INDICATIONS
AND USAGE
LIBTAYO is a programmed death receptor-1 (PD-1) blocking antibody indicated:
Advanced Cutaneous Squamous Cell Carcinoma (CSCC)
Advanced Basal Cell Carcinoma (BCC)
Advanced Non-Small Cell Lung Cancer (NSCLC)
DOSAGE AND
ADMINISTRATION
The recommended
dosage of LIBTAYO is 350 mg administered as an intravenous infusion over 30 minutes every 3
weeks until disease progression or unacceptable toxicity.
DOSAGE FORMS
AND STRENGTHS
Injection: 350 mg/7 mL (50 mg/mL) solution in a single-dose vial
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All rights reserved. LIB.22.04.0050 05/2022
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Important Safety Information and Indications
LIBTAYO is a programmed death receptor-1 (PD-1) blocking antibody indicated:
• for the treatment of patients with metastatic cutaneous squamous cell carcinoma (mCSCC) or locally advanced CSCC (laCSCC) who are not candidates for curative surgery or curative radiation.
• for the treatment of patients with locally advanced BCC (laBCC) previously treated with a hedgehog pathway inhibitor or for whom a hedgehog pathway inhibitor is not appropriate.
• for
the first-line treatment of patients with NSCLC whose tumors have high PD-L1
expression [Tumor Proportion Score (TPS) ≥ 50%] as determined by an FDA-approved
test, with no EGFR, ALK or ROS1 aberrations, and is:
• locally advanced where patients are not
candidates for surgical resection or definitive chemoradiation
or
• metastatic.
Important Safety Information
Warnings and
Precautions
Severe and Fatal Immune-Mediated Adverse Reactions
Immune-mediated
adverse reactions, which may be severe or fatal, can occur in any organ system
or tissue at any time after starting treatment. While immune-mediated adverse
reactions usually occur during treatment, they can also occur after
discontinuation. Immune-mediated adverse reactions affecting more than one body
system can occur simultaneously. Early identification and management are
essential to ensuring safe use of PD-1/PD-L1–blocking antibodies. The
definition of immune-mediated adverse reactions included the required use of
systemic corticosteroids or other immunosuppressants and the absence of a clear
alternate etiology. Monitor closely for symptoms and signs that may be clinical
manifestations of underlying immune-mediated adverse reactions. Evaluate liver
enzymes, creatinine, and thyroid function at baseline and periodically during
treatment. In cases of suspected immune-mediated adverse reactions, initiate
appropriate workup to exclude alternative etiologies, including infection. Institute
medical management promptly, including specialty consultation as appropriate.
No dose
reduction for LIBTAYO is recommended. In general, withhold LIBTAYO for severe
(Grade 3) immune-mediated adverse reactions. Permanently discontinue LIBTAYO
for life-threatening (Grade 4) immune-mediated adverse reactions, recurrent
severe (Grade 3) immune-mediated adverse reactions that require systemic
immunosuppressive treatment, or an inability to reduce corticosteroid dose to
10 mg or less of prednisone equivalent per day within 12 weeks of initiating
steroids.
Withhold or
permanently discontinue LIBTAYO depending on severity. In general, if LIBTAYO
requires interruption or discontinuation, administer systemic corticosteroid
therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade
1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and
continue to taper over at least 1 month. Consider administration of other
systemic immunosuppressants in patients whose immune-mediated adverse reactions
are not controlled with corticosteroids.
Immune-mediated pneumonitis: LIBTAYO can cause immune-mediated
pneumonitis. In patients treated with other PD-1/PD-L1–blocking antibodies, the
incidence of pneumonitis is higher in patients who have received prior thoracic
radiation. Immune-mediated pneumonitis occurred in 3.2% (26/810) of patients
receiving LIBTAYO, including Grade 4 (0.5%), Grade 3 (0.5%), and Grade 2 (2.1%).
Pneumonitis led to permanent discontinuation in 1.4% of patients and
withholding of LIBTAYO in 2.1% of patients. Systemic corticosteroids were
required in all patients with pneumonitis. Pneumonitis resolved in 58% of the 26
patients. Of the 17 patients in whom LIBTAYO was withheld, 9 reinitiated after
symptom improvement; of these, 3/9 (33%) had recurrence of pneumonitis.
