IMDYLLTRA Powder for solution for infusion Ref.[116661] Active ingredients: Tarlatamab

Source: European Medicines Agency (EU)  Revision Year: 2026  Publisher: Amgen Europe B.V., Minervum 7061, 4817 ZK Breda, The Netherlands

4.1. Therapeutic indications

IMDYLLTRA is indicated as monotherapy for the treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC), who require systemic therapy following disease progression on or after first-line treatment with platinum-based chemotherapy.

4.2. Posology and method of administration

IMDYLLTRA treatment should be initiated under the direction of and supervised by physicians experienced in the use of cancer therapy. It should be administered in an appropriate healthcare facility. See table 2 for recommended concomitant medicinal products.

Patients should be monitored from the start of the infusion for 6 to 8 hours on day 1 and day 8. Additional monitoring and monitoring on subsequent infusions is at the discretion of the physician.

On day 1 and day 8, patients should be instructed to remain within proximity of an appropriate healthcare facility for 24 hours starting from each infusion, accompanied by a caregiver.

Both patients and caregivers should be informed on signs and symptoms of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) prior to discharge.

Posology

The recommended dosing schedule of IMDYLLTRA is an initial dose of 1 mg on day 1 followed by 10 mg on days 8, 15, and every 2 weeks thereafter as shown in table 1. Patients should be treated until disease progression or unacceptable toxicity.

Table 1. Recommended dosing schedule of IMDYLLTRA:

Dose of IMDYLLTRA
Day 11 mg
Day 810 mg
Day 15 and every 2 weeks
thereafter
10 mg

Recommended concomitant medicinal products

Concomitant medicinal products for IMDYLLTRA administration should be administered as presented in table 2 to reduce the risk of cytokine release syndrome (see section 4.4).

Table 2. Concomitant medicinal products for day 1 and day 8:

Treatment dayMedicinal productsAdministration
Day 1 and day 8Administer 8 mg of dexamethasone
intravenously (or equivalent)
Within 1 hour prior to IMDYLLTRA
infusion
Intravenous administration of 1 litre
of sodium chloride 9 mg/mL (0.9%)
solution for injection is recommended
per standard of care guidelines
Immediately after completion of
IMDYLLTRA infusion

Restarting IMDYLLTRA after dose delay

If a dose of IMDYLLTRA is delayed, therapy should be restarted based on the recommendations listed in table 3, and the dosing schedule should be resumed accordingly. Recommended concomitant medicinal products should be administered as indicated in table 2.

Table 3. Recommendations for restarting therapy with IMDYLLTRA after dose delay:

Last dose
administered
Time since the last dose
administered
Actiona
1 mg on day 12 weeks or less
(≤14 days)
Administer IMDYLLTRA 10 mg, then resume
with the planned dosing schedule.
Greater than 2 weeks
(>14 days)
Administer IMDYLLTRA 1 mg. If tolerated,
increase to 10 mg 1 week later. Then resume with
the planned dosing schedule.
10 mg on day 83 weeks or less
(≤21 days)
Administer IMDYLLTRA 10 mg, then resume
with the planned dosing schedule.
Greater than 3 weeks
(>21 days)
Administer IMDYLLTRA 1 mg. If tolerated,
increase to 10 mg 1 week later. Then resume with
the planned dosing schedule.
10 mg on day 15
and every 2 weeks
thereafter
4 weeks or less
(≤28 days)
Administer IMDYLLTRA 10 mg, then resume
with the planned dosing schedule.
Greater than 4 weeks
(>28 days)
Administer IMDYLLTRA 1 mg. If tolerated,
increase to 10 mg 1 week later. Then resume with
the planned dosing schedule.

a Administer recommended concomitant medicinal products before and after IMDYLLTRA infusions on day 1 and day 8 and monitor patients accordingly (see table 2).

Dose modifications and management of adverse reactions

No dose reduction for IMDYLLTRA is recommended.

See table 4 for recommended actions for the management of CRS, table 5 for recommended actions for the management of ICANS, and table 6 for the management of other adverse reactions.

Cytokine release syndrome (CRS)

CRS should be diagnosed based on clinical presentation (see section 4.4). Patients should be evaluated and treated for other causes of fever, hypoxia, and hypotension. If CRS is suspected, it should be managed according to the recommendations in table 4. Patients who experience grade 2 or higher CRS (e.g., hypotension not responsive to fluids, or hypoxia requiring supplemental oxygen) should be monitored for CRS signs and symptoms including fever, hypotension and hypoxia using pulse oximetry or cardiac telemetry as indicated. For severe or life-threatening CRS, anti-IL-6 therapy is recommended, for example, tocilizumab and admission in an intensive-care unit (ICU) for supportive therapy.

