Approval based on results from the Phase 1/2
KRYSTAL-1 study where KRAZATI in combination with cetuximab showed
an objective response rate of 34% in pretreated patients with
locally advanced or metastatic CRC harboring a KRASG12C
mutation1
Second FDA approval for KRAZATI - reinforcing
its potential across tumor types
Bristol Myers Squibb (NYSE: BMY) today announced that the
U.S. Food and Drug Administration (FDA) has granted accelerated
approval for KRAZATI® (adagrasib) in combination with cetuximab as
a targeted treatment option for adult patients with
KRASG12C-mutated locally advanced or metastatic colorectal cancer
(CRC), as determined by an FDA-approved test, who have received
prior treatment with fluoropyrimidine-, oxaliplatin-, and
irinotecan-based chemotherapy. This indication is approved under
accelerated approval based on objective response rate (ORR) and
duration of response (DOR) results. Continued approval for this
indication may be contingent upon verification and description of a
clinical benefit in a confirmatory trial.
“CRC with a KRASG12C mutation occurs in approximately 3-4% of
CRC patients and has historically been challenging to treat,”2 said
Rona Yaeger, MD, Gastrointestinal Oncologist & Early Drug
Development Specialist, Memorial Sloan Kettering Cancer Center.
“The FDA approval of KRAZATI combined with cetuximab now provides a
new treatment option to these patients when their tumors do not
respond well to prior therapies.”
The approval is based on results from cohorts of the Phase 1/2
KRYSTAL-1 open-label study which evaluated KRAZATI (600 mg tablets
administered orally twice daily) in combination with cetuximab in
94 patients with heavily pretreated CRC harboring a KRASG12C
mutation. The study met its primary endpoint, with a confirmed ORR
of 34% (n=94, 95% CI: 25-45) for KRAZATI with cetuximab, all of
which were partial responses. The median DOR, one of the secondary
endpoints, was 5.8 months (95% CI: 4.2-7.6).1 Current late-line
standard of care options result in limited response rates (ORR
1-6%) after progression on chemotherapy ± VEGF/VEGFR
inhibitors.3,4
KRAZATI is associated with the following Warnings &
Precautions: Gastrointestinal adverse reactions including diarrhea,
nausea, and vomiting, QTc interval prolongation, hepatotoxicity,
and interstitial lung disease (ILD)/pneumonitis.1 Please see
Important Safety Information below.
“Today’s approval of KRAZATI in CRC is the second in the U.S.
for this therapy and the first for BMS' recently expanded oncology
portfolio. This is an important milestone for BMS and the patients
we serve as we deliver on our commitment to provide innovative
medicines for cancer,” said Wendy Short Bartie, senior vice
president, U.S. Oncology and Hematology at Bristol Myers Squibb.
“We are proud to make KRAZATI - the first KRASG12C inhibitor to be
FDA approved beyond non-small cell lung cancer - available to CRC
patients, and look forward to further evaluating KRAZATI through
our ongoing development program.”
In 2022, the FDA granted breakthrough therapy designation for
KRAZATI in combination with cetuximab for patients with
KRASG12C-mutated advanced CRC whose cancer has progressed following
prior treatment with certain chemotherapy and an anti-VEGF
therapy.
KRAZATI is an irreversible inhibitor of KRASG12C with a long
half-life (23 hours), dose-dependent pharmacokinetics (PK), and
central nervous system (CNS) penetration, which, in combination
with cetuximab may enhance inhibition of KRAS-dependent signaling
or overcome adaptive feedback.
The company partnered with QIAGEN to develop a tissue-based
companion diagnostic (CDx) for KRAZATI that is now available.
KRAZATI is a registered trademark of Mirati Therapeutics, Inc.,
a Bristol Myers Squibb company.
About KRYSTAL-1
KRYSTAL-1 is an open-label, multicenter, multiple expansion
cohort Phase 1/2 trial to determine the safety and efficacy of
KRAZATI in patients with advanced colorectal cancer (CRC) that
harbor a KRASG12C mutation. The primary endpoint for the Phase 2
cohort of the KRYSTAL-1 study was objective response rate (ORR).
Secondary endpoints included duration of response (DOR).
