DATROWAY Powder for concentrate for solution for infusion Ref.[115207] Active ingredients: Datopotamab deruxtecan

Source: European Medicines Agency (EU)  Revision Year: 2025  Publisher: Daiichi Sankyo Europe GmbH, Zielstattstrasse 48, 81379 Munich, Germany

4.1. Therapeutic indications

Breast cancer

Datroway as monotherapy is indicated for the treatment of adult patients with unresectable or metastatic hormone receptor (HR)-positive, HER2-negative breast cancer who have received endocrine therapy and at least one line of chemotherapy in the advanced setting (see section 5.1).

4.2. Posology and method of administration

Datroway should be prescribed by a physician and administered under the supervision of a healthcare professional experienced in the use of anticancer medicinal products.

Patient selection

Patients for treatment of unresectable or metastatic HR-positive, HER2-negative breast cancer should be selected on the basis of a documented HER2-negative result assessed by a CE marked IVD if available, or an alternative validated test.

Posology

The recommended dose of Datroway is 6 mg/kg (up to a maximum of 540 mg for patients ≥90 kg) of body weight given as an intravenous infusion once every 3 weeks (21-day cycle) until disease progression or unacceptable toxicity.

Premedication and prophylactic medicinal products

Prior to each infusion of Datroway, a premedication regimen for the prevention of infusion-related reactions that consists of an antihistamine and paracetamol (with or without glucocorticoids) should be considered (see section 4.8).

It is also recommended that patients receive prophylactic antiemetic agents (dexamethasone with 5-HT3 antagonists as well as other medicinal products, such as NK1 receptor antagonists) prior to infusion of Datroway and on subsequent days as needed.

For prophylactic treatment for keratitis and stomatitis, see section 4.4.

Dose modifications

Dose modifications for infusion-related reactions

The infusion rate of Datroway should be slowed or interrupted if the patient develops an infusion-related reaction. Datroway should be permanently discontinued in case of life-threatening infusion-related reactions.

Dose modifications for adverse reactions

Management of adverse reactions may require dose delay, dose reduction, or treatment discontinuation per guidelines provided in Tables 1 and 2.

Datroway dose should not be re-escalated after a dose reduction is made.

Table 1. Dose reductions for adverse reactions:

Recommended starting dose6 mg/kg (up to a maximum of 540 mg for patients ≥90 kg)
First dose reduction4 mg/kg (up to a maximum of 360 mg for patients ≥90 kg)
Second dose reduction3 mg/kg (up to a maximum of 270 mg for patients ≥90 kg)

Table 2. Dose modifications for adverse reactions:

Adverse reactionSeverity*Dose modification
Interstitial lung disease
(ILD)/pneumonitis [see
sections 4.4 and 4.8]
Asymptomatic
ILD/pneumonitis (Grade 1)
Delay dose until resolved to
Grade 0#, then:
• if resolved in 28 days or less
from date of onset, maintain
dose.
• if resolved in greater than
28 days from date of onset,
reduce dose one level (see
Table 1).
• consider corticosteroid
treatment as soon as
ILD/pneumonitis is
suspected.
Symptomatic
ILD/pneumonitis (Grade 2 or
greater)
• Permanently discontinue.
• Promptly initiate
corticosteroid treatment as
soon as ILD/pneumonitis is
suspected.
Keratitis [see sections 4.4 and
4.8]
Grade 2• Delay dose until resolved to
Grade 1 or less, then
maintain dose.
Grade 3• Delay dose until resolved to
Grade 1 or less, then reduce
the dose by 1 level (see
Table 1).
Grade 4• Permanently discontinue.
Stomatitis [see sections 4.4 and
4.8]
Grade 2• Delay dose until resolved to
Grade 1 or less.
• Restart at the same dose for
first occurrence.
• Consider restarting at
reduced dose level (see
Table 1) if recurrent.
Grade 3• Delay dose until resolved to
Grade 1 or less.
• Restart at reduced dose level
(see Table 1).
Grade 4• Permanently discontinue.

* Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0.
# Grade 0 refers to full resolution of ILD/pneumonitis, including the disappearance of radiological findings associated with active ILD/pneumonitis. Residual scarring or fibrosis following recovery of ILD/pneumonitis is not considered to be active disease.

Delayed or missed dose

If a planned dose is delayed or missed, it should be administered as soon as possible without waiting until the next planned cycle. The schedule of administration should be adjusted to maintain a 3-week interval between doses.

Special populations

Elderly

No dose adjustment of Datroway is required in patients aged 65 years or older. Data from datopotamab deruxtecan in patients aged 85 years or older are limited.

Renal impairment

No dose adjustment is required in patients with mild to moderate (creatinine clearance [CLcr] ≥30 and <90 mL/min) renal impairment (see section 5.2). The recommended dosage of Datroway has not been established in patients with severe renal impairment (see section 5.2). Patients with severe renal impairment should be monitored carefully. In patients with moderate renal impairment at baseline who received datopotamab deruxtecan 6 mg/kg, a higher incidence of serious adverse reactions was observed compared to those with normal renal function.

