical insights into the potential of dual HER2-targeted blockade with an ADC and TKI as an optional neoadjuvant strategy for patients with early or locally advanced HER2-positive breast cancer.

This review explores the application of antibody-drug conjugates (ADCs), such as trastuzumab emtansine (T-DM1), trastuzumab deruxtecan (T-DXd) and sacituzumab govitecan (SG), in treating breast cancer among elderly populations. Emerging ADCs, including datopotamab deruxtecan and ARX-788, show promise but lack extensive geriatric-specific data. While the ADCs offer encouraging results in terms of efficacy and safety, with appropriate dose adjustments, further research is needed to optimize their use in elderly patients with breast cancer.

This phase III trial aimed to compare ARX788, a site-specific, construct-homogeneous antibody-drug conjugate, with lapatinib plus capecitabine in patients with human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer (ABC) who had progressed on one line of trastuzumab based regimen. Six treatment-related deaths occurred, with three cases possibly related to ILD. ARX788 significantly improved PFS compared with LC in patients with HER2-positive ABC with a distinct toxicity profile, supporting it as a potential treatment option.

P2, N=71, Recruiting, Ambrx, Inc. | Trial completion date: Dec 2026 --> Jun 2027 | Trial primary completion date: Jun 2025 --> Dec 2026

P2, N=44, He'nan Cancer Hospital; He'nan Cancer Hospital

P2, N=36, Not yet recruiting, Laura Huppert, MD, BA | Trial completion date: Feb 2028 --> Jun 2028 | Initiation date: Oct 2024 --> Jan 2025 | Trial primary completion date: Feb 2028 --> Jun 2028

The patient was treated with ADCs of ARX-788 for third-line treatment, she had ILD. After treatment of ILD, the patient was treated with ADCs of trastuzumab-DM1 (T-DM1) for fourth-line treatment and she had ILD again...Whether other anti-HER2 ADCs can be tried in the later lines is still being cautious. Whether there is a certain relationship between the side effects and efficacy of ADCs, there is no evidence-based data.