-
Objective response rate was 32% in Opdivo treated patients and
11% in the reference arm of chemotherapy-treated patients
-
Majority (95%) of responses were ongoing in Opdivo treated
patients and median duration of response was not reached
-
Overall frequency of adverse events was lower with Opdivo
compared to chemotherapy; Opdivo treatment-related adverse events were
managed using recommended treatment algorithms
PRINCETON, N.J.--(BUSINESS WIRE)--
Bristol-Myers
Squibb Company (NYSE:BMY) today announced positive results from
CheckMate -037, a Phase 3 randomized, controlled open-label study of Opdivo
(nivolumab), an investigational PD-1 immune checkpoint inhibitor,
versus investigator’s choice chemotherapy (ICC) in patients with
advanced melanoma who were previously treated with Yervoy
(ipilimumab). Based on a planned interim analysis of the co-primary
endpoint, the objective response rate (ORR) was 32% (95% CI = 24, 41) in
the Opdivo arm (n=120) and 11% (95% CI = 4, 23) in the ICC
reference arm (n=47) in patients with at least six months of follow up.
The majority (95%) of responses were ongoing in the Opdivo arm
and the median duration of response was not reached. ORR was based on
RECIST criteria as evaluated by an independent radiologic review
committee (IRRC). These data were highlighted at a ESMO 2014 Congress
press briefing today in Madrid and will be presented during the
Presidential Symposium at 4 p.m. CEST (Abstract #LBA3_PR).
“These data are important as they mark the first presentation of results
from a Phase 3 randomized study for the PD-1 immune checkpoint inhibitor
class,” said Jeffrey S. Weber, MD, Ph.D., director of the Donald A. Adam
Comprehensive Melanoma Research Center at Moffitt Cancer Center.
“Additionally, the response rate and duration of response in patients
treated with Opdivo are consistent with findings from the early
Phase 1 trial in previously treated advanced melanoma (Study -003).”
Safety was reported on all patients treated in the Opdivo (n=268)
and ICC (n=102) arms. The majority of Opdivo treatment-related
adverse events (AEs) were Grade 1/2 and managed using recommended
treatment algorithms. Grade 3/4 drug-related AEs were less frequent for
the Opdivo arm (9% versus 31% of patients treated chemotherapy).
Serious Grade 3/4 drug-related AEs were reported in 5% and 9% of
patients treated with Opdivo and ICC, respectively. There was no
Grade 3/4 pneumonitis (inflammatory lung disease) with Opdivo.
Discontinuations due to drug-related AEs, of any grade, occurred in 2%
of Opdivo-treated patients and 8% of patients administered ICC.
There were no deaths related to study drug toxicity.
“This second set of positive Phase 3 data for Opdivo in patients
with advanced melanoma supports a deeper understanding of the potential
of immuno-oncology in this disease,” said Michael Giordano, M.D., senior
vice president, Head of Development, Oncology. “These results confirm
our belief in the potential of immuno-oncology, and our broad
development program continues to evaluate Opdivo in advanced
melanoma across lines of therapy, both as a single agent and as part of
a combination regimen.”
In June, Bristol-Myers Squibb announced that a randomized blinded
comparative Phase 3 study evaluating Opdivo versus dacarbazine in
patients with previously untreated BRAF wild-type advanced melanoma
(CheckMate -066) was stopped early because an analysis conducted by the
independent Data Monitoring Committee showed evidence of superior
overall survival in patients receiving Opdivo compared to the
control arm. The Company is working with investigators on the future
presentation and publication of the results from CheckMate -066.
Bristol-Myers Squibb has proposed the name Opdivo (pronounced
op-dee-voh), which, if approved by health authorities, will serve
as the trademark for nivolumab.
About CheckMate 037
CheckMate -037 is a Phase 3 randomized, open-label study (n=370)
designed to estimate the ORR in the Opdivo arm and compare the OS
of patients treated with Opdivo versus those patients
administered ICC. Patients in the trial were randomized 2:1 to receive Opdivo
3 mg/kg by intravenous infusion every two weeks (n=268) or ICC
(dacarbazine 1000 mg/m2 every three weeks or carboplatin
(AUC) 6 plus paclitaxel 175 mg/m2 every three weeks; n=102)
until progression or unacceptable toxicity. Patients were classified by
PD-1 ligand expression, BRAF status (wild type or mutated) and best
response to prior treatment with Yervoy. Co-primary endpoints of
the study are ORR and overall survival (OS). Response, as measured by
standard RECIST 1.1 criteria by an IRRC, was assessed nine weeks after
randomization, every six weeks for the first 12 months and then every 12
weeks. An interim analysis of OS had not taken place at the time of the
ORR analysis.
About Opdivo
Cancer cells may exploit “regulatory” pathways, such as checkpoint
pathways, to hide from the immune system and shield the tumor from
immune attack. Opdivo is an investigational, fully-human PD-1
immune checkpoint inhibitor that binds to the checkpoint receptor PD-1
(programmed death-1) expressed on activated T-cells.