Hepatic impairment

No dose adjustment is required in patients with mild (total bilirubin ≤ upper limit of normal (ULN) and any aspartate aminotransferase (AST) > ULN or total bilirubin >1 to 1.5 times ULN and any AST) hepatic impairment. There are limited data to make a recommendation on dose adjustment in patients with moderate (total bilirubin >1.5 to 3 times ULN and any AST) hepatic impairment. Insufficient data are available in patients with severe (total bilirubin >3 times ULN and any AST) hepatic impairment. Therefore, patients with moderate and severe hepatic impairment should be monitored carefully (see section 4.4 and 5.2).

Paediatric population

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

Method of administration

Datroway is for intravenous use. It must be reconstituted and diluted by a healthcare professional and administered as an intravenous infusion. Datroway must not be administered as an intravenous push or bolus.

The first infusion is to be administered over 90 minutes. Patients should be observed during the infusion and for at least 30 minutes following the initial dose for signs or symptoms of infusion-related reactions.

Subsequent infusions are to be administered over 30 minutes if prior infusions were tolerated. Patients should be observed during the infusion and for at least 30 minutes after infusion.

Precautions to be taken before handling or administering the medicinal product

This medicinal product contains a cytotoxic component, which is covalently attached to the monoclonal antibody (see special handling and disposal procedures in section 6.6).

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

4.9. Overdose

There is currently no specific treatment in the event of an overdose. Higher than the indicated dosing may increase risk of adverse reactions. Physicians should follow general supportive measures and institute appropriate treatment.

6.3. Shelf life

Unopened vial:

3 years.

Reconstituted solution:

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

Diluted solution:

It is recommended that the diluted solution be used immediately. If not used immediately, the diluted solution may be stored at room temperature (≤25°C) for up to 4 hours or in a refrigerator at 2°C to 8°C for up to 24 hours, protected from light.

The maximum time from reconstitution of the vial through the end of administration should not exceed 24 hours. Discard if storage time exceeds these limits.

6.4. Special precautions for storage

Store in a refrigerator (2°C–8°C).

Do not freeze.

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

6.5. Nature and contents of container

Datroway is provided in a 10 mL Type 1 amber borosilicate glass vial sealed with a fluoro-resin laminated butyl rubber stopper, and a polypropylene/aluminium blue flip-off crimp cap.

Each carton contains 1 vial.

6.6. Special precautions for disposal and other handling

Datroway contains a cytotoxic component and should be administered under the supervision of a physician experienced in the use of cytotoxic agents. Appropriate procedures for proper preparation, handling and disposal of antineoplastic and cytotoxic medicinal products should be used.

Appropriate aseptic technique should be used for the following reconstitution and dilution procedures.

Reconstitution:

  • Reconstitute immediately before dilution.
  • More than one vial may be needed for a full dose. Calculate the dose (mg), the total volume of reconstituted Datroway solution required, and the number of vial(s) of Datroway needed (see section 4.2).
  • Reconstitute each 100 mg vial using a sterile syringe to slowly inject 5 mL of water for injection into each vial to obtain a final concentration of 20 mg/mL.
  • Swirl the vial gently until completely dissolved. Do not shake.
  • If not used immediately, store the reconstituted Datroway vials in a refrigerator at 2°C to 8°C for up to 24 hours, protected from light. Do not freeze.
  • The reconstituted product contains no preservative and is intended for single use only. Discard unused reconstituted Datroway after 24 hours refrigerated.

Dilution:

  • Withdraw the calculated amount from the vial(s) using a sterile syringe. Inspect the reconstituted solution for particulates and discolouration. The solution should be clear and colourless to light yellow. Do not use if visible particles are observed or if the solution is cloudy or discoloured.
  • Dilute the calculated volume of reconstituted Datroway in an infusion bag containing 100 mL of 5% glucose solution. Do not use sodium chloride solution (see section 6.2). An infusion bag made of polyvinylchloride (PVC) or polyolefin (polypropylene (PP) or copolymer of ethylene and propylene) is recommended.
  • Gently invert the infusion bag to thoroughly mix the solution. Do not shake.
  • Cover the infusion bag to protect from light.
  • If not used immediately, store at room temperature (≤25°C) for up to 4 hours including preparation and infusion, or in a refrigerator at 2°C to 8°C for up to 24 hours, protected from light. Do not freeze.
  • Discard any unused portion left in the vial.

Administration:

  • The maximum time from reconstitution of the vial through the end of administration should not exceed 24 hours. Discard if storage time exceeds these limits.
  • If the prepared infusion solution was stored refrigerated (2°C to 8°C), it is recommended that the solution be allowed to reach to room temperature prior to administration, protected from light.
  • Administer Datroway as an intravenous infusion only with an infusion line and tubing set made of PVC, polybutadiene (PBD), or low density polyethylene (LDPE).
  • Administer Datroway with a 0.2 micron in-line polytetrafluoroethylene (PTFE), polyethersulfone (PES) or nylon 66 filter.
  • Do not administer as an intravenous push or bolus (see section 4.2).
  • Cover the infusion bag to protect from light.
  • Do not mix Datroway with other medicinal products or administer other medicinal products through the same intravenous line.

Disposal:

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

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