A Novel HER2-Targeted Antibody-Drug Conjugate Offers the Possibility of Clinical Dosing at Trastuzumab-Equivalent Exposure Levels
Summary: Trastuzumab and the related antibody-drug conjugate (ADC), ado-trastuzumab emtansine (T-DM1), have treatment indications in both early-stage and metastatic settings for HER2+ breast cancer. T-DM1 retains the antibody functionalities of trastuzumab and adds the potency of a cytotoxic payload. Interestingly, in the clinic, T-DM1 cannot always replace the use of trastuzumab plus chemotherapy given together as single agents. This may be due to the limited systemic exposure achieved by T-DM1 relative to trastuzumab because of toxicity-related dosing constraints on the ADC. In this publication, Catalent scientists demonstrate that a trastuzumab-based ADC made using SMARTag(R) technology displays superior in vivo efficacy and equal or better tolerability to T-DM1 at twice the antibody dose. The data suggest that the SMARTag(R) ADC may enable clinical dosing at trastuzumab-equivalent exposure levels, combining the functions of both the antibody and the payload in one drug and potentially improving patient outcomes.