FDA Has Issued New Postmarketing
Requirement
LUMAKRAS Dosing Confirmed at 960 mg Once-Daily
for Patients With KRAS G12C-Mutated NSCLC Under Accelerated
Approval
THOUSAND
OAKS, Calif., Dec. 26,
2023 /PRNewswire/ -- Amgen (NASDAQ:AMGN) announced
today that the U.S. Food and Drug Administration (FDA) has
completed its review of the company's supplemental New Drug
Application seeking full approval of LUMAKRAS®
(sotorasib). This review, which resulted in a Complete
Response Letter, was based on the CodeBreaK 200 trial
results for the treatment of adults with previously treated
locally advanced or metastatic KRAS G12C-mutated
non-small cell lung cancer (NSCLC). The FDA also issued a new
postmarketing requirement (PMR) for an additional confirmatory
study to support full approval that will be completed no later than
February 2028.
In addition, the FDA concluded that the dose comparison PMR
issued at the time of LUMAKRAS accelerated approval, to compare the
safety and efficacy of LUMAKRAS 960 mg daily dose versus a lower
daily dose, has been fulfilled. The company said LUMAKRAS at 960 mg
once-daily will remain the dose for patients with KRAS
G12C-mutated NSCLC under accelerated approval.
In May 2021, LUMAKRAS was the
first KRASG12C inhibitor to receive regulatory
approval in the U.S., under accelerated approval. To date,
over 15,000 patients worldwide have received LUMAKRAS/LUMYKRAS
through the clinical development program, early access and
commercial use.
About Advanced Non-Small Cell Lung Cancer and
the KRAS G12C Mutation
Lung cancer is the
leading cause of cancer-related deaths worldwide, and it accounts
for more deaths worldwide than colon cancer, breast cancer and
prostate cancer combined.1
KRAS G12C is the most
common KRAS mutation in
NSCLC.2 About 13% of patients with non-squamous
NSCLC harbor the KRAS G12C
mutation.3 Unmet medical need remains high and
treatment options are limited for NSCLC patients with
the KRAS G12C mutation whose first-line treatment
has failed to work or has stopped working.
LUMAKRAS® (sotorasib) U.S. Indication
LUMAKRAS is indicated for the treatment of adult patients
with KRAS G12C-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
overall response rate (ORR) and duration of response (DOR).
Continued approval for this indication may be contingent upon
verification and description of clinical benefit in a confirmatory
trial(s).
LUMAKRAS® (sotorasib)
Important U.S. Safety Information
Hepatotoxicity
- LUMAKRAS can cause hepatotoxicity, which may lead to
drug-induced liver injury and hepatitis.
- Among 357 patients who received LUMAKRAS in CodeBreaK 100,
hepatotoxicity occurred in 1.7% (all grades) and 1.4% (Grade 3). A
total of 18% of patients who received LUMAKRAS had increased
alanine aminotransferase (ALT)/increased aspartate aminotransferase
(AST); 6% were Grade 3 and 0.6% were Grade 4. In addition to dose
interruption or reduction, 5% of patients received corticosteroids
for the treatment of hepatotoxicity.
- Monitor liver function tests (ALT, AST and total bilirubin)
prior to the start of LUMAKRAS every 3 weeks for the first 3 months
of treatment, then once a month or as clinically indicated, with
more frequent testing in patients who develop transaminase and/or
bilirubin elevations.
- Withhold, dose reduce or permanently discontinue LUMAKRAS based
on severity of adverse reaction.
Interstitial Lung Disease (ILD)/Pneumonitis
- LUMAKRAS can cause ILD/pneumonitis that can be fatal. Among 357
patients who received LUMAKRAS in CodeBreaK 100, ILD/pneumonitis
occurred in 0.8% of patients, all cases were Grade 3 or 4 at onset,
and 1 case was fatal. LUMAKRAS was discontinued due to
ILD/pneumonitis in 0.6% of patients.
- Monitor patients for new or worsening pulmonary symptoms
indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever).
Immediately withhold LUMAKRAS in patients with suspected
ILD/pneumonitis and permanently discontinue LUMAKRAS if no other
potential causes of ILD/pneumonitis are identified.
Most Common Adverse Reactions
- The most common adverse reactions occurring in ≥ 20% were
diarrhea, musculoskeletal pain, nausea, fatigue, hepatotoxicity and
cough.
Drug Interactions
- Advise patients to inform their healthcare provider of all
concomitant medications, including prescription medicines,
over-the-counter drugs, vitamins, dietary and herbal products.
- Inform patients to avoid proton pump inhibitors and
H2 receptor antagonists while taking LUMAKRAS.
- If coadministration with an acid-reducing agent cannot be
avoided, inform patients to take LUMAKRAS 4 hours before or 10
hours after a locally acting antacid.
Please see LUMAKRAS full Prescribing Information.
About Amgen
Amgen is committed to unlocking the potential of biology for
patients suffering from serious illnesses by discovering,
developing, manufacturing and delivering innovative human
therapeutics. This approach begins by using tools like advanced
human genetics to unravel the complexities of disease and
understand the fundamentals of human biology.
Amgen focuses on areas of high unmet medical need and
leverages its expertise to strive for solutions that improve health
outcomes and dramatically improve people's lives. A biotechnology
pioneer since 1980, Amgen has grown to be one
of the world's leading independent biotechnology
companies, has reached millions of patients around the world and is
developing a pipeline of medicines with breakaway
potential.
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__________________________________
1 Sung H, et al. CA Cancer J Clin.
2021;71:209-249.
2 Arbour KC, et al. Clin
Cancer Res. 2018;24:334-340.
3 Nassar AF, et al. N Engl J. Med.
2021;384:185-187.
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