Withhold LIBTAYO for Grade 2, and permanently discontinue for Grade 3 or 4.
Resume in patients with complete or partial resolution (Grade 0 to 1) after
corticosteroid taper. Permanently discontinue if no complete or partial
resolution within 12 weeks of initiating steroids or inability to reduce
prednisone to less than 10 mg per day (or equivalent) within 12 weeks of
initiating steroids.
Immune-mediated colitis: LIBTAYO can cause immune-mediated
colitis. The primary component of immune-mediated colitis was diarrhea.
Cytomegalovirus (CMV) infection/reactivation has been reported in patients with
corticosteroid-refractory immune-mediated colitis treated with PD-1/PD-L1–blocking
antibodies. In cases of corticosteroid-refractory immune-mediated colitis,
consider repeating infectious workup to exclude alternative etiologies.
Immune-mediated colitis occurred in 2.2% (18/810) of patients receiving
LIBTAYO, including Grade 3 (0.9%) and Grade 2 (1.1%). Colitis led to permanent
discontinuation in 0.4% of patients and withholding of LIBTAYO in 1.5% of
patients. Systemic corticosteroids were required in all patients with colitis.
Colitis resolved in 39% of the 18 patients. Of the 12 patients in whom LIBTAYO
was withheld, 4 reinitiated LIBTAYO after symptom improvement; of these, 3/4
(75%) had recurrence. Withhold LIBTAYO for Grade 2 or 3, and permanently
discontinue for Grade 4. Resume in patients with complete or partial resolution
(Grade 0 to 1) after corticosteroid taper. Permanently discontinue if no
complete or partial resolution within 12 weeks of initiating steroids or
inability to reduce prednisone to less than 10 mg per day (or equivalent)
within 12 weeks of initiating steroids.
Immune-mediated hepatitis: LIBTAYO can cause immune-mediated
hepatitis. Immune-mediated hepatitis occurred in 2% (16/810) of patients
receiving LIBTAYO, including fatal (0.1%), Grade 4 (0.1%), Grade 3 (1.4%), and
Grade 2 (0.2%). Hepatitis led to permanent discontinuation of LIBTAYO in 1.2%
of patients and withholding of LIBTAYO in 0.5% of patients. Systemic
corticosteroids were required in all patients with hepatitis. Additional
immunosuppression with mycophenolate was required in 19% (3/16) of these
patients. Hepatitis resolved in 50% of the 16 patients. Of the 5 patients in
whom LIBTAYO was withheld, 3 reinitiated LIBTAYO after symptom improvement; of
these, none had recurrence.
For
hepatitis with no tumor involvement of the liver: Withhold LIBTAYO if AST or ALT
increases to more than 3 and up to 8 times the upper limit of normal (ULN) or
if total bilirubin increases to more than 1.5 and up to 3 times the ULN.
Permanently discontinue LIBTAYO if AST or ALT increases to more than 8 times
the ULN or total bilirubin increases to more than 3 times the ULN.
For
hepatitis with tumor involvement of the liver: Withhold LIBTAYO if baseline AST or ALT is more than 1
and up to 3 times ULN and increases to more than 5 and up to 10 times ULN. Also,
withhold LIBTAYO if baseline AST or ALT is more than 3 and up to 5 times ULN
and increases to more than 8 and up to 10 times ULN. Permanently discontinue
LIBTAYO if AST or ALT increases to more than 10 times ULN or if total bilirubin
increases to more than 3 times ULN. If AST and ALT are less than or equal to
ULN at baseline, withhold or permanently discontinue LIBTAYO based on
recommendations for hepatitis with no liver involvement.
Resume in
patients with complete or partial resolution (Grade 0 to 1) after
corticosteroid taper. Permanently discontinue if no complete or partial
resolution within 12 weeks of initiating steroids or inability to reduce
prednisone to less than 10 mg per day (or equivalent) within 12 weeks of
initiating steroids.
Immune-mediated endocrinopathies: For Grade 3 or 4 endocrinopathies,
withhold until clinically stable or permanently discontinue depending on
severity.
