Bristol Myers Squibb Announces Pivotal
KRYSTAL-12 Confirmatory Trial Evaluating KRAZATI (adagrasib) Meets
Primary Endpoint of Progression-Free Survival for Patients with
Pretreated KRASG12C-Mutated Locally Advanced or Metastatic
Non-Small Cell Lung Cancer
Bristol Myers Squibb (NYSE: BMY) today announced that the
pivotal Phase 3 KRYSTAL-12 study, evaluating KRAZATI® (adagrasib)
as a monotherapy in patients with pretreated locally advanced or
metastatic non-small cell lung cancer (NSCLC) harboring a KRASG12C
mutation, met the primary endpoint of progression-free survival
(PFS) and the key secondary endpoint of overall response rate (ORR)
as assessed by Blinded Independent Central Review (BICR) at final
analysis for these endpoints. The study remains ongoing to assess
the additional key secondary endpoint of overall survival. Results
of the confirmatory trial showed that KRAZATI demonstrated a
statistically significant and clinically meaningful benefit in PFS
and ORR compared to standard-of-care chemotherapy as a second-line
or later treatment for these patients. KRAZATI had no new safety
signals and the safety data was consistent with the known safety
profile.
“Today’s news is an important reinforcement of the power of a
targeted therapy for patients with locally advanced or metastatic
KRASG12C-mutated lung cancer. FDA approval of KRAZATI in the U.S.
has allowed us to provide a new treatment option for these
patients, and topline results of the KRYSTAL-12 confirmatory study
will build greater trust in the medical and patient community,”
said Abderrahim Oukessou, M.D., vice president, global program
lead, KRAZATI, Bristol Myers Squibb. “We are encouraged by the
results from KRYSTAL-12 and look forward to helping more patients
with KRASG12C-mutated lung cancer.”
The company will complete a full evaluation of the available
data and looks forward to sharing the results with the scientific
community at an upcoming medical conference as well as discussing
the results with health authorities.
The U.S. FDA granted accelerated approval for KRAZATI as a
targeted treatment for patients with KRASG12C-mutated locally
advanced or metastatic NSCLC who have received at least one prior
systemic therapy in December 2022. In 2023, Medicines and
Healthcare products Regulatory Agency (MHRA) granted conditional
marketing authorization for KRAZATI as a targeted treatment option
for adult patients with KRASG12C-mutated advanced NSCLC and disease
progression after at least one prior systemic therapy followed by
the European Commission (EC) in 2024.
In addition to KRASG12C-mutated NSCLC, KRAZATI and KRAZATI-based
combinations have shown encouraging meaningful benefit in Phase 2
clinical trials across several tumors, including advanced
colorectal cancer, pancreatic cancer and other solid tumors. In
February, the U.S. FDA accepted for priority review the
supplemental new drug application (sNDA) for KRAZATI in combination
with cetuximab for the treatment of patients with previously
treated KRASG12C-mutated locally advanced or metastatic colorectal
cancer (CRC). The FDA assigned a Prescription Drug User Fee Act
(PDUFA) goal date of June 21, 2024.
Bristol Myers Squibb thanks the patients and investigators
involved in the KRYSTAL-12 clinical trial.
ABOUT KRAZATI®
(adagrasib)
KRAZATI (adagrasib) is 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 KRAS protein regenerates every
24-48 hours. KRASG12C mutations act as oncogenic drivers and occur
in approximately 14% of non-small cell lung cancer, 3-4% of
colorectal cancer, and 1-2% of several other cancers.
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(s).
In 2023, Medicines and Healthcare products Regulatory Agency
(MHRA) granted conditional marketing authorization for KRAZATI as a
targeted treatment option for adult patients with KRASG12C-mutated
advanced non-small cell lung cancer and disease progression after
at least one prior systemic therapy followed by the European
Commission (EC) in 2024.
KRAZATI continues to be evaluated as monotherapy and in
combination with other anti-cancer therapies in patients with
advanced KRASG12C-mutated solid tumors, including non-small cell
lung cancer and colorectal cancer.
