Kadcyla (ado-trastuzumab emtansine)

P=N/A, N=10, Active, not recruiting, City of Hope Medical Center | Trial completion date: Oct 2025 --> Sep 2026

DS-8201 showed significantly better efficacy and similar overall safety compared to TPC in patients with T-DM1-pretreated HER2-positive advanced breast cancer, supporting its use as a treatment option in this setting.

For example, a PBAP-HER2 construct synergized with Herceptin and Kadcyla to eliminate human epidermal growth factor receptor 2 (HER2)-negative, PD-L1 positive cells. This work represents an innovative strategy for enhancing PD-L1-targeted therapies by leveraging pre-existing antibodies induced by vaccination or natural viral infections, alongside commercially available antibody-based therapies. Given the broad expression of PD-L1 across various solid tumors and hematologic malignancies, our strategy holds promise as a potentially widely applicable platform for diverse PD-L1-positive patient populations.

P=N/A, N=250, Recruiting, Fudan University

The patient subsequently received adjuvant chest wall and nodal region radiotherapy plus trastuzumab-emtansine (T-DM1). This case underscores the value of personalized, multidisciplinary management in PrBC, particularly in patients with high-risk biologic features and advanced nodal disease. Integrating clinical judgment, genomic tools, and adaptive strategies, while accounting for gestational limitations, can optimize oncologic outcomes without compromising fetal safety.

First-generation ADCs, such as Gemtuzumab ozogamicin, demonstrated the proof of concept but suffered from high immunogenicity, poor selectivity, and heterogeneous drug-antibody ratios. Second-generation ADCs introduced stable linkers and humanized antibodies, exemplified by Ado-trastuzumab emtansine (T-DM1), which targets the HER2 receptor in breast cancer...Third-generation ADCs, including Trastuzumab deruxtecan and Sacituzumab govitecan, incorporate site-specific conjugation, higher drug-to-antibody ratios, and potent payloads capable of inducing bystander killing even in tumors with low antigen expression...In conclusion, ADCs exemplify the convergence of molecular biology, immunology, and medicinal chemistry in the pursuit of precision oncology. Their progressive evolution from concept to clinic not only validates Ehrlich's century-old vision but also heralds a new therapeutic era in which cancer treatment achieves unprecedented specificity, efficacy, and improvement in patient outcomes.

P=N/A, N=20, Completed, Zhejiang Cancer Hospital; Zhejiang Cancer Hospital

P2, N=56, Recruiting, Sun Yat-sen Memorial Hospital, Sun Yat-sen University; Sun Yat-sen Memorial Hospital, Sun Yat-sen University

Trastuzumab first established HER2-targeted therapy in gastric cancer, but the failure of trastuzumab emtansine (T-DM1) led to a decade-long stagnation until the advent of trastuzumab deruxtecan (T-DXd), which demonstrated robust clinical activity and defined a new standard of care. While bevacizumab failed to improve survival, the anti-VEGFR2 antibody ramucirumab emerged as an effective second-line therapy. Immune checkpoint inhibitors, including nivolumab and pembrolizumab, have been incorporated into first-line treatment for PD-L1-positive disease based on landmark trials such as CheckMate 649 and KEYNOTE-811. More recently, the CLDN18.2-targeted antibody zolbetuximab has expanded therapeutic options for biomarker-selected patients. Concurrently, a diverse pipeline of immune-based strategies-such as TROP2-directed ADCs, bispecific antibodies, and CAR-T cell therapies-is undergoing active clinical development. Together, advances in biomarker-driven antibody therapeutics are accelerating personalized cancer care and improving clinical outcomes in patients with gastric cancer.

The study was developed at the Cancer Institute of the State of São Paulo (ICESP) according to the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) recommendations.ResultsIt was possible to obtain a ranking of the 8 alternatives: the first, second and third position were respectively: neoadjuvant treatment without anthracycline and anti-HER2 therapy with only trastuzumab followed by adjuvant trastuzumab (global value 0.739); neoadjuvant treatment with anthracycline and anti-HER2 trastuzumab alone followed by adjuvant trastuzumab (global value 0.717) and neoadjuvant treament with anthracycline plus trastuzumab alone or double anti-HER2 blockade with trastuzumab and pertuzumab, followed by adjuvant T-DM1 (global value 0.697). The criteria that received the greatest weight from stakeholders were in descending order: disease-free survival, cost, severity of the disease, adverse reactions and overall survival.ConclusionMCDA made it possible to compare treatment alternatives for non-metastatic, HER2+, HR + breast cancer, with the most innovative technology T-DM1 appearing fourth.

Overall, the probability of G2P+ in patients receiving radiotherapy for HER2+ or TN BC is low. However, concurrent T-DM1 and radiotherapy was associated with significantly higher rates of pneumonitis than previously reported, suggesting a cautionary approach when combining the two therapies.

P2, N=140, Completed, Dana-Farber Cancer Institute | Active, not recruiting --> Completed