Table 4. Guidelines for grading, dose modification and management of cytokine release syndromea:

CRS
grade
Defining symptomsIMDYLLTRA
dose modification
Management
Grade 1Symptoms require
symptomatic treatment
only (e.g., fever ≥38°C
without hypotension or
hypoxia).
• Withhold
IMDYLLTRA until
event resolves, then
resume IMDYLLTRA
at the next scheduled
doseb.
• Administer symptomatic
antipyretic treatment
(e.g., paracetamol) for
fever.
• Consider
dexamethasonec (or
equivalent) 4 mg to
10 mg orally or
intravenously.
Grade 2Symptoms require and
respond to moderate
intervention.
• Fever ≥38°C,
• Hypotension
responsive to
fluids not
requiring
vasopressors,
and/or
• Hypoxia
requiring low
flow nasal
cannula or
blow-by.
• Withhold
IMDYLLTRA until
event resolves, then
resume IMDYLLTRA
at the next scheduled
doseb.
• Hospitalisation with
monitoring for fever,
hypotension and hypoxia
using pulse oximetry or,
as indicated, cardiac
telemetry, is
recommended.
• Administer symptomatic
antipyretic treatment
(e.g., paracetamol) for
fever.
• Administer supplemental
oxygen and intravenous
fluids when indicated.
• Consider
dexamethasonec (or
equivalent) 8 mg orally
or intravenously.
• Consider tocilizumab (or
equivalent).

When resuming treatment at
the next planned dose, monitor
patients at the physician's
discretion in an appropriate
healthcare facilityb.
Grade 3Severe symptoms
defined as temperature
≥38°C with:
• Haemodynamic
instability
requiring a
vasopressor (with
or without
vasopressin)
and/or
• Worsening
hypoxia or
respiratory
distress requiring
high flow nasal
canula (>6 L/min
oxygen) or face
mask.
• Withhold
IMDYLLTRA until
the event resolves,
then resume
IMDYLLTRA at the
next scheduled doseb.
• For recurrent grade 3
events, permanently
discontinue
IMDYLLTRA.
In addition to grade 2
treatment:
• Intensive monitoring,
e.g., ICU care is
recommended.
• Administer
dexamethasonec (or
equivalent) 8 mg
intravenously every
8 hours up to 3 doses.
• Vasopressor support as
needed.
• High flow oxygen
support as needed.
• Tocilizumab (or
equivalent) is
recommended.
• Prior to the next dose,
administer concomitant
medicinal products as
recommended for day 1
and day 8 (see table 2).

When resuming treatment at
the next planned dose, monitor
patients at the physician's
discretion in an appropriate
healthcare facilityb.
Grade 4Life-threatening
symptoms defined as
temperature ≥38°C
with:
• Haemodynamic
instability
requiring multiple
vasopressors
(excluding
vasopressin)
and/or
• Worsening
hypoxia or
respiratory
distress despite
oxygen
administration
requiring positive
pressure.
Permanently discontinue
IMDYLLTRA.
• ICU care.
• Per grade 3 treatment.

a CRS based on American Society for Transplantation and Cellular Therapy (ASTCT) Consensus Grading (2019).
b See table 3 for recommendations on restarting IMDYLLTRA after dose delays.
c Taper steroids per standard of care guidelines.
ICU = Intensive Care Unit

Immune effector cell-associated neurotoxicity syndrome (ICANS)

Patients should be monitored for signs and symptoms of ICANS. Other causes of neurologic symptoms should be ruled out. Intensive care should be provided for severe or life-threatening neurologic toxicities. If ICANS is suspected, it should be managed according to the recommendations in table 5.

