Bristol melanoma drug combo marks new advance in immunotherapy..melanoma..Jim Breitfeller

Reuters
6:01 pm, May 15, 2013

(For more stories on new cancer data, see )

By Julie Steenhuysen

CHICAGO, May 15 (Reuters) - Melanoma patients treated with
two Bristol-Myers Squibb drugs fared much better than
those who received either of the medications individually, a new
advance for treatments that harness the body's immune system to
fight cancer.

Bristol released preliminary data from the early-stage trial
on Wednesday, with more detailed results expected to highlight
the American Society of Clinical Oncology's annual meeting in
Chicago that starts at the end of the month.

Patients in the study received Bristol's immunotherapy
Yervoy, which is already on the market, and an experimental
treatment called Nivolumab that attacks an
immune-system-inhibiting protein called PD-1. The combined
treatment shrank tumors in a majority of patients.

"We have never seen this with immunotherapy before," said Dr
Jedd Wolchok of New York's Memorial Sloan-Kettering Cancer
Center. "The vast majority of patients have a decrease in tumor
burden. In melanoma, we're used to seeing the opposite," he said
of the notoriously difficult-to-treat form of skin cancer.

Investors have been eager to see results of the study, with
Bristol shares reaching a 10-year high on Wednesday in advance
of the data release.

Both drugs are designed to target different parts of the
immune system that act as brakes even when cancer is present,
preventing immune cells from attacking tumors. By gumming up
these brakes, the drugs free the immune system to attack and
kill tumor cells.

Approved in 2011, Yervoy, or ipilimumab, was the first drug
to significantly extend survival in patients with advanced
melanoma, the most deadly form of skin cancer. It boosts the
immune system by blocking the action of a protein called CTLA-4.

Nivolumab, which is in late-stage testing, targets a protein
called PD-1, or Programmed Death receptor, a new class of
immune-system drugs that shows promise not only in melanoma but
also in lung and kidney cancer.

Typically, only about 11 percent of patients respond to
Yervoy, and recent studies in melanoma suggest Nivolumab
produces a response rate of about 41 percent, Wolchok told a
news briefing.

The current study looked at the combination of the two drugs
based on animal studies suggesting that together they might
work better than either drug alone.

Wolchok reported results for 86 patients in the trial as of
February 2013, including 52 patients who were on both drugs at
the same time. In one of the treatment groups, which will likely
advance to late-stage trials, 53 percent of patients treated
with both Yervoy and Nivolumab simultaneously had an objective
response - defined as at least a 50 percent reduction in tumor
size.


RAPID RESPONSE

Dr Sandra Swain, president of ASCO, called the findings
remarkable. "This combination treatment led to a very rapid and
profound lasting tumor shrinkage. Ninety percent of patients are
still responding," she said.

Three out of four patients who responded to the dual
treatment had tumor shrinkage in the first three months.

Among the most advanced melanoma patients, Wolchok said the
combination of the two drugs produced "rapid and deep
regressions, with many showing more than 80 percent tumor
regression by the time of the first scan."

Overall, most patients had some decrease in tumor size. In
31 percent of all patients taking the dual therapy, tumors
shrank by greater than 80 percent, Wolchok said.

In 18 percent of patients, the drug combination produced a
complete response, meaning tumors were no longer detectable,
Wolchok said in an interview. He said they do not yet have any
data on relapse because 90 percent of patients who responded to
the treatment are continuing to benefit.

The combination also appeared to be safe. About half of
patients who got both treatments had a drug-related side effect,
but in most cases it was linked to elevations in enzymes related
to the pancreas and liver.

"These are reversible, sometimes without treatment," Wolchok
said, although some patients did need a short course of the
steroid prednisone. There were no drug-related deaths.

"We really didn't see anything new with the combination"
related to safety, he said.

Bristol-Myers plans a late-stage clinical trial that looks
at both drugs in combination, as well as each separately, in
patients with melanoma. It has also begun testing the same
combination in lung cancer and renal-cell cancer.

"We view the combination of immunotherapy as a significant
one that we'll be pursuing," Michael Giordano, Bristol-Myers'
senior vice president of global development for oncology and 
immunology, said in an interview.

So far, Bristol-Myers is furthest ahead in its development
of a PD-1 inhibitor, but Merck & Co Inc last month won
designation from the U.S. Food and Drug Administration as a
"breakthrough therapy," which could speed development and
regulatory review of the product.

In a recent note, Bernstein Research analyst Tim Anderson
said Bristol's anti-cancer drug PD-1 "is the major driver of
investor interest at the moment," but said awareness is building
that competitors "may not be very far behind."

Last November, Merck reported results from a trial of its
drug in patients with advanced melanoma and saw a 47 percent
response rate. In that trial, the drug benefited patients who
had previously been treated with ipilimumab but had not
responded, said Dr. Gary Gilliland, a Merck senior vice
president for oncology.

Merck plans to present an update of this study on June 2 at
the ASCO meeting. Gilliland said the company also is studying
its treatment in so-called triple-negative breast cancer, a
hard-to-treat form of the disease, as well as head and neck
cancer and bladder cancer.

Other companies pursuing the PD-1 or related pathways
include Roche, GlaxoSmithKline and Teva
.

"PD-1 is arguably the most exciting breakthrough in cancer
therapy in a decade," said ISI Group analyst Mark Schoenebaum.
"There is speculation that it might offer a cure for some
patients with solid tumors. This is unprecedented."

(Additional reporting by Bill Berkrot in New York; Editing by
Michele Gershberg and Prudence Crowther)

“It is not the strongest of the species that survives, nor the most intelligent, but the one most responsive to change.” ~
Charles Darwin~
 Take Care,
 Jimmy B