Genentech made its name in cancer by creating targeted antibody drugs that zero in on tumor cells while mostly sparing healthy tissue. Now it’s seeking to compete in the next wave of cancer immunotherapies, which are designed to spark the immune system to attack tumors like a virus.
South San Francisco-based Genentech, a unit of Roche, is releasing results from an early-stage clinical trial today of an experimental antibody designed to hit a target called PD-L1. By aiming for this molecular target, the Genentech antibody is supposed to stop a cloaking mechanism that tumors use to disguise themselves from the immune system. This way, the body’s immune T cells recognize tumors as foreign invaders that should be destroyed like viruses or bacteria.
The drug, code-named MPDL3280A, showed that it was able to shrink tumors by at least half for 29 out of the first 140 patients (21 percent) in a study of cancer patients whose disease had worsened after prior therapies. The Genentech drug appeared to work for many different malignancies, including lung cancer, melanoma, and kidney, colorectal, and gastric cancers. The responses appeared to be long-lasting, although more long-term follow-up will be needed before researchers can say how long the drug might be working.
Like other drugs in this class, the Genentech antibody unleashed the power of the immune system, which can sometimes go too far, damaging healthy tissues. About 39 percent of patients had moderate to severe side effects, including toxicity to the liver, skin, and gut. The results are also still preliminary, so researchers can’t say whether the drug helped patients live longer. A summary of the study has been posted online today by the American Society of Clinical Oncology, as a preview before more detailed results are discussed at ASCO’s annual convention in Chicago.
Still, the results are encouraging enough that Genentech has decided to leap ahead into the final phase of clinical trials with this drug, putting it in the hunt with a number of other major drugmakers. Bristol-Myers Squibb, Merck, and GlaxoSmithKline are all racing to develop what you could call second-generation immunotherapies. Seattle-based Dendreon won FDA approval in 2010 for the first immunotherapy, sipuleucel-T (Provenge), that was shown to extend lives with a minimum of side effects for men with prostate cancer. Bristol-Myers followed that up a year later with another product, ipilimumab (Yervoy), that fights melanoma by releasing a brake on the immune system.
The newer wave of immunotherapies, to be presented this year at ASCO, are homing in on a target called PD-1, in one way or another. Bristol-Myers generated lots of buzz last year with its experimental drug in this category, which appeared to shrink tumors for multiple kinds of cancer. The Genentech antibody is designed to lift the same tumor-cloaking mechanism, but in a different way, because it binds to the PD-L1 ligand instead of directly to the PD-1 protein itself. Genentech hopes that specific form of targeting will make it a safer product, said Chris Bowden, a Genentech vice president of product development for oncology.
“We are impressed with the frequency and duration of the responses in these patients with very difficult-to-treat tumors. So far, almost none of the patients that have had tumor shrinkage have progressed,” said Roy Herbst, the Ensign professor of medicine at Yale Cancer Center and an investigator on the study, in a statement. “This drug is part of an exciting new generation of drugs that unlock the power of the immune system to attack the cancer.”
Mitch Gold, the former chief executive of Dendreon and a board member of the nonprofit Cancer Research Institute in New York, said the data from Genentech’s drug looks encouraging for multiple tumor types. Payers will also want to see if Genentech can increase the response rate in future trials, whether it can select patients most likely to benefit, and whether the drug can extend survival time, to ensure they are getting good value for the money, Gold said.
“If you look at Provenge and first-generation immunotherapies being like a proof of concept, it’s sort of like what Netscape was for the Internet,” Gold said. “We’ve shown immunotherapy is a valuable tool in the fight against cancer. The next-generation compounds are going to look even better. They’ll be like Apple and Google against cancer.”
It’s still far too early to proclaim Genentech is making that kind of advance, based on the data released today. But here’s what is known so far:
—The Genentech antibody appeared to