The KRYSTAL-1 study was funded by Mirati Therapeutics, Inc., a
Bristol Myers Squibb company.
Select Safety Profile from
KRYSTAL-1
The safety profile for KRAZATI plus cetuximab was evaluated in
patients with KRASG12C-mutated, locally advanced or metastatic CRC,
and is consistent with previous reports and known safety profile of
each drug individually. Serious adverse reactions occurred in 30%
of 94 patients who received KRAZATI in combination with cetuximab.
The most common adverse reactions (≥20%) were rash, nausea,
diarrhea, vomiting, fatigue, musculoskeletal pain, hepatotoxicity,
headache, dry skin, abdominal pain, decreased appetite, edema,
anemia, dizziness, cough, constipation, and peripheral
neuropathy.1
About Colorectal Cancer
Colorectal cancer (CRC) is cancer that develops in the colon or
the rectum, which are part of the body’s digestive, or
gastrointestinal, system.5 CRC is the third most commonly diagnosed
cancer in the world.6 In 2024, it is estimated that there will be
approximately 106,590 new cases of the disease in the U.S.; it is
the second leading cause of cancer-related deaths in the U.S. among
men and women combined.7
KRAS is the most frequently mutated oncogene in human cancer and
is one that drives oncogenesis in up to 50% of patients with CRC.2
The KRASG12C mutation occurs in approximately 3-4% of CRC
cases.2
About KRAZATI®
(adagrasib)
KRAZATI (adagrasib) is a highly selective and potent oral
small-molecule inhibitor of KRASG12C that is optimized to sustain
target inhibition, an attribute that could be important to treat
KRASG12C-mutated cancers, as the KRASG12C protein regenerates every
24-48 hours.8 KRASG12C mutations act as oncogenic drivers and occur
in approximately 14% of non-small cell lung cancer (NSCLC;
adenocarcinoma) and 3% of several other cancers.9,10
In 2022, KRAZATI was granted accelerated approval for treatment
of adult patients with KRASG12C-mutated locally advanced or
metastatic NSCLC, as determined by an FDA-approved test, who have
received at least one prior systemic therapy. This indication is
approved under accelerated approval based on objective response
rate (ORR) and duration of response (DOR). Continued approval for
this indication may be contingent upon verification and description
of a clinical benefit in a confirmatory trial.
KRAZATI continues to be evaluated as a monotherapy and in
combination with other anti-cancer therapies in patients with
advanced KRASG12C-mutated solid tumors, including NSCLC and
CRC.
Please see U.S. Full Prescribing Information for KRAZATI.
INDICATIONS
KRAZATI in combination with cetuximab is indicated for the
treatment of adult patients with KRASG12C-mutated locally advanced
or metastatic colorectal cancer (CRC), as determined by an
FDA-approved test, who have received prior treatment with
fluoropyrimidine-, oxaliplatin-, and irinotecan-based
chemotherapy.
KRAZATI, as a single agent, is indicated for the treatment of
adult patients with KRASG12C-mutated locally advanced or metastatic
non-small cell lung cancer (NSCLC), as determined by an
FDA-approved test, who have received at least one prior systemic
therapy.
These indications are approved under accelerated approval based
on objective response rate (ORR) and duration of response (DOR).
Continued approval for these indications may be contingent upon
verification and description of a clinical benefit in confirmatory
trials.
IMPORTANT SAFETY
INFORMATION
IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
Gastrointestinal Adverse Reactions
- KRAZATI can cause severe gastrointestinal adverse
reactions.
- Monitor and manage patients using supportive care, including
antidiarrheals, antiemetics, or fluid replacement, as indicated.
Withhold, reduce the dose, or permanently discontinue KRAZATI based
on severity.
QTc Interval Prolongation
- KRAZATI can cause QTc interval prolongation, which can increase
the risk for ventricular tachyarrhythmias (eg, torsades de pointes)
or sudden death.
- Avoid concomitant use of KRAZATI with other products with a
known potential to prolong the QTc interval. Avoid use of KRAZATI
in patients with congenital long QT syndrome and in patients with
concurrent QTc prolongation.
- Monitor ECGs and electrolytes, particularly potassium and
magnesium, prior to starting KRAZATI, during concomitant use, and
as clinically indicated in patients with congestive heart failure,
bradyarrhythmias, electrolyte abnormalities, and in patients who
are unable to avoid concomitant medications that are known to
prolong the QT interval. Correct electrolyte abnormalities.
