Mylotarg (gemtuzumab ozogamicin)

We validated these clinical and molecular findings in an independent validation cohort of 302 NPM1 mut patients enrolled in the acute myeloid leukemia study group (AMLSG) 09-09 clinical trial, which included the administration of all-trans retinoic acid (ATRA) to all patients and a randomization for gemtuzumab ozogamicin. In this cohort, the APL-like immunophenotype was associated with events occurring within the first 15 days but did not influence mortality, likely due to protocol-driven patient selection. Our findings have important clinical implications that warrant the development of studies exploring disease-tailored clinical measures to mitigate the risk of early vascular events, as in current APL management.

P3, N=700, Active, not recruiting, University of Birmingham | Recruiting --> Active, not recruiting

Such inhibition caused cell line-dependent changes in the expression of apoptotic regulators, including BCL-2, MCL-1 and p53 protein, suggesting that cellular context shapes responses to combined treatments. In conclusion, our findings identify BCL-2 and PI3K inhibition as a promising new approach to sensitize AML cells to GO therapy, and highlight the importance of these pathways in determining the cellular response to gemtuzumab ozogamicin.

Fludarabine, cytarabine, and G-CSF-based therapy (FLAG) yields approximately 60% 5-year overall survival (OS) in core-binding factor (CBF) AML, with potential added benefit with gemtuzumab ozogamicin (GO)...We interrogated these factors in 219 frontline patients with CBF-AML (median age 52 years; range 19-80) treated on a phase 2 trial (NCT00801489); 51% received FLAG-GO and 49% FLAG-idarubicin...On multivariate analysis, baseline mutations did not affect OPR or survival, while FLAG-GO favored both. In CBF-AML, FLAG-based therapy possibly attenuates the prognostic impact of concurrent baseline genomics.

P=N/A, N=165, Recruiting, Pfizer | Trial completion date: Apr 2027 --> Jul 2027 | Trial primary completion date: Apr 2027 --> Jul 2027

P4, N=289, Recruiting, Medizinische Hochschule Hannover | N=128 --> 289

P4, N=128, Recruiting, Medizinische Hochschule Hannover | N=52 --> 128

P1, N=32, Not yet recruiting, M.D. Anderson Cancer Center | Initiation date: Dec 2025 --> Dec 2027

P2, N=162, Not yet recruiting, National Cancer Institute (NCI) | Initiation date: Feb 2026 --> Jun 2026

In the in vivo experiments, mice bearing Molm13-Luciferase tumor cells were assigned to different treatment groups and were administered with saline, Gemtuzumab-MMAE, or Clone3HM-MMAE...Clone3HM-MMAE, in particular, demonstrated excellent anti-tumor activity along with a strong safety profile. These results strongly support the further development of targeted therapeutic strategies for AML.

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.

P1, N=26, Completed, Baylor College of Medicine | Active, not recruiting --> Completed