ERBB2 amplification could become a novel target in mUC, although the magnitude of clinical benefit remains to be clarified. To this regard, novel ADCs are the most promising strategy. ERBB2 mutations are still at very early stage of clinical study.

almost 3 years ago

Review • Journal • IO biomarker

HER-2 (Human epidermal growth factor receptor 2)

HER-2 amplification • HER-2 mutation

Kadcyla (ado-trastuzumab emtansine) • Enhertu (fam-trastuzumab deruxtecan-nxki) • Aidixi (disitamab vedotin) • Jivadco (trastuzumab duocarmazine) • ADCT-502

over4years

The role of specific ATP-binding cassette transporters in the acquired resistance to pyrrolobenzodiazepine dimer-containing antibody-drug conjugates. (PubMed, Mol Cancer Ther)

These include ADCT-301 (camidanlumab tesirine) and ADCT-402 (loncastuximab tesirine) in pivotal Phase 2 trials that contain the payload tesirine which releases the PBD dimer warhead SG3199...The level of resistance achieved was ~3000-fold for ADCT-301 and 3-fold for SG3199 in Karpas-299, and 8-fold for ADCT-502 and 4-fold for SG3199 in NCI-N87...These data show that acquired resistance to PBD-ADCs and SG3199 can involve specific ATP-binding cassette (ABC) drug transporters. This has clinical implications as potential biomarkers of resistance and for the rational design of drug combinations.

over 4 years ago

Preclinical • Journal

HER-2 (Human epidermal growth factor receptor 2) • ABCB1 (ATP Binding Cassette Subfamily B Member 1) • IL2RA (Interleukin 2 receptor, alpha) • ABCC2 (ATP Binding Cassette Subfamily C Member 2)

Zynlonta (loncastuximab tesirine-lpyl) • camidanlumab tesirine (ADCT-301) • ADCT-502