Immune-mediated nephritis with renal
dysfunction: LIBTAYO
can cause immune-mediated nephritis. Immune-mediated nephritis occurred in 0.6%
(5/810) of patients receiving LIBTAYO, including fatal (0.1%), Grade 3 (0.1%),
and Grade 2 (0.4%). Nephritis led to permanent discontinuation in 0.1% of
patients and withholding of LIBTAYO in 0.4% of patients. Systemic
corticosteroids were required in all patients with nephritis. Nephritis
resolved in 80% of the 5 patients. Of the 3 patients in whom LIBTAYO was
withheld, 2 reinitiated LIBTAYO after symptom improvement; of these, none had
recurrence. Withhold LIBTAYO for Grade 2 or 3 increased blood creatinine, and
permanently discontinue for Grade 4 increased blood creatinine. Resume in
patients with complete or partial resolution (Grade 0 to 1) after
corticosteroid taper. Permanently discontinue if no complete or partial
resolution within 12 weeks of initiating steroids or inability to reduce
prednisone to less than 10 mg per day (or equivalent) within 12 weeks of
initiating steroids.
Immune-mediated dermatologic adverse
reactions: LIBTAYO can
cause immune-mediated rash or dermatitis. Exfoliative dermatitis, including
Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug rash
with eosinophilia and systemic symptoms (DRESS) has occurred with PD-1/PD-L1–blocking
antibodies. Immune-mediated dermatologic adverse reactions occurred in 1.6% (13/810)
of patients receiving LIBTAYO, including Grade 3 (0.9%) and Grade 2 (0.6%). Immune-mediated
dermatologic adverse reactions led to permanent discontinuation in 0.1% of
patients and withholding of LIBTAYO in 1.4% of patients. Systemic
corticosteroids were required in all patients with immune-mediated dermatologic
adverse reactions. Immune-mediated dermatologic adverse reactions resolved in 69%
of the 13 patients. Of the 11 patients in whom LIBTAYO was withheld for
dermatologic adverse reactions, 7 reinitiated LIBTAYO after symptom
improvement; of these, 43% (3/7) had recurrence of the dermatologic adverse
reaction. Topical emollients and/or topical corticosteroids may be adequate to
treat mild to moderate non-exfoliative rashes. Withhold LIBTAYO for suspected
SJS, TEN, or DRESS. Permanently discontinue LIBTAYO for confirmed SJS, TEN, or
DRESS. Resume in patients with complete or partial resolution (Grade 0 to 1)
after corticosteroid taper. Permanently discontinue if no complete or partial
resolution within 12 weeks of initiating steroids or inability to reduce
prednisone to less than 10 mg per day (or equivalent) within 12 weeks of
initiating steroids.
Other immune-mediated adverse reactions: The following clinically significant
immune-mediated adverse reactions occurred at an incidence of <1% in 810
patients who received LIBTAYO or were reported with the use of other PD-1/PD-L1–blocking
antibodies. Severe or fatal cases have been reported for some of these adverse
reactions.
Infusion-related reactions
Severe
infusion-related reactions (Grade 3) occurred in 0.1% of patients receiving
LIBTAYO as a single agent. Monitor patients for signs and symptoms of
infusion-related reactions. The most common symptoms of infusion-related
reaction were nausea, pyrexia, rash, and dyspnea. Interrupt or slow the rate of
infusion for Grade 1 or 2, and permanently discontinue for Grade 3 or 4.
Complications of allogeneic HSCT
Fatal and other
serious complications can occur in patients who receive allogeneic
hematopoietic stem cell transplantation (HSCT) before or after being treated
with a PD-1/PD-L1–blocking antibody. Transplant-related complications include
hyperacute graft-versus-host disease (GVHD), acute GVHD, chronic GVHD, hepatic
veno-occlusive disease (VOD) after reduced intensity conditioning, and steroid-requiring
febrile syndrome (without an identified infectious cause). These complications
may occur despite intervening therapy between PD-1/PD-L1 blockade and
allogeneic HSCT. Follow patients closely for evidence of transplant-related
complications and intervene promptly. Consider the benefit versus risks of
treatment with a PD-1/PD-L1–blocking antibody prior to or after an allogeneic
HSCT.
Embryo-fetal toxicity
LIBTAYO can
cause fetal harm when administered to a pregnant woman due to an increased risk
of immune-mediated rejection of the developing fetus resulting in fetal death.
Advise women of the potential risk to a fetus. Advise females of reproductive
potential to use effective contraception during treatment with LIBTAYO and for
at least 4 months after the last dose.
Adverse Reactions
Use in Specific
Populations