Posology : מינונים

4.2 Posology and method of administration

Treatment must be initiated and supervised by physicians experienced in the treatment of cancer.
Posology


Recommended dose
Cutaneous Squamous Cell Carcinoma
The recommended dose is 350 mg cemiplimab every 3 weeks (Q3W) administered as an intravenous infusion over 30 minutes.

Treatment may be continued until disease progression or unacceptable toxicity.

Alternatively, a dose of 3 mg/kg every 2 weeks administered as an intravenous infusion over 30 minutes may be considered according to the treating physician’s discretion.

Basal Cell Carcinoma
The recommended dose is 350 mg cemiplimab every 3 weeks (Q3W) administered as an intravenous infusion over 30 minutes.

Treatment may be continued until disease progression or unacceptable toxicity.

Dose modifications
No dose reductions are recommended. Dosing delay or discontinuation may be required based on individual safety and tolerability. Recommended modifications to manage adverse reactions are provided in Table 1.
Detailed guidelines for the management of immune-mediated adverse reactions are described in Table 1 (see also sections 4.4 and 4.8).


Table 1:         Recommended treatment modifications
Adverse reactiona          Severityb                  Dose modification            Additional intervention 
Immune-mediated adverse reactions

Initial dose of 1 to
2 mg/kg/day prednisone
Withhold LIBTAYO or equivalent followed by a taper
Grade 2
Pneumonitis                                           Resume LIBTAYO if pneumonitis improves and remains at Grade 0 to 1 after corticosteroid taper to
≤10 mg/day prednisone or equivalent

Initial dose of 2 to
Grade 3 or 4
4 mg/kg/day prednisone or                         Permanently discontinue or equivalent followed recurrent Grade 2 by a taper
Initial dose of 1 to
2 mg/kg/day prednisone
Withhold LIBTAYO or equivalent followed
Grade 2 or 3                                            by a taper
Colitis                                               Resume LIBTAYO if colitis or diarrhoea improves and remains at Grade 0 to 1 after corticosteroid taper to ≤10 mg/day prednisone or equivalent
Initial dose of 1 to
Grade
2 mg/kg/day prednisone
4 or                       Permanently discontinue      or equivalent followed by recurrent Grade 3                                       a taper
Grade 2 with AST or ALT                                  Initial dose of 1 to > 3 and ≤ 5×ULN             Withhold LIBTAYO             2 mg/kg/day prednisone or                                                      or equivalent followed by a taper

total bilirubin > 1.5 and     Resume LIBTAYO if hepatitis improves and remains Hepatitis                  ≤ 3×ULN                       at Grade 0 to 1 after corticosteroid taper to ≤ 10 mg/day prednisone or equivalent or returns to baseline AST or ALT after completion of corticosteroid taper
Grade ≥ 3 with AST or
Initial dose of 1 to
ALT > 5×ULN
2 mg/kg/day prednisone or
Permanently discontinue     or equivalent followed total bilirubin > 3×ULN by a taper
Initiate thyroid hormone
Withhold LIBTAYO            replacement as clinically
Hypothyroidism             Grade 3 or 4                                              indicated Resume LIBTAYO when hypothyroidism returns to
Grade 0 to 1 or is otherwise clinically stable

Initiate
Withhold LIBTAYO            symptomatic
Hyperthyroidism            Grade 3 or 4                                              management Resume LIBTAYO when hyperthyroidism returns to
Grade 0 to 1 or is otherwise clinically stable
Initiate
Withhold LIBTAYO            symptomatic management
Thyroiditis                Grade 3 to 4

Resume LIBTAYO when thyroiditis returns to
Grade 0 to 1 or is otherwise clinically stable

