* Among those who got the highest dose, 52 percent responded
* Company to start phase-three trial in third quarter
By Julie Steenhuysen
CHICAGO, June 2 A Merck & Co drug
designed to unmask tumor cells and mobilize the immune system
into fighting cancer helped shrink tumors in 38 percent of
patients with advanced melanoma in an early-stage study, U.S.
researchers said on Sunday.
Based on the findings about the drug lambrolizumab,
published in the New England Journal of Medicine and presented
at the American Society of Clinical Oncology meeting in Chicago,
Merck says it will move directly into a late-stage clinical
trial, which will start in the third quarter.
"This is a top priority at Merck," Dr. Gary Gilliand, senior
vice present and head of oncology at Merck Research Laboratories
said in a meeting with investors. "We're going flat out to
deliver benefit to patients with this novel mechanism."
The moves may heap pressure on market leader Bristol-Myers
Squibb, maker of Yervoy - the only approved immune
system drug for the treatment of advanced melanoma, the
deadliest form of skin cancer.
Bristol-Myers is conducting three phase-three studies of its
own drug called nivolumab in advanced melanoma, and is studying
the drug's effect on a range of other cancers, including lung
Both nivolumab and lambrolizumab are part of a promising new
class of drugs that disable programmed death 1 or PD-1, a
protein that keeps the immune system from spotting and attacking
"Even though it's (lambrolizumab) the second player in the
field and even though it's all early, it impressed me," said Dr.
Antoni Ribas of the University of California Los Angeles'
Jonsson Comprehensive Cancer Center, the lead author of the
Last month, the U.S. Food and Drug Administration deemed the
treatment a "breakthrough therapy," a designation FDA cancer
drugs chief Dr. Richard Pazdur described as
Results of an early-stage study of nivolumab in advanced
melanoma released at the cancer meeting showed 31 percent of
patients overall responded to different doses of the drug. Among
those who took the 3 milligram per kilogram dose, 41 percent of
patients responded. The drug response lasted an average of two
years, and in many patients the drug kept working even after
they stopped taking it.
Analysts expect the drugs to generate billions of dollars in
sales. Nivolumab alone is forecast to have sales of $1.2 billion
in 2017, according to Wall Street analysts tracked by Thomson
Merck's results are from the first clinical trial of
lambrolizumab in advanced melanoma. They are based on analysis
of 135 patients with metastatic melanoma who were divided into
three groups with different treatment regimens.
Overall, lambrolizumab resulted in 38 percent of patients
having confirmed improvement of their cancer across all dose
levels given after 12 weeks of treatment. But there was a wide
range among doses, with only a 25 percent rate among patients
who got the lowest dose and 52 percent among those who got the
highest dose. In the highest dose group, 10 percent had a
complete response, meaning their tumors could not be detected on
Side effects were generally mild and included fatigue,
fevers, skin rash, loss of skin color and muscle weakness. More
severe side effects were seen in 13 percent of patients,
including inflammation of the lung or kidney and thyroid
"This study is showing the highest rate of durable melanoma
responses of any drug we have tested thus far in this cancer,
and it is doing it without serious side effects in the great
majority of patients," Ribas said.
Merck said it plans to start a late-stage randomized trial
of the drug in melanoma and in non-small cell lung cancer in the
third quarter of this year.
The company recently started a global, randomized mid-stage
study of the drug versus standard chemotherapy in patients whose
disease had progressed. And it is studying the drug as a
treatment for triple negative breast, metastatic bladder and
head and neck cancers.
Researchers at the meeting marveled at responses to new
immune system treatments after decades of failed studies among
patients with melanoma.
Only about one in five patients respond to Yervoy, approved
in 2011 as the first immunotherapy to extend survival in
patients with advanced melanoma. Yervoy works by blocking
CTLA-4, a different molecule that also keeps the immune system
from attacking cancer.
Ribas said he has followed one patient on Yervoy for 12
years now. "She's not supposed to be around, and she's alive and
well and melanoma free. That is why we've been doing these
immunotherapies," he said.
With Yervoy, Ribas said these types of responses were few
and far between. With the new PD-1 drugs, they are much more
common, with fewer side effects.
However, an early-stage Bristol-Myers' study released this
month showed that 53 percent of patients who got a combination
of Yervoy and nivolumab had at least a 50 percent reduction in
tumor size, with fewer side effects.
Tim Turnham, executive director of the Melanoma Research
Foundation, said combination treatments would make a major
difference for patients because they help overcome cancer's
"sneaky" ability to evade treatment. But, at this point, he
said, "Nobody knows which one is better."