Table 5. Guidelines for grading, dose modification and management of immune effector cell-associated neurotoxicity syndromea:

ICANS
gradea
Defining
symptoms
IMDYLLTRA dose
modification
Management
Grade 1ICE score 7-9b
with no
depressed level
of consciousness.
• Withhold IMDYLLTRA
until ICANS resolves,
then resume
IMDYLLTRA at the
next scheduled dosec.
• Supportive care.
Grade 2ICE score 3-6b
and/or mild
somnolence
awaking to
voice.
• Withhold IMDYLLTRA
until ICANS resolves,
then resume
IMDYLLTRA at the
next scheduled dosec.
• Supportive care.
• Dexamethasoned (or
equivalent) 8 mg to 10 mg
orally or intravenously.
• If symptoms worsen, repeat
dexamethasone every
12 hours or
methylprednisoloned (or
equivalent) 1 mg/kg
intravenously every
12 hours.
• Monitor neurologic
symptoms and consider
consultation with
neurologist and other
specialists for further
evaluation and management.
• Monitor patients at the
physician's discretion
following the next dose of
IMDYLLTRAc.
Grade 3ICE score 0-2b
and/or depressed
level of
consciousness
awakening only
to tactile
stimulus and/or
any clinical
seizure focal or
generalised that
resolves rapidly

Or

Nonconvulsive
seizures on EEG
that resolve with
intervention
and/or focal or
local oedema
seen on
neuroimaging.
• Withhold IMDYLLTRA
until the ICANS
resolves, then resume
IMDYLLTRA at the
next scheduled dosec.
• If there is no
improvement to
grade ≤1 within 7 days,
permanently discontinue
IMDYLLTRA.
• For recurrent grade 3
events, permanently
discontinue.
• Intensive monitoring, e.g.,
ICU care is recommended.
• Consider mechanical
ventilation for airway
protection. Dexamethasoned
(or equivalent) 10 mg
intravenously every 6 hours
or methylprednisoloned (or
equivalent) 1 mg/kg
intravenously every
12 hours.
• Consider repeat
neuroimaging (CT or MRI)
every 2-3 days if patient has
persistent grade ≥3
neurotoxicity.
• Monitor patients at the
physician's discretion
following the next dose of
IMDYLLTRAc.
Grade 4ICE score 0b
(patient is
unarousable and
unable to
perform ICE)
and/or stupor or
coma and/or
life-threatening
prolonged
seizure
(>5 minutes) or
repetitive clinical
or electrical
seizures without
return to baseline
in between
and/or diffuse
cerebral oedema
on neuroimaging,
decerebrate or
decorticate
posturing or
papilloedema,
cranial nerve VI
palsy, or
Cushing's triad.
• Permanently discontinue
IMDYLLTRA.
• ICU care.
• Consider mechanical
ventilation for airway
protection.
• High-dose corticosteroids
such as methylprednisoloned
1 000 mg/day in divided
doses intravenously for
3 days.
• Consider repeat
neuroimaging (CT or MRI)
every 2-3 days if patient has
persistent grade ≥3
neurotoxicity.
• Treat convulsive status
epilepticus per institutional
guidelines.

a ICANS based on American Society for Transplantation and Cellular Therapy (ASTCT) Consensus Grading (2019).
b If patient is arousable and able to perform Immune Effector Cell-Associated Encephalopathy (ICE) Assessment, assess: Orientation (oriented to year, month, city, hospital = 4 points); Naming (names 3 objects, e.g., point to clock, pen, button = 3 points); Following commands (e.g., "show me 2 fingers" or "close your eyes and stick out your tongue" = 1 point); Writing (ability to write a standard sentence = 1 point); and Attention (count backwards from 100 by ten = 1 point). If patient is unarousable and unable to perform ICE Assessment (grade 4 ICANS) = 0 points.
c See table 3 for recommendations on restarting IMDYLLTRA after dose delays.
d Taper steroids per standard of care guidelines.
CT = Computed Tomography; EEG = Electroencephalogram; ICU = Intensive Care Unit; MRI = Magnetic resonance imaging

Neutropenia and other adverse reactions

Neutropenia and other adverse reactions should be managed in accordance with table 6.

Table 6. Recommended treatment interruptions of IMDYLLTRA for the management of other adverse reactionsa,b:

