Squibb Company (NYSE: BMY) today announced interim results from the
expanded Phase 1 dose-ranging study 003 (n=296) of its investigational
anti-PD-1 immunotherapy (BMS-936558), which showed clinical activity in
patients with previously-treated non small-cell lung cancer (NSCLC),
metastatic melanoma and renal cell carcinoma (RCC). Anti-PD-1 is a
fully-human antibody that targets the inhibitory receptor expressed on
activated T-cells called PD-1 or programmed death-1. Objective response
rates (ORs) across dose cohorts, as measured by standard RECIST
criteria, ranged from 6% to 32% in NSCLC, 19% to 41% in metastatic
melanoma and 24% to 31% in RCC. Most responses were durable.
Drug-related serious adverse events occurred in 11% of patients who
received BMS-936558. Drug-related adverse events of special interest,
defined as those with potential immune-related etiology, were sometimes
severe and life-threatening.
The data on anti-PD-1 were published today in the New England Journal
of Medicine1 and featured in four oral
presentations at the 48th Annual Meeting of the American
Society of Clinical Oncology (Abstract # 2509, 4505, 7509 and 8507).
Additionally, abstracts from the NSCLC cohort (Abstract# 7509) and the
melanoma cohort (Abstract #8507) of study 003 have been chosen for the
Best of ASCO® educational program.
“Results from this Phase 1 study of anti-PD-1 showed clinical activity
across NSCLC, metastatic melanoma and RCC, adding to our scientific
understanding of the potential of immuno-oncology as a therapeutic
approach in the treatment of cancer,” said Dr. Thomas J. Lynch, Jr.,
director of Yale Cancer Center and physician-in-chief of the Smilow
Cancer Hospital at Yale-New Haven, which was involved in the clinical
trials. “These data are encouraging and support further investigation of
anti-PD-1 in large-scale, randomized Phase 3 trials.”
“Immuno-oncology is a prioritized area of research and development at
Bristol-Myers Squibb and we plan to initiate registrational studies for
anti-PD-1 in NSCLC and RCC this year and late 2012, early 2013 for
metastatic melanoma,” said Brian
Daniels, senior vice president, Global Development and Medical
Affairs, Bristol-Myers Squibb. “Our commitment to advancing the science
of immuno-oncology is underscored by the data presented at ASCO and
published in the New England Journal of Medicine, our ongoing
development programs for immuno-oncology assets including YERVOY®
(ipilimumab) and anti-PD-1, and the investment in the
International Immuno-Oncology Network, a collaboration with leading
cancer research centers.”
Data on a second investigational immunotherapy from Bristol-Myers
Squibb, anti-PD-L1 (BMS-936559), were also published today in the New
England Journal of Medicine2 and featured
in an oral presentation at ASCO (Abstract # 2510). BMS-936559 is
fully-human antibody that targets one of the immunosuppressive ligands
for PD-1, PD-L1, which is often expressed on tumor, stromal and immune
Through a collaboration agreement with Ono Pharmaceutical, Bristol-Myers
Squibb expanded its territorial rights to develop and commercialize
anti-PD-1 (BMS-936558/ONO-4538) globally except in Japan, Korea and
Taiwan where Ono has retained all rights to the compound.
Study 003 Interim Results
Objective responses, as measured by standard RECIST criteria, were
observed in patients treated with BMS-936558 across dose cohorts and
across the NSCLC (6% to 32%), metastatic melanoma (19% to 41%) and RCC
(6% to 32%) tumor types. Most responses were durable with response
durations ≥1 year in 65% of responders with ≥1 year follow-up.
The spectrum, frequency, and severity of treatment-related adverse
events (AEs) were generally similar across tested dose levels. Common
drug-related AEs included fatigue, rash, diarrhea, decreased appetite
and nausea, with Grade 3-4 AEs observed in 14% of patients. Drug-related
AEs of special interest, defined as those with potential immune-related
etiologies, included pneumonitis, vitiligo, colitis, hepatitis,
hypophysitis and thyroiditis. Hepatic or gastrointestinal AEs
were managed with treatment interruption and administration of
corticosteroids, as needed. Endocrine disorders were managed with
replacement therapy. Drug-related pneumonitis occurred in 9 of 296 (3%)
patients. Grade 3-4 pneumonitis developed in 3 (1%) patients and was
associated with 3 drug-related deaths.
About Study 003
Study 003 is a dose-ranging Phase 1 study (n=296) evaluating the safety,
antitumor activity and pharmacokinetics of BMS-936558 in patients with
advanced melanoma (n=104), non-small cell lung cancer (n=122), renal
cell carcinoma (n=34), castration-resistant prostate cancer (n=17) and
colorectal cancer (n=19).
Eligible patients were administered BMS-936558 as an intravenous
infusion every 2 weeks of each 8-week treatment cycle. Cohorts of three
to six patients per dose level (0.1, 0.3, 1.0, 3.0 or 10 mg/kg) were
enrolled sequentially. Patients continued treatment ≤2 years (12
cycles), unless they experienced complete response, unacceptable
toxicity, progressive disease or withdrew consent. In clinically stable
patients, treatment could be continued beyond apparent initial disease
progression until confirmed progression, as defined by proposed immune
response criteria. Patients with stable disease (SD) or an ongoing OR at
the completion of treatment were followed for ≤1 year and offered
retreatment for one additional year if their disease progressed. OR was
defined as complete (CR) or partial response (PR).
Immuno-Oncology at Bristol-Myers Squibb
Immuno-oncology, which focuses on the scientific potential of harnessing
the unique properties of the immune system to fight cancer, is a
prioritized area of research and development at Bristol-Myers Squibb.
The Company is committed to leading advances in this important field of
research and is exploring a variety of innovative compounds and
immunotherapeutic approaches to help address significant unmet medical
needs in a broad range of cancers. More information can be found at www.BMSImmunoOncology.com.
About Bristol-Myers Squibb
Bristol-Myers Squibb is a global biopharmaceutical 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.
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 the all of the
compounds described in this release will move from exploratory
development into full product development, that the clinical trials of
these compounds will support regulatory filings, or that all of the
compounds will receive regulatory approvals or, if approved, that they
will all become commercially successful products. 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, 2011, 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.
1 Topalian et al the Johns Hopkins University School of
Medicine and the Sidney Kimmel Comprehensive Cancer Center.
2 Brahmer et al the Johns Hopkins University School of
Medicine and the Sidney Kimmel Comprehensive Cancer Center.