Merck wasn’t the first company to develop targeted antibody drugs 15 years ago, and wasn’t first to show immunotherapy could work against cancer a couple years ago. But the giant drugmaker has put itself in the small group of companies bringing forward a wave of new treatments that stimulate the immune system to fight cancer cells like a virus.
The Whitehouse Station, NJ-based drugmaker (NYSE: MRK) is reporting today that a high dose of its experimental immune-booster against cancer, lambrolizumab, was able to shrink tumors in more than half of patients with a deadly form of skin cancer that had spread after prior treatment. The drug’s effect appeared to be long-lasting, possibly because it “teaches” the immune system to seek and destroy cancer cells. About 13 percent of patients reported a moderate to severe side effect, such as rash, fatigue, or liver toxicity.
The results, from a study of 135 patients, are being published online in the New England Journal of Medicine, and being presented at the American Society of Clinical Oncology’s annual meeting by Antoni Ribas, the director of the Tumor Immunology Program at the Jonsson Comprehensive Cancer Center at UCLA. The findings put Merck in the mix with companies like Bristol-Myers Squibb and Roche/Genentech, who are racing ahead with drugs that all seek to work by inhibiting a cloaking mechanism that tumors use to disguise themselves from the immune system.
All three companies are jockeying for attention at the big ASCO meeting this weekend, where researchers are buzzing about the possibility of immunotherapy becoming a potent new class of cancer treatment in addition to traditional surgery, radiation, chemotherapy, and targeted therapy. Merck’s drug, like a number of others this year, has been given the FDA’s coveted “breakthrough” designated that’s designed to help get it through clinical trials and onto the market fast.
“We’re very, very excited about this program,” says Eric Rubin, Merck’s vice president for oncology clinical development.“My background is mostly in academia, and I’ve always been looking to be involved in something like this. I’m quite happy to put the resources of Merck behind developing this antibody.”
Bristol-Myers blazed a trail in this class of treatment two years ago when it won FDA approval of ipilimumab (Yervoy), a drug that releases a braking mechanism on the immune system called CTLA-4. That drug has shown it can extend lives of melanoma patients by a median of four months, although it can cause serious side effects, like inflammation of the intestines (colitis).
The data from the Merck study are still preliminary, and it will take more follow-up of patients before full conclusions can be drawn. But here’s the basic idea of what the company is trying to do.
Merck’s experimental antibody, also known as MK-3475, is designed to block a protein target called PD-1 which scientists believe is involved in allowing tumors to disguise themselves from the immune system. By inhibiting PD-1 or related targets, Merck and the other companies are hoping to unleash the power of immune system T cells to recognize and kill tumor cells, as if they were an invading virus or bacteria.
Merck has tested its experimental immunotherapy against a variety of tumor types, but its main presentation today will show what it did against melanoma. The study enrolled 135 patients with advanced melanoma, some of whom had gotten previous treatment with ipilimumab, and some who hadn’t. They were assigned to get a low dose of the injectable antibody every three weeks, a high dose every three weeks, or a high dose every two weeks.
The best results were on the high dose given every two weeks, researchers said. In that group of patients, 52 percent experienced some tumor shrinkage, and 10 percent had their tumors completely go away, researchers said. While there was no control group in this study—making it impossible to do a direct comparison of this drug to something else—historical studies have suggested that only about 5 percent of these patients can expect to see tumor shrinkage on standard chemotherapy, Rubin says. The response rates were similar for patients who previously got an immunotherapy, and those who hadn’t.
While tumor shrinkage rates can suggest a drug is working early on, they don’t mean much if the tumors find a way to bounce back quickly and spread again. But the Merck drug, like other immunotherapies, showed an intriguing ability to generate long-lasting tumor shrinkage rates. Researchers still don’t know how long the responses will last, but the patients have been followed for a median time of 11 months, and not enough have seen their disease worsen to provide a valid estimate of how long the drug works.
“These are clearly much more sustained responses than are seen with targeted agents or chemotherapy. That’s what makes this class such an impressive class,” Rubin says. “Presumably the reason it’s happening is you are re-training the immune system to fight cancer, and it becomes more difficult for the cancer to avoid that. Tumors are dynamic and can change, but the immune system is dynamic and can also change. It’s difficult for the cancer to escape that.”
Any time a drug works to stimulate the immune system, there’s a chance it can go too far, damaging healthy tissues, and causing autoimmunity. Most of the drug-related adverse events in this Merck study were mild to moderate, and included fatigue (30 percent of patients), rash (21 percent), pruritis /itching (21 percent), and diarrhea (20 percent). There were six mild to moderate cases of pneumonitis, a worrisome inflammatory condition of the lungs. The overall rate of side effects was lower than what researchers have seen with prior immunotherapy, like Bristol’s ipilimumab (Yervoy).
Based on the results, Merck is moving ahead with four new clinical trials that are enrolling 600 patients. One will test the Merck drug in patients with advanced melanoma, and another study will enroll patients with non-small cell lung cancer. The company is also running studies for a tough-to-treat form of breast cancer, bladder cancer that has spread, and head and neck cancer.
The company is holding a webcast briefing today at 2 pm Eastern/1 pm Central/11 am Pacific to discuss its cancer research programs at ASCO. Click here to follow the presentation.