Data from KEYNOTE-006 Study Presented at AACR Annual Meeting
and Published in the New England Journal of Medicine
KIRKLAND, QC, April 19, 2015 /CNW Telbec/ - Merck (NYSE: MRK),
known as MSD outside the United
States and Canada, today
announced results from the randomized, pivotal Phase 3 study,
KEYNOTE-006, in the treatment of unresectable advanced melanoma. In
the study, pembrolizumab was statistically superior to ipilimumab
for progression-free survival (PFS), overall survival (OS), and
overall response rate (ORR). On March 24,
2015, Merck announced that KEYNOTE-006 would be stopped
early based on these data. The results will be presented today at
the American Association for Cancer Research (AACR) Annual Meeting
by Dr. Antoni Ribas of Jonsson
Comprehensive Cancer Center, University of
California, Los Angeles (abstract # CT101, included in the
AACR press program), and were also published today in the New
England Journal of Medicine.
"Improving survival is the ultimate objective in treating
patients with cancer. In this important study in advanced melanoma,
pembrolizumab was statistically superior to ipilimumab for
progression-free survival and overall survival, and also
demonstrated a lower frequency of severe adverse events." said Dr.
Caroline Robert, head of Dermatology
at Gustave Roussy, Villejuif and Paris-Sud University Cancer
Campus, Grand Paris and lead author of the New England Journal
of Medicine publication.
"Our goal with the pembrolizumab development program is to help
improve long-term disease control and survival for people with a
wide range of cancers," said Dr. Roger
Perlmutter, president, Merck Research Laboratories. "The
KEYNOTE-006 study compared two immunotherapies that target distinct
immune checkpoint pathways, PD-1 and CTLA-4. In this study, our
investigational anti-PD-1 antibody, pembrolizumab, improved overall
survival by more than 30 percent compared to ipilimumab, an
anti-CTLA-4 antibody, in the treatment of advanced melanoma. We
look forward to filing these data with health authorities around
the world."
"Metastatic melanoma is a devastating disease with a very poor
prognosis and historically, therapeutic options have been limited,"
explained Dr. Teresa Petrella, Head
of the Melanoma Disease Site Group at the Odette Cancer Centre,
Sunnybrook Health Sciences Centre. "However, new agents and
treatment strategies are changing the landscape of the management
of melanoma. The rapidly evolving field of immuno-oncology is
finally bringing new hope to cancer patients in Canada." She adds, "Many Canadian
melanoma patients participated in the KEYNOTE-006 trial. This is an
exciting time in melanoma, and new therapies that have now shown an
improvement in overall survival represent a potential new treatment
option in a population with a high unmet need."
KEYNOTE-006 Results in the Front-Line Treatment of Advanced
Melanoma
KEYNOTE-006 is a global, open-label, randomized, pivotal, Phase
3 study (ClinicalTrials.gov, NCT01866319) of 834 patients from 16
countries with unresectable stage III or IV advanced melanoma with
no more than one prior systemic therapy. Patients received
pembrolizumab 10 mg/kg every two weeks (n=279), pembrolizumab 10
mg/kg every three weeks (n=277), or four cycles of ipilimumab 3
mg/kg every three weeks (n=278). The primary endpoints were PFS and
OS; secondary endpoints were ORR, duration of response, and safety.
Tumour response was assessed at week 12, then every six weeks
thereafter by independent central review per RECIST 1.1. This first
presentation of data from KEYNOTE-006 is based on interim analyses
conducted for PFS with a data cut-off of September 3, 2014 (median follow-up, 7.9 months)
and for OS with a data cut off of March 3,
2015 (median follow-up, 13.8 months).
Data Showed Pembrolizumab was Statistically Superior to
Ipilimumab for PFS, OS and ORR
The median PFS for pembrolizumab was 5.5 months (2-week group)
and 4.1 months (3-week group) compared to 2.8 months for ipilimumab
(HR 0.58, P<0.00001 for the pembrolizumab groups vs.
ipilimumab, 95% CI, 0.46-0.72 for 2-week group and 0.47-0.72 for
3-week group, respectively). The estimated 6-month PFS rates for
the pembrolizumab and ipilimumab arms were 47.3 percent, 46.4
percent and 26.5 percent, respectively. One-year OS for
pembrolizumab was 74.1 percent (2-week group) and 68.4 percent
(3-week group) compared to 58.2 percent for ipilimumab (HR 0.63
[95% CI, 0.47-0.83, P=0.00052] for the 2-week group and HR
0.69 [95% CI, 0.52-0.90, P=0.00358] for the 3-week group).
At the time of analysis, median overall survival was not reached in
any treatment group.