Initial dose of 1 to
2 mg/kg/day prednisone
Withhold LIBTAYO             or equivalent followed by a taper and hormone
Hypophysitis               Grade 2 to 4                                               replacement as clinically indicated
Resume LIBTAYO if hypophysitis improves and remains at Grade 0 to 1 after corticosteroid taper to
≤10 mg/day prednisone or equivalent or is otherwise clinically stable
Initial dose of 1 to
2 mg/kg/day prednisone or equivalent followed by
Withhold LIBTAYO a taper and hormone replacement as clinically
Adrenal insufficiency      Grade 2 to 4                                               indicated Resume LIBTAYO if adrenal insufficiency improves and remains at Grade 0 to 1 after corticosteroid taper to ≤10 mg/day prednisone or equivalent or is otherwise clinically stable
Initiate treatment with
Withhold LIBTAYO            anti-hyperglycaemics
Grade 3 or 4                                              as clinically indicated Type 1 diabetes mellitus
(hyperglycaemia)
Resume LIBTAYO when diabetes mellitus returns to
Grade 0 to 1 or is otherwise clinically stable
Grade 2 lasting longer than                               Initial dose of 1 to 1 week,                                                   2 mg/kg/day prednisone Withhold LIBTAYO
Grade 3                                                   or equivalent followed or                                                        by a taper
suspected Stevens-Johnson   Resume LIBTAYO if skin reaction improves Skin adverse reactions        syndrome (SJS) or toxic     and remains at Grade 0 to 1 after epidermal necrolysis        corticosteroid taper to ≤10 mg/day prednisone (TEN)                       or equivalent
Initial dose of 1 to
2 mg/kg/day prednisone
Grade 4 or confirmed SJS or TEN                      Permanently discontinue or equivalent followed by a taper
Initiate management immediately,
including initial dose of 1 to 2 mg/kg/day
Withhold LIBTAYO             prednisone or equivalent followed by a taper
Grade 2
Immune-mediated skin reaction or other immune-                                 Resume LIBTAYO if skin reaction or other mediated adverse reactions                                immune-mediated adverse reaction improves and in patients with prior                                    remains at Grade 0 to 1 after corticosteroid taper to treatment with idelalisib                                 ≤10 mg/day prednisone or equivalent Initiate management immediately,
including initial dose
Grade 3 or 4 (excluding     Permanently discontinue of 1 to 2 mg/kg/day endocrinopathies)                                        prednisone or or recurrent Grade 2                                     equivalent followed by a taper
Initial dose of 1 to
2 mg/kg/day prednisone
Withhold LIBTAYO or equivalent followed
Grade 2 creatinine                                       by a taper increased
Nephritis with renal                                      Resume LIBTAYO if nephritis improves and dysfunction                                               remains at Grade 0 to 1 after corticosteroid taper to ≤10 mg/day prednisone or equivalent
Initial dose of 1 to
Grade 3 or 4 creatinine                                  2 mg/kg/day prednisone Permanently discontinue increased                                                or equivalent followed by a taper
Other immune-mediated adverse reactions(including                                                            Initiate symptomatic but not limited to                                        Withhold LIBTAYO management paraneoplastic encephalomyelitis,
meningitis, myositis, solid organ transplant rejection,
graft-vs-host disease,
Guillain-Barre syndrome,
central nervous system
Grade 3 clinical signs or inflammation, chronic symptoms of an immune- inflammatory related adverse reaction    Resume LIBTAYO if other immune-mediated demyelinating not described above         adverse reaction improves and remains at Grade 0 to polyradiculoneuropathy,
encephalitis, myasthenia                                  1 after corticosteroid taper to ≤10 mg/day prednisone gravis, neuropathy                                        or equivalent peripheral, myocarditis,
pericarditis, immune thrombocytopenic purpura,
vasculitis, arthralgia,
arthritis, muscular weakness, myalgia,
polymyalgia rheumatica,
Sjogren’s syndrome,
keratitis, stomatitis,
thyroiditis)

– Grade 4 adverse reaction
(excluding endocrinopathies)
– Recurrent severe
Grade 3
– immune-mediated adverse reaction
Persistent Grade 2 or 3
Initial dose of 1 to immune-mediated adverse
2 mg/kg/day prednisone reactions lasting 12 weeks    Permanently discontinue     or equivalent followed or longer (excluding by a taper endocrinopathies)
– Inability to reduce corticosteroid dose to
10 mg or less of prednisone or equivalent per day within 12 weeks
Infusion-related reactionsa
Grade 1 or 2
Interrupt or slow rate of
Initiate symptomatic
Infusion-related reaction                                   infusion management
Grade 3 or 4                  Permanently discontinue
ALT: alanine aminotransferase; AST: aspartate aminotransferase; ULN: upper limit of normal.
a
See also sections 4.4 and 4.8 b
Toxicity should be graded with the current version of National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE).

Special populations

Paediatric population
The safety and efficacy of LIBTAYO in children and adolescents below the age of 18 years have not been established. No data are available.

Elderly
No dose adjustment is recommended for elderly patients. Cemiplimab exposure is similar across all age groups (see sections 5.1 and 5.2). Data are limited in patients ≥75 years on cemiplimab monotherapy.

Renal impairment
No dose adjustment of LIBTAYO is recommended for patients with renal impairment. There are limited data for LIBTAYO in patients with severe renal impairment CLcr 15 to 29 ml/min (see section 5.2).

Hepatic impairment
No dose adjustment is recommended for patients with mild or moderate hepatic impairment. LIBTAYO has not been studied in patients with severe hepatic impairment. There are insufficient data in patients with severe hepatic impairment for dosing recommendations (see section 5.2).

Method of administration

LIBTAYO is for intravenous use. It is administered by intravenous infusion over 30 minutes through an intravenous line containing a sterile, non-pyrogenic, low-protein binding, in-line or add-on filter (0.2 micron to 5 micron pore size).

Other medicinal products should not be co-administered through the same infusion line.

For instructions on dilution of the medicinal product before administration, see section 6.6.