Withhold, reduce the dose, or permanently discontinue KRAZATI,
depending on severity.
Hepatotoxicity
- KRAZATI can cause hepatotoxicity, which may lead to
drug-induced liver injury and hepatitis.
- Monitor liver laboratory tests (AST, ALT, alkaline phosphatase,
and total bilirubin) prior to the start of KRAZATI, and monthly for
3 months or as clinically indicated, with more frequent testing in
patients who develop transaminase elevations. Reduce the dose,
withhold, or permanently discontinue KRAZATI based on
severity.
Interstitial Lung Disease/Pneumonitis
- KRAZATI can cause interstitial lung disease (ILD)/pneumonitis,
which can be fatal.
- Monitor patients for new or worsening respiratory symptoms
indicative of ILD/pneumonitis (eg, dyspnea, cough, fever) during
treatment with KRAZATI. Withhold KRAZATI in patients with suspected
ILD/pneumonitis and permanently discontinue KRAZATI if no other
potential causes of ILD/pneumonitis are identified.
ADVERSE REACTIONS
- Serious adverse reactions occurred in 57% of 116 patients who
received adagrasib in NSCLC patients. The most common adverse
reactions in NSCLC patients (≥20%) were diarrhea, nausea, fatigue,
vomiting, musculoskeletal pain, hepatotoxicity, renal impairment,
dyspnea, edema, decreased appetite, cough, pneumonia, dizziness,
constipation, abdominal pain, and QTc interval prolongation.
- Serious adverse reactions occurred in 30% of 94 patients who
received adagrasib in combination with cetuximab. The most common
adverse reactions in CRC patients (≥20%) were rash, nausea,
diarrhea, vomiting, fatigue, musculoskeletal pain, hepatotoxicity,
headache, dry skin, abdominal pain, decreased appetite, edema,
anemia, dizziness, cough, constipation, and peripheral
neuropathy.
DRUG INTERACTIONS
- Strong CYP3A4 Inducers: Avoid concomitant use.
- Strong CYP3A4 Inhibitors: Avoid concomitant use until adagrasib
concentrations have reached steady state (after ~8 days).
- Sensitive CYP3A4 Substrates: Avoid concomitant use with
sensitive CYP3A4 substrates.
- Sensitive CYP2C9 or CYP2D6 Substrates or P-gp Substrates: Avoid
concomitant use with sensitive CYP2C9 or CYP2D6 substrates or P-gp
substrates where minimal concentration changes may lead to serious
adverse reactions.
- Drugs That Prolong QT Interval: Avoid concomitant use with
KRAZATI.
Please see Drug Interactions Section of the Full Prescribing
Information for additional information.
USE IN SPECIFIC POPULATIONS
Females and Males of Reproductive Potential
- Infertility: Based on findings from animal studies, KRAZATI may
impair fertility in females and males of reproductive
potential.
Lactation
- Advise not to breastfeed.
Please see U.S. Full Prescribing
Information for KRAZATI.
Bristol Myers Squibb: Creating a Better
Future for People with Cancer
Bristol Myers Squibb is inspired by a single vision —
transforming patients’ lives through science. The goal of the
company’s cancer research is to deliver medicines that offer each
patient a better, healthier life and to make cure a possibility.
Building on a legacy across a broad range of cancers that have
changed survival expectations for many, Bristol Myers Squibb
researchers are exploring new frontiers in personalized medicine
and, through innovative digital platforms, are turning data into
insights that sharpen their focus. Deep understanding of causal
human biology, cutting-edge capabilities and differentiated
research platforms uniquely position the company to approach cancer
from every angle.
Cancer can have a relentless grasp on many parts of a patient’s
life, and Bristol Myers Squibb is committed to taking actions to
address all aspects of care, from diagnosis to survivorship. As a
leader in cancer care, Bristol Myers Squibb is working to empower
all people with cancer to have a better future.
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, please visit BMS.com or
follow us on LinkedIn, X (formerly Twitter), YouTube, Facebook, and
Instagram.