Adverse
reactions
Severitya Dose modificationb
Neutropenia
(see section 4.4)
Grades 1 and 2No treatment interruption needed.
Grade 3• Interrupt IMDYLLTRA for at
least 3 days and until the event
improves to grade ≤2, then
resume IMDYLLTRA.
Consider using granulocyte-colony
stimulating factor (G-CSF).
Grade 4• Interrupt IMDYLLTRA for at
least 3 days and until the event
improves to grade ≤2, then
resume IMDYLLTRA.
• If event lasts for >7 days or
grade 4 event reoccurs,
permanently discontinue
IMDYLLTRA.
Consider using granulocyte-colony
stimulating factor (G-CSF).
Hepatotoxicity
(see section 4.4)c
Grade 3
Increased ALT or AST or bilirubin
• Withhold IMDYLLTRA until
improved to grade ≤1.
Grade 4
Increased ALT or AST or bilirubin
• Permanently discontinue
IMDYLLTRA.
AST or ALT >3 × ULN with total
bilirubin> 2 × ULN in the absence of
alternative causes
• Permanently discontinue
IMDYLLTRA.
Other adverse
reactions (see
section 4.8)
Grade 3 or 4Withhold IMDYLLTRA until
recovery to grade ≤1 or baseline.

Consider permanently discontinuing
if adverse reaction does not resolve
within 28 days.

• Consider permanent
discontinuation for grade 4
events.

a Severity based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 5.0.
b See table 3 for recommendations on restarting IMDYLLTRA after dose delays.
c For patients with liver enzyme elevations at baseline, multiples of baseline values should be used for hepatotoxicity assessment.
ALT = alanine aminotransferase; AST = aspartate aminotransferase; ULN = upper limit of normal

Special populations

Elderly

No dose adjustment is necessary in elderly patients (≥65 years of age).

Hepatic impairment

No dose adjustment is required in patients with mild hepatic impairment (see section 5.2). Limited data is available in patients with moderate hepatic impairment. IMDYLLTRA has not been studied in patients with severe hepatic impairment. No dose recommendations can be made for patients with moderate or severe hepatic impairment.

Renal impairment

No dose adjustment is required in patients with mild or moderate renal impairment (see section 5.2). IMDYLLTRA has not been studied in patients with severe renal impairment. No dose recommendations can be made for patients with severe renal impairment to end-stage renal disease.

Paediatric population

There is no relevant use of IMDYLLTRA in the paediatric population for the treatment of small cell lung cancer.

Method of administration

IMDYLLTRA is for intravenous use.

IMDYLLTRA is to be reconstituted and then further diluted prior to administration by intravenous infusion.

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

The infusion line for premedication can be used for IMDYLLTRA. An infusion line flush should be conducted between administering concomitant medicinal products and IMDYLLTRA.

Administer the entire contents of IMDYLLTRA as an intravenous infusion over 1 hour at a constant flow rate using an infusion pump, see table 7. The pump should be programmable, lockable, non-elastomeric, and have an alarm.

The infusion line is primed with sodium chloride 9 mg/mL (0.9%) solution for injection OR final prepared IMDYLLTRA.

Upon completion of the IMDYLLTRA infusion, the intravenous infusion line should be flushed over 3-5 minutes using sodium chloride 9 mg/mL (0.9%) solution for injection.

Table 7. Tarlatamab administration information:

Infusion duration for 250 mL
intravenous preparation
Infusion rate (mL/hour)
1 hour250 mL/hour

4.9. Overdose

Doses up to 100 mg every 2 weeks and 200 mg every 3 weeks have been evaluated in clinical trials. In the event of an overdose, the patient must be closely monitored for signs or symptoms of adverse reactions and should be treated symptomatically, and supportive measures instituted as required.

6.3. Shelf life

Unopened vial:

4 years.

Diluted solution for intravenous infusion (infusion bag):

Chemical and physical in-use stability has been demonstrated for 28 days at 2°C to 8°C and 8 hours at 20°C to 25°C.

From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of the user and would normally not be longer than 24 hours at 2°C to 8°C, unless the method of reconstitution and dilution has taken place in controlled and validated aseptic conditions.

6.4. Special precautions for storage

Store and transport refrigerated (2°C to 8°C).

Do not freeze.

Store in the original packaging in order to protect from light.

For storage conditions after reconstitution and dilution of the medicinal product, see section 6.3.

6.5. Nature and contents of container

IMDYLLTRA consists of two packaging configurations. Each IMDYLLTRA pack contains 1 vial of powder for concentrate for solution for infusion and 2 vials of solution (stabiliser).