ORR for pembrolizumab was 33.7 percent (2-week group) and 32.9
percent (3-week group) compared to 11.9 percent for ipilimumab
(P=0.00013 for 2-week group; P=0.00002 for 3-week
group); complete response rates were 5.0 percent, 6.1 percent, and
1.4 percent, respectively. Responses were ongoing in 89.4 percent
(2-week group) and 96.7 percent (3-week group) of
pembrolizumab-treated patients and in 87.9 percent of
ipilimumab-treated patients. Median duration of response was not
reached for pembrolizumab 3-week group (42+ to 246+) and ipilimumab
(33+ to 239+).
The efficacy and safety profiles were similar between the two
pembrolizumab schedules evaluated in the study. Two previous
studies, KEYNOTE-001 and KEYNOTE-002, demonstrated that the
efficacy and safety were similar among the pembrolizumab doses and
schedules evaluated; 10 mg/kg every two weeks, 10 mg/kg every three
weeks, and 2 mg/kg every three weeks.
Safety Findings from KEYNOTE-006
The safety profile of pembrolizumab in this study was generally
consistent with previously reported safety data. The most common
treatment-related adverse events of any grade occurring in the
pembrolizumab groups were fatigue, diarrhea, rash, and pruritus.
For ipilimumab, the most frequent treatment-related adverse events
were pruritus, diarrhea, fatigue, and rash. Grade 3 to 4
treatment-related adverse events occurred in 13.3 percent (2-week
group) and 10.1 percent (3-week group) of patients treated with
pembrolizumab and in 19.9 percent for ipilimumab. Discontinuation
due to treatment-related adverse events was less frequent with
pembrolizumab (2-week group and 3-week group) than with ipilimumab
(4.0%, 6.9%, and 9.4%, respectively). One death in the ipilimumab
group was attributed to study treatment.
Treatment-related adverse events of an autoimmune or
immune-related nature most frequently observed with pembrolizumab
(2-week group and 3-week group) were hypothyroidism (10.1% and
8.7%) and hyperthyroidism (6.5% and 3.2%). With ipilimumab, colitis
occurred in 8.2 percent of patients. Grade 3 to 4 inflammatory or
immune-mediated treatment events reported in more than 1 percent of
pembrolizumab-treated patients (2-week group and 3-week group) were
colitis (1.4% and 2.5%) and hepatitis (1.1% and 1.8%), and in
ipilimumab-treated patients were colitis (7.0%) and hypophysitis
(1.6%).
About Pembrolizumab
Pembrolizumab is a humanized monoclonal antibody that blocks the
interaction between PD-1 and its ligands, PD-L1 and PD-L2. By
binding to the PD-1 receptor and blocking the interaction with the
receptor ligands, pembrolizumab releases the PD-1 pathway-mediated
inhibition of the immune response, including the anti-tumour immune
response.
Merck is advancing a broad and fast-growing clinical development
program for pembrolizumab with more than 85 clinical trials –
across more than 30 tumour types and over 14,000 patients – both as
a monotherapy and in combination with other therapies.
About Melanoma
Melanoma, the most serious form of skin cancer1, is
characterized by the uncontrolled growth of pigment-producing
cells. The incidence of melanoma has been increasing over the past
four decades – approximately 232,130 new cases were diagnosed
worldwide in 2012.
In Canada, in 2014, it was
estimated that 6,500 Canadians would be diagnosed with melanoma,
while 1,050 Canadians would die from melanoma2.
The five-year survival rates for advanced or metastatic melanoma
(Stage IV) are estimated to be 15 to 20 percent.
Our Focus on Cancer
Our goal is to translate breakthrough science into biomedical
innovations to help people with cancer worldwide. For Merck
Oncology, helping people fight cancer is our passion, supporting
accessibility to our cancer medicines is our commitment, and
pursuing research in immuno-oncology is our focus to potentially
bring new hope to people with cancer. For more information about
our oncology clinical trials, visit
www.merck.com/clinicaltrials.
About Merck
Today's Merck is a global healthcare leader working to help the
world be well. Merck is known as MSD outside Canada and the
United States. Through our prescription medicines, vaccines,
biologic therapies, and consumer care and animal health products,
we work with customers and operate in more than 140 countries to
deliver innovative health solutions. We also demonstrate our
commitment to increasing access to healthcare through far-reaching
policies, programs and partnerships. For more information about our
operations in Canada, visit
www.merck.ca.
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# # #
1 Medline Plus. (May
2012). Melanoma. Retrieved on April
18, 2015 from
http://www.nlm.nih.gov/medlineplus/ency/article/000850.htm
2 Canadian Cancer Society. Melanoma.
Retrieved on April 18, 2015 from
http://www.cancer.ca/en/cancer-information/cancer-type/skin-melanoma/statistics/?region=sk
SOURCE Merck