Cautionary Statement Regarding
Forward-Looking Statements
This press release contains “forward-looking statements” within
the meaning of the Private Securities Litigation Reform Act of 1995
regarding, among other things, the research, development and
commercialization of pharmaceutical products. All statements that
are not statements of historical facts are, or may be deemed to be,
forward-looking statements. Such forward-looking statements are
based on current expectations and projections about our future
financial results, goals, plans and objectives and involve inherent
risks, assumptions and uncertainties, including internal or
external factors that could delay, divert or change any of them in
the next several years, that are difficult to predict, may be
beyond our control and could cause our future financial results,
goals, plans and objectives to differ materially from those
expressed in, or implied by, the statements. These risks,
assumptions, uncertainties and other factors include, among others,
whether KRAZATI (adagrasib) in combination with cetuximab for the
additional indication described in this release will be
commercially successful, that any marketing approvals, if granted,
may have significant limitations on their use, and that continued
approval of KRAZATI in combination with cetuximab for such
additional indication described in this release may be contingent
upon verification and description of clinical benefit in
confirmatory trials. No forward-looking statement can be
guaranteed. Forward-looking statements in this press release should
be evaluated together with the many risks and uncertainties that
affect Bristol Myers Squibb’s business and market, particularly
those identified in the cautionary statement and risk factors
discussion in Bristol Myers Squibb’s Annual Report on Form 10-K for
the year ended December 31, 2023, as updated by our subsequent
Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and
other filings with the Securities and Exchange Commission. The
forward-looking statements included in this document are made only
as of the date of this document and except as otherwise required by
applicable law, Bristol Myers Squibb undertakes no obligation to
publicly update or revise any forward-looking statement, whether as
a result of new information, future events, changed circumstances
or otherwise.
1 KRAZATI. Prescribing Information. Princeton, NJ. Mirati
Therapeutics, Inc., a Bristol Myers Squibb company; 2024. 2 Yaeger,
R., Weiss, et al. Adagrasib with or without cetuximab in colorectal
cancer with mutated KRAS G12C. New England Journal of Medicine.
2023;388(1), 44–54. https://doi.org/10.1056/nejmoa2212419 3 Prager,
G., et al. Trifluridine–Tipiracil and Bevacizumab in Refractory
Metastatic Colorectal Cancer. New England Journal of Medicine. 2023
May 4;388(18). https://www.nejm.org/doi/full/10.1056/NEJMoa2214963
4 Grothey, A., et al. Regorafenib monotherapy for previously
treated metastatic colorectal cancer (CORRECT): an international,
multicentre, randomised, placebo-controlled, phase 3 trial. Lancet.
https://pubmed.ncbi.nlm.nih.gov/23177514/ 5 What is colorectal
cancer? American Cancer Society. (n.d.)
https://www.cancer.org/cancer/colon-rectal-cancer/about/what-is-colorectal-cancer.html
6 Globocan 2020, World
https://gco.iarc.fr/today/data/factsheets/populations/900-world-fact-sheets.pdf
7 Colorectal cancer statistics: How common is colorectal cancer?
American Cancer Society. (n.d.).
https://www.cancer.org/cancer/types/colon-rectal-cancer/about/key-statistics.html
8 Hallin J, Engstrom LD, Hargis L, et al. The KRAS Inhibitor
MRTX849 Provides Insight toward Therapeutic Susceptibility of
KRAS-Mutant Cancers in Mouse Models and Patients. Cancer Discov.
2020;10(1):54-71 9 Campbell et al, Nature Genetics 2016 “Distinct
patterns of somatic genome alterations in lung adenocarcinomas 10
Nassar, A., et al. Distribution of KRASG12C Somatic Mutations
across Race, Sex, and Cancer Type. New England Journal of Medicine,
384:185-187. https://doi.org/10.1056/nejmc2030638
corporatefinancial-news
View source
version on businesswire.com: https://www.businesswire.com/news/home/20240621519236/en/
Bristol Myers Squibb Media Inquiries:
media@bms.com Investors: investor.relations@bms.com
Bristol Myers Squibb (NYSE:BMY)
Gráfica de Acción Histórica
De May 2024 a Jun 2024
Bristol Myers Squibb (NYSE:BMY)
Gráfica de Acción Histórica
De Jun 2023 a Jun 2024
