the drug into other populations with less advanced forms of disease as well. Last September, Genentech reported from a study called ‘4450, which showed T-DM1 outperformed the original trastuzumab in a head-to-head study among 137 patients getting their first round of therapy. Genentech is also conducting a pivotal study, called Marianne, which is asking whether a combo of T-DM1 and another new Genentech antibody called pertuzumab could be even more effective in HER2-positive breast cancer patients getting their first round of treatment.
Now with the original trastuzumab, pertuzumab, and T-DM1, Genentech is thinking a lot about how to best tackle HER2-positive breast cancer in its many stages, including the “adjuvant” setting where doctors seek to attack the cancer at an early stage and keep it from coming back.
“About 28,000 patients have been cured in the adjuvant by using Herceptin (trastuzumab),” Berger says. “We’re asking ourselves, ‘Can we further improve on that?”
Beyond the potential implications for this specific subset of breast cancer patients, Genentech’s scientists have been emboldened by their ability to solve the tough technical challenges with creating a new kind of therapy that works like a targeted “smart bomb” against cancer. While Pfizer’s gemtuzumab ozogamicin (Mylotarg) was the first of these antibody-drug conjugates approved by the FDA more than a decade ago, it was linked to significant side effects, was never widely used, and was recently taken off the market. Many researchers struggled to keep the targeted antibody stable and linked together with the toxin, so the toxin could be selectively unleashed on tumors, while largely sparing healthy tissues.
Last August, Seattle Genetics won FDA approval for another one of these antibody-drug conjugate drugs, which showed striking anti-tumor effectiveness for a couple of rare lymphomas. That success, combined with Genentech’s results with T-DM1, have inspired a wave of new companies to attempt to make new and different kinds of these more potent cancer drugs. Genentech alone has 25 of these antibody-drug conjugates at various stages of development, and nine are in clinical trials.
The data that’s being presented today is the kind of thing that has helped set Genentech’s priorities in its R&D pipeline, Berger says. The clinical results are spawning all kinds of new lines of scientific exploration. Suddenly, when good drug targets are identified on cancer cells, scientists will immediately think about making not just “naked antibodies” but also “empowered antibodies” against them. “This is important to us as a company as we believe in ADCs [antibody-drug conjugates] as a platform,” Berger says. “It’s a platform that we believe has the capacity in the mid and long-term to transform a lot of what we do.”