In 2022, the FDA granted breakthrough therapy designation for
KRAZATI in combination with cetuximab in patients with
KRASG12C-mutated advanced colorectal cancer whose cancer has
progressed following prior treatment with chemotherapy and an
anti-VEGF therapy.
For Prescribing Information, visit KRAZATI.
About KRYSTAL-12
KRYSTAL-12 is an open-label, multicenter, randomized Phase 3
study evaluating KRAZATI compared to standard-of-care chemotherapy
alone, in patients with KRASG12C-mutated non-small cell lung
cancer. The primary endpoint of the study is PFS as assessed by
BICR. Secondary endpoints included overall survival (OS), overall
response rate (ORR), duration of response (DOR), and safety.
INDICATION
KRAZATI is indicated for the treatment of adult patients with
KRASG12C-mutated locally advanced or metastatic non-small cell lung
cancer, 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(s).
IMPORTANT SAFETY
INFORMATION
GASTROINTESTINAL ADVERSE REACTIONS
- In the pooled safety population, serious gastrointestinal
adverse reactions observed were gastrointestinal obstruction in
1.6%, including 1.4% grade 3 or 4, gastrointestinal bleeding in
0.5% of patients, including 0.5% grade 3, and colitis in 0.3%,
including 0.3% grade 3. In addition, nausea, diarrhea, or vomiting
occurred in 89% of 366 patients, including 9% grade 3. Nausea,
diarrhea, or vomiting led to dosage interruption or dose reduction
in 29% of patients and permanent discontinuation of KRAZATI in
0.3%
- 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
- In the pooled safety population, 6% of 366 patients with at
least one post-baseline electrocardiogram (ECG) assessment had an
average QTc ≥501 ms, and 11% of patients had an increase from
baseline of QTc >60 msec. KRAZATI causes concentration-dependent
increases in the QTc interval
- 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 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 taking medications that are
known to prolong the QT interval. Withhold, reduce the dose, or
permanently discontinue KRAZATI, depending on severity
HEPATOTOXICITY
- KRAZATI can cause hepatotoxicity
- In the pooled safety population, hepatotoxicity occurred in
37%, and 7% were grade 3 or 4. A total of 32% of patients who
received KRAZATI had increased alanine aminotransferase
(ALT)/increased aspartate aminotransferase (AST); 5% were grade 3
and 0.5% were grade 4. Increased ALT/AST leading to dose
interruption or reduction occurred in 11% of patients. KRAZATI was
discontinued due to increased ALT/AST in 0.5% of patients
- 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. In the pooled safety population,
ILD/pneumonitis occurred in 4.1% of patients, 1.4% were grade 3 or
4, and 1 case was fatal. The median time to first onset for
ILD/pneumonitis was 12 weeks (range: 5 to 31 weeks). KRAZATI was
discontinued due to ILD/pneumonitis in 0.8% of patients
- Monitor patients for new or worsening respiratory symptoms
indicative of ILD/pneumonitis (eg, dyspnea, cough, fever). Withhold
KRAZATI in patients with suspected ILD/pneumonitis and permanently
discontinue KRAZATI if no other potential causes of ILD/pneumonitis
are identified
ADVERSE REACTIONS
- The most common adverse reactions (≥25%) are nausea, diarrhea,
vomiting, fatigue, musculoskeletal pain, hepatotoxicity, renal
impairment, edema, dyspnea, decreased appetite
FEMALES AND MALES OF REPRODUCTIVE POTENTIAL
- Infertility: Based on findings from animal studies, KRAZATI may
impair fertility in females and males of reproductive
potential
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 programs 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, visit us at BMS.com or
follow us on LinkedIn, 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,
that results of future post-marketing studies will not be
consistent with the results of this study, that KRAZATI (adagrasib)
may not be commercially successful, that any marketing approvals,
if granted, may have significant limitations on their use, and,
that continued approval of Krazati may be contingent upon
verification and description of clinical benefit in additional
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.
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