IMDYLLTRA 1 mg powder for concentrate and solution for solution for infusion:

  • 1 mg tarlatamab powder in a Type 1 glass vial with an elastomeric stopper, aluminium seal and a grey flip-off cap
  • 7 mL solution in a Type 1 glass vial with an elastomeric stopper, aluminium seal and a white flip-off cap

IMDYLLTRA 10 mg powder for concentrate and solution for solution for infusion:

  • 10 mg tarlatamab powder in a Type 1 glass vial with an elastomeric stopper, aluminium seal and an orange flip-off cap
  • 7 mL solution in a Type 1 glass vial with an elastomeric stopper, aluminium seal and a white flip-off cap

6.6. Special precautions for disposal and other handling

Aseptic preparation

Strictly observe aseptic technique when preparing the solution for infusion since tarlatamab vials do not contain antimicrobial preservatives.

Other instructions

  • Reconstitution of IMDYLLTRA is with water for injections. Do not use the solution (stabiliser) to reconstitute IMDYLLTRA. The solution (stabiliser) is used to coat the infusion bag prior to addition of reconstituted IMDYLLTRA to prevent adsorption of IMDYLLTRA to infusion bags and infusion line.
  • Infusion bags composed of ethyl vinyl acetate (EVA), polyolefin, and polyvinyl chloride (PVC) have been shown to be compatible with tarlatamab at the specified administration conditions.
  • Infusion line and catheter materials composed of polyolefin, PVC, and polyurethane have been shown to be compatible with tarlatamab at the specified administration conditions.
  • The use of Closed System Transfer Device (CSTD) is not recommended due to potential risk for medication error. Compatibility testing of vial adaptor CSTDs with IMDYLLTRA has not been performed.

Preparation of the solution for infusion

Reconstitution of tarlatamab

Table 10. Required amount of water for injections to reconstitute IMDYLLTRAa:

IMDYLLTRA vial strengthAmount of water for
injections needed to
reconstitute IMDYLLTRA
Final concentration
1 mg1.3 mL0.9 mg/mL
10 mg4.4 mL2.4 mg/mL

1. Transfer required amount of water for injections (refer to table 10) into the tarlatamab vial to provide a final tarlatamab concentration of 0.9 mg/mL (1 mg vial) or 2.4 mg/mL (10 mg vial). Direct the water along the walls of the IMDYLLTRA vial and not directly on the lyophilised powder.

  • Do not use the solution (stabiliser) to reconstitute IMDYLLTRA.

2. Gently swirl contents. Do not shake.

3. Visually inspect that the solution is clear to slightly opalescent, colourless to slightly yellow. Do not use if solution is cloudy or has particulates.

Preparation of IMDYLLTRA infusion bag

Table 11. Preparation guide for 1-hour infusion:

IMDYLLTRA
vial strength
IMDYLLTRA
dose
Volume of sodium
chloride 9 mg/mL
(0.9%) solution for
injection to
withdraw from
infusion bag
Volume of
solution
(stabiliser) to
add to infusion
bag
Volume of
reconstituted
IMDYLLTRA to
add to infusion
bag
1 mg1 mg14 mL13 mL1.1 mL
10 mg10 mg17 mL13 mL4.2 mL

Note: the final concentrations for the different strength vials are NOT the same following reconstitution.

1. Use an infusion bag pre-filled with 250 mL sodium chloride 9 mg/mL (0.9%) solution for injection.

2. Withdraw the required volume of sodium chloride 9 mg/mL (0.9%) solution for injection from the pre-filled infusion bag and discard (refer to table 11). Disregard any overfill in the infusion bag.

3. Add solution (stabiliser).

  • To coat the infusion bag, transfer 13 mL of the solution (stabiliser) to the infusion bag containing sodium chloride 9 mg/mL (0.9%) solution for injection.
  • Gently mix the contents of the bag to avoid foaming. Do not shake.

4. Add reconstituted IMDYLLTRA.

  • Transfer the required volume of reconstituted IMDYLLTRA into the stabilised infusion bag containing sodium chloride 9 mg/mL (0.9%) solution for injection and the solution (stabiliser). Refer to table 11.
  • Gently mix the contents of the bag to avoid foaming. Do not shake.

5. Remove the air from the infusion bag using an empty syringe to avoid foaming.

6. Prime infusion line with sodium chloride 9 mg/mL (0.9%) solution for injection or final prepared product from the infusion bag.

The storage time per section 6.3 includes total time permitted from point of reconstitution of first vial to the end of administration. After removal from refrigeration, allow the infusion bag to reach room temperature and complete administration of the diluted IMDYLLTRA infusion solution within the allowable room temperature storage time (including infusion time). If the prepared tarlatamab infusion bag is not administered within the time frames and temperatures indicated, it must be discarded; it should not be refrigerated again.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

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