The potential of ADCs was affirmed earlier this year when Roche's Genentech received FDA approval for Kadcyla (ado-trastuzumab emtansine or T-DM1) for treating HER2-positive metastatic breast cancer (mBC). The drug combines trastuzumab (Herceptin), which targets human epidermal growth factor receptor 2 (HER2) receptors with a maytansine derivative DM1, a small-molecule cytotoxin that binds to tubulin to prevent microtubule formation, through a stable thioether linker (4-[N-maleimidomethyl] cyclohexane-1-carboxylate) (1–3). Roche/Genentech has more than 25 ADCs in development, with eight ADCs in Phase I or Phase II studies for different types of cancer.
Pfizer suffered another setback in its ADC development program earlier this year, when in May, it discontinued a Phase III study for one of its investigational ADCs, inotuzumab ozogamicin, for treating non-Hodgkin lymphoma. The drug continues to be evaluated as a treatment in adult acute lymphoblastic leukemia. Inotuzumab ozogamicin was originally developed by Celltech (now UCB) before Pfizer acquired all manufacturing and development rights.
Pfizer, like other pharmaceutical companies, is partnering with smaller biopharmaceutical companies to advance ADCs. In June 2013, Pfizer formed a global strategic collaboration, worth up to $635 million, with CytomX to develop and commercialize multiple CytomX Probody Drug Conjugates (PDCs), propertiary ADCs of CytomX. Pfizer has exclusive rights to pursue development and commercialization of select PDCs. The companies will work together on preclinical research. Pfizer is responsible for development and potential commercialization of any selected PDCs with CytomX eligible to receive upfront, research, and preclinical milestone payments as well as potential tiered royalties.