Herceptin (trastuzumab)

P1, N=19, Recruiting, Radboud University Medical Center

P2, N=120, Recruiting, ALX Oncology Inc.

Cardioprotection against Anthracycline-induced cardiotoxicity is primarily achieved through lipid-independent mechanisms, including the suppression of inflammasome-mediated injury, modulation of innate immune signaling, attenuation of myocardial fibrosis, and restoration of mitochondrial homeostasis, which are regulated by PCSK9 inhibition. The inhibition of PCSK9 has been demonstrated in preclinical models to enhance anticancer efficacy by reducing chemoresistance and increasing cardiomyocyte viability by 35-88% during anthracycline/trastuzumab exposure.

These findings enable risk stratification before trastuzumab initiation. Future research should validate a predictive model incorporating these factors and assess cardioprotective strategies, thereby translating risk assessment into actionable protocols to optimize cardiac safety without compromising oncologic outcomes.

Chemotherapy was the first-line regimen in 83 of 162 patients (51%), endocrine monotherapy in 55 of 162 (34%), and trastuzumab-pertuzumab-taxane or cyclin-dependent kinase 4 and 6 inhibitor-based regimens in eight of 162 (5%). 87534309); Center for Global Health at the United States-National Cancer Institute at the National Institutes of Health (contract award No. HHSN2612010000871/NO2-PC-2010-00087); Fogarty International Center, NIH, HHS; and Susan G. Komen for the Cure; in Argentina, Instituto Nacional del Cáncer (Ministry of Health), Fundación Argentina de Nanotecnología, Agencia Nacional de Promoción Científica y Tecnológica, CONICET (Ministry of Science, Technology, and Productive Innovation); Brazil, Ministério da Saúde (Ministry of Health); Chile, Instituto de Salud Pública (Public Health Institute) and Ministerio de Salud (Ministry of Health); and Mexico, Consejo Estatal de Ciencia y Tecnología de Jalisco (COECYTJAL) and Universidad de Sonora (University of Sonora).

In vivo, an MMP2/9-cleavable masked anti-TNFα antibody retained efficacy comparable to adalimumab and infliximab in a collagen antibody-induced arthritis model, yet, unlike the reference antibodies, did not measurably reduce survival in a Listeria monocytogenes infection challenge model at the dose tested. This generalized approach was demonstrated across multiple antibodies, enabling efficient protease-dependent conditional activation of trastuzumab (anti-HER2), an anti-IL-1β antibody, and bevacizumab (anti-VEGF). Together, these results established an engineered IGF-II-based masking domain as a versatile, IGF-II receptor-silent platform enabling protease-dependent conditional activation of therapeutic antibodies, with potential to improve safety and expand therapeutic windows.

P1/2, N=42, Not yet recruiting, Duke University | Initiation date: Feb 2026 --> Jul 2026

Conjugation of nanoparticles with Herceptin® (trastuzumab) significantly increased cellular uptake and anticancer activity, especially in clathrin-deficient SK-BR-3 cells that overexpress ERBB2. These findings establish that the easily synthesized PL-MNP-pBIRC5/As-BIRC5 and PL-MNP-pBIRC5/dN-BIRC5 nanodrugs have strong potential to overcome BIRC5- and ABCB1-related drug resistance, representing a broadly applicable strategy against various malignancies. While the size of our nanodrug (~400 nm in hydrodynamic diameter) is compatible with reported effective nanoparticle sizes in some models, the extent to which the enhanced permeability and retention (EPR) effect contributes to tumor accumulation in human cancers remains uncertain and will require validation in more clinically relevant models and imaging modalities.

These results indicate a synergistic interaction between tras tuzumab and blood serum in both groups. We also found significant differences in CI values between healthy donors and breast cancer patients: blood serum samples from patients enhance the effect of trastuzumab to a greater extent.

P2, N=54, Not yet recruiting, National Taiwan University Hospital

P=N/A, N=13, Terminated, University of Washington | Active, not recruiting --> Terminated; Study closed to accrual after meeting grant enrollment goal, prior to reaching protocol accrual goal, due to end of funding.

Failure to correct a vitamin D deficiency was associated with a 1.7-fold higher recurrence risk, although the relationship did not achieve statistical significance. A similar effect size was reported in another retrospective cohort of HER2-positive breast cancer that did achieve statistical significance, and a doubling of pCR rates was seen in two recently completed RCTs in 2025, with benefits particularly seen in the triple-negative and HER2-positive subtypes. Prospective trials evaluating optimized vitamin D repletion in HER2-positive breast cancer are warranted.