Bristol-Myers Squibb has a broad, global development program to study Opdivo
in multiple tumor types consisting of more than 35 trials – as
monotherapy or in combination with other therapies – in which more than
7,000 patients have been enrolled worldwide. Among these are several
potentially registrational trials in non-small cell lung cancer (NSCLC),
melanoma, renal cell carcinoma (RCC), head and neck cancer, glioblastoma
and non-Hodgkin lymphoma.
In 2013, the FDA granted Fast Track designation for Opdivo (nivolumab)
in NSCLC, melanoma and RCC. In April 2014, the company initiated a
rolling submission with the FDA for Opdivo in third-line
pre-treated squamous cell NSCLC and expects to complete the submission
by year-end. The FDA granted Opdivo Breakthrough Therapy
Designation in May 2014 for the treatment of patients with Hodgkin
lymphoma after failure of autologous stem cell transplant and
brentuximab. On July 4, Ono Pharmaceutical Co. announced that Opdivo
received manufacturing and marketing approval in Japan for the
treatment of patients with unresectable melanoma, making Opdivo
the first PD-1 immune checkpoint inhibitor to receive regulatory
approval anywhere in the world. On September 26, Bristol-Myers Squibb
announced that the FDA accepted for priority review the BLA for
previously treated advanced melanoma, and the Prescription Drug User Fee
Act (PDUFA) goal date for a decision is March 30, 2015. The FDA also
granted Opdivo Breakthrough Therapy status for this indication.
In the European Union, the European Medicines Agency (EMA) has validated
for review the Marketing Authorization Application (MAA) for Opdivo
in advanced melanoma. The application has also been granted accelerated
assessment by the EMA’s Committee for Medicinal Products for Human Use
(CHMP).
About Advanced Melanoma
Melanoma is a form of skin cancer characterized by the uncontrolled
growth of pigment-producing cells (melanocytes) located in the skin.
Metastatic melanoma is the deadliest form of the disease, and occurs
when cancer spreads beyond the surface of the skin to the other organs,
such as the lymph nodes, lungs, brain or other areas of the body. The
incidence of melanoma has been increasing for at least 30 years. In
2012, an estimated 232,130 melanoma cases were diagnosed globally.
Melanoma is mostly curable when treated in its early stages. However, in
its late stages, the average survival rate has historically been just
six months with a one-year mortality rate of 75 percent, making it one
of the most aggressive forms of cancer.
Immuno-Oncology at Bristol-Myers Squibb
Surgery, radiation, cytotoxic or targeted therapies have represented the
mainstay of cancer treatment over the last several decades, but
long-term survival and a positive quality of life have remained elusive
for many patients with advanced disease.
To address this unmet medical need, Bristol-Myers Squibb is leading
advances in the innovative field of immuno-oncology, which involves
agents whose primary mechanism is to work directly with the body’s
immune system to fight cancer. The company is exploring a variety of
compounds and immunotherapeutic approaches for patients with different
types of cancer, including researching the potential of combining
immuno-oncology agents that target different and complementary pathways
in the treatment of cancer.
Bristol-Myers Squibb is committed to advancing the science of
immuno-oncology, with the goal of changing survival expectations and the
way patients live with cancer.
About the Bristol-Myers Squibb and Ono
Pharmaceutical Collaboration
In 2011, through a collaboration agreement with Ono Pharmaceutical,
Bristol-Myers Squibb expanded its territorial rights to develop and
commercialize Opdivo globally except in
Japan, South Korea and Taiwan, where Ono had retained all rights to the
compound at the time. On July 23, 2014, Bristol-Myers Squibb and Ono
Pharmaceutical further expanded the companies’ strategic collaboration
agreement to jointly develop and commercialize multiple immunotherapies
– as single agents and combination regiments – for patients with cancer
in Japan, South Korea and Taiwan.
About Bristol-Myers Squibb
Bristol-Myers Squibb is a global pharmaceutical company whose mission is
to discover, develop and deliver innovative medicines that help patients
prevail over serious diseases. For more information about Bristol-Myers
Squibb, visit www.bms.com,
or follow us on Twitter at http://twitter.com/bmsnews.
Bristol-Myers Squibb Forward-Looking Statement
This press release contains "forward-looking statements" as that term
is defined in the Private Securities Litigation Reform Act of 1995
regarding the research, development and commercialization of
pharmaceutical products. Such forward-looking statements are based on
current expectations and involve inherent risks and uncertainties,
including factors that could delay, divert or change any of them, and
could cause actual outcomes and results to differ materially from
current expectations. No forward-looking statement can be guaranteed.
Among other risks, there can be no guarantee that Opdivo will receive
regulatory approval in the U.S. or, if approved, that it will become a
commercially successful product. Forward-looking statements in this
press release should be evaluated together with the many uncertainties
that affect Bristol-Myers Squibb's business, particularly those
identified in the cautionary factors discussion in Bristol-Myers
Squibb's Annual Report on Form 10-K for the year ended December 31, 2013
in our Quarterly Reports on Form 10-Q and our Current Reports on Form
8-K. Bristol-Myers Squibb undertakes no obligation to publicly update
any forward-looking statement, whether as a result of new information,
future events or otherwise.
Source: Bristol-Myers Squibb Company