Late-breaking data to be featured in an oral
presentation at the American Association for Cancer Research (AACR)
annual meeting on Monday, April 8 and highlighted as part of the
official meeting press program
Bristol Myers Squibb (NYSE: BMY) today announced data from the
cohorts of the Phase 1/ 2 KRYSTAL-1 study evaluating KRAZATI®
(adagrasib) in combination with cetuximab for the treatment of
patients with previously treated KRASG12C-mutated locally advanced
or metastatic colorectal cancer (CRC).
These late breaking data (abstract #CT013) will be featured in
an oral presentation at the 2024 American Association for Cancer
Research (AACR) annual meeting on Monday, April 8 at 11:10 a.m.
Pacific Time and will be highlighted as part of the meeting’s
official press program. The data will also be published
simultaneously in Cancer Discovery.
With a median follow up of 11.9 months in 94 patients, KRAZATI
plus cetuximab demonstrated an objective response rate, the primary
endpoint, of 34%, median progression-free survival of 6.9 months
(95% CI, 5.7-7.4), and median overall survival of 15.9 months (95%
CI, 11.8-18.8) in pre-treated patients with KRASG12C-mutated
locally advanced or metastatic CRC. The median duration of response
was 5.8 months. Disease control was observed in 85% of patients.
The safety profile for KRAZATI plus cetuximab was manageable and
consistent with previous reports, and with the known safety profile
of each drug individually.
KRASG12C mutations act as oncogenic drivers and occur in
approximately 3-4% of colorectal cancers. In previous studies,
treatment with cetuximab as a single agent did not offer a clinical
benefit in patients with KRAS-mutated colorectal cancer.
“Patients with KRASG12C-mutated colorectal cancer have
historically faced poor prognoses and remain in need of additional
treatment options,” said Scott Kopetz, M.D., Ph.D, FACP, associate
vice president for translational research, and Professor,
Department of Gastrointestinal Medical Oncology at The University
of Texas MD Anderson Cancer Center. “Although KRAS had previously
been considered ‘undruggable,’ these data from KRYSTAL-1 reinforce
the potential benefit of adagrasib for these specific
patients.”
“While there has been progress in the treatment of colorectal
cancer, there remain groups of patients, such as those with
KRAS-mutated cancers, who continue to need new, targeted treatment
options,” said Anne Kerber, senior vice president, head of late
clinical development, Hematology, Oncology, Cell Therapy (HOCT) at
Bristol Myers Squibb. “These data highlight the significance of
testing and identification of KRASG12C mutations in patients with
CRC.”
The company announced in February 2024 that the FDA had accepted
a supplemental new drug application for KRAZATI in combination with
cetuximab as a targeted treatment option for patients with
previously treated KRASG12C-mutated locally advanced or metastatic
CRC for priority review and 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-1 clinical trial.
This study was funded by Mirati Therapeutics, Inc., a Bristol
Myers Squibb company. KRAZATI is a registered trademark of Mirati
Therapeutics, Inc., a Bristol Myers Squibb company.
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 KRASG12C protein regenerates every
24-48 hours. KRASG12C mutations act as oncogenic drivers and occur
in approximately 14% of NSCLC (adenocarcinoma), 3-4% of colorectal
cancers, 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 non-small cell lung cancer (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 2024, the European Commission (EC)
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.
KRAZATI continues to be evaluated as monotherapy and in
combination with other anti-cancer therapies in patients with
advanced KRASG12C-mutated solid tumors, including NSCLC 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 (CRC) whose cancer has
progressed following prior treatment with chemotherapy and an
anti-VEGF therapy.
For Prescribing Information, visit
https://mirati.com/KRAZATI_USPI/.
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 solid tumors that harbor a
KRASG12C mutation. The primary endpoint for the Phase 2 cohort of
the KRYSTAL-1 study was objective response rate. Secondary
endpoints included duration of response, progression-free survival,
overall survival and safety.
INDICATION
KRAZATI 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.
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 (e.g., 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 at
https://mirati.com/KRAZATI_USPI/.
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. CRC is the third most commonly diagnosed
cancer in the world. In 2020, it is estimated that there were
approximately 1,931,000 new cases of the disease; it is the second
leading cause of cancer-related deaths among men and women
combined.
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, 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 future study results may not be consistent with the results to
date, and that KRAZATI (adagrasib) in combination with cetuximab
may not achieve its primary study endpoint or KRAZATI (adagrasib)
in combination with cetuximab may not achieve its primary study
endpoint or receive regulatory approval for the additional
indication described in this release in the currently anticipated
timeline or at all, any marketing approvals, if granted, may have
significant limitations on their use, and, if approved, whether
such combination treatment for such additional indication described
in this release will be commercially successful. 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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