Fertility warning
This medicine may affect fertility.
Leaflet DATROWAY 100mg powder for concentrate for solution for infusion
- Product code:
- W72143001
- Quantity:
- 1
- Indicated for:
- unresectable or metastatic HR-positive, HER2-negative breast cancer after endocrine therapy and at least one chemotherap
- Route of administration:
- infusion
- Substance:
- datopotamab deruxtecan (TROP2-directed antibody-drug conjugate with a topoisomerase I inhibitor)
- ATC
- L01FX35 — Antineoplastic and immunomodulating agents | Monoclonal antibodies and antibody drug conjugates | Other monoclonal antibodies and antibody drug conjugates
Datopotamab deruxtecan combines an anti-TROP2 antibody with a cell-killing medicine delivered into tumour cells. It treats adults with inoperable or metastatic HR-positive, HER2-negative breast cancer after endocrine therapy and chemotherapy. In the USA, it is also approved for selected patients with triple-negative breast cancer or EGFR-mutated lung cancer.
It is given by intravenous infusion, usually every 3 weeks, in an oncology centre. The dose depends on weight and tolerability. The team recommends anti-sickness medicines, a steroid mouthwash and preservative-free lubricating eye drops. Attend eye examinations and do not wear contact lenses without the specialist's agreement.
Side effects include painful mouth ulcers, nausea, vomiting, tiredness, hair loss, constipation and dry eyes. Corneal inflammation, changes in blood tests and infusion reactions may occur. The medicine can cause severe, sometimes fatal non-infectious lung inflammation.
Tell the oncology team immediately about a new cough, breathlessness, fever, eye pain, altered vision or mouth sores that prevent eating. The doctor may delay a dose, reduce it or stop treatment. Avoid pregnancy and breastfeeding; continue contraception after the last dose for the recommended period. This medicine is not interchangeable with trastuzumab deruxtecan.
It is given by intravenous infusion, usually every 3 weeks, in an oncology centre. The dose depends on weight and tolerability. The team recommends anti-sickness medicines, a steroid mouthwash and preservative-free lubricating eye drops. Attend eye examinations and do not wear contact lenses without the specialist's agreement.
Side effects include painful mouth ulcers, nausea, vomiting, tiredness, hair loss, constipation and dry eyes. Corneal inflammation, changes in blood tests and infusion reactions may occur. The medicine can cause severe, sometimes fatal non-infectious lung inflammation.
Tell the oncology team immediately about a new cough, breathlessness, fever, eye pain, altered vision or mouth sores that prevent eating. The doctor may delay a dose, reduce it or stop treatment. Avoid pregnancy and breastfeeding; continue contraception after the last dose for the recommended period. This medicine is not interchangeable with trastuzumab deruxtecan.
General data about DATROWAY 100mg
- Substance:
- datopotamab deruxtecan
- Date of latest medicines list:
- 01-09-2026
- Product code:
- W72143001
- Concentration:
- 100mg
- Pharmaceutical form:
- powder for concentrate for solution for infusion
- Quantity:
- 1
- Product type:
- Original
- Prescription status:
- P-RF — Medicines dispensed with a medical prescription that is retained by the pharmacy and cannot be renewed.
Official documents
- Added to database:
- 13/05/2025
- Source record updated:
- 09/02/2026
Precautions:
Driving impairment
This medicine may affect your ability to drive or use machines.
Anaphylaxis
Risk of severe allergic reaction. Seek urgent medical help if serious symptoms occur.
General warning
Read the package leaflet before use.
Cytotoxic / special handling
Handle with special care.
Contraception required
Effective contraception is required during treatment.
Contraindicated during breastfeeding
Do not use this medicine while breastfeeding.
Additional monitoring
This medicine is subject to additional monitoring.
Pregnancy warning
Use during pregnancy only on medical advice.
Pediatric warning
Use in children only as recommended in the leaflet or by a doctor.
Teratogenic / fetal risk
This medicine may affect fetal development.
Vision disturbances
This medicine may cause vision disturbances.
Contents of the package leaflet for the medicine DATROWAY 100mg powder for concentrate for solution for infusion
Find in leaflet
Leaflet DATROWAY 100mg
1. NAME OF THE MEDICINAL PRODUCT
Datroway 100 mg powder for concentrate for solution for infusion
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
One vial of powder for concentrate for solution for infusion contains 100 mg of datopotamabderuxtecan. After reconstitution, one vial of 5 mL solution contains 20 mg/mL of datopotamabderuxtecan (see section 6.6).
Datopotamab deruxtecan is an antibody-drug conjugate (ADC) that contains a humanised anti-TROP2
IgG1 monoclonal antibody (mAb) produced by mammalian (Chinese Hamster Ovary) cells, covalentlylinked to DXd, an exatecan derivative and a topoisomerase I inhibitor, via a tetrapeptide-basedcleavable linker. Approximately 4 molecules of deruxtecan are attached to each antibody molecule.
Excipient with known effectEach 100 mg vial contains 1.50 mg of polysorbate 80 (E 433).
For the full list of excipients, see section 6.1.
3. PHARMACEUTICAL FORM
Powder for concentrate for solution for infusion.
White to yellowish white lyophilised powder, which has a cake-like appearance.
4. CLINICAL PARTICULARS
4.1 Therapeutic indications
Breast cancer
Datroway as monotherapy is indicated for the treatment of adult patients with unresectable ormetastatic hormone receptor (HR)-positive, HER2-negative breast cancer who have receivedendocrine 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 healthcareprofessional experienced in the use of anticancer medicinal products.
Patient selection
Patients for treatment of unresectable or metastatic HR-positive, HER2-negative breast cancer shouldbe selected on the basis of a documented HER2-negative result assessed by a CE marked IVD ifavailable, or an alternative validated test.
PosologyThe recommended dose of Datroway is 6 mg/kg (up to a maximum of 540 mg for patients ≥90 kg) ofbody weight given as an intravenous infusion once every 3 weeks (21-day cycle) until diseaseprogression or unacceptable toxicity.
Premedication and prophylactic medicinal products
Prior to each infusion of Datroway, a premedication regimen for the prevention of infusion-relatedreactions that consists of an antihistamine and paracetamol (with or without glucocorticoids) should beconsidered (see section 4.8).
It is also recommended that patients receive prophylactic antiemetic agents (dexamethasone with5-HT3 antagonists as well as other medicinal products, such as NK1 receptor antagonists) prior toinfusion of Datroway and on subsequent days as needed.
For prophylactic treatment for keratitis and stomatitis, see section 4.4.
Dose modificationsDose modifications for infusion-related reactions
The infusion rate of Datroway should be slowed or interrupted if the patient develops aninfusion-related reaction. Datroway should be permanently discontinued in case of life-threateninginfusion-related reactions.
Dose modifications for adverse reactions
Management of adverse reactions may require dose delay, dose reduction, or treatment discontinuationper 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 dose 6 mg/kg (up to a maximum of 540 mg for patients ≥90 kg)
First dose reduction 4 mg/kg (up to a maximum of 360 mg for patients ≥90 kg)
Second dose reduction 3 mg/kg (up to a maximum of 270 mg for patients ≥90 kg)
Table 2: Dose modifications for adverse reactions
Adverse reaction Severity* Dose modification
Interstitial lung disease Asymptomatic Delay dose until resolved to(ILD)/pneumonitis [see ILD/pneumonitis (Grade 1) Grade 0#, then:sections 4.4 and 4.8] * if resolved in 28 days or lessfrom date of onset, maintaindose.
* if resolved in greater than28 days from date of onset,reduce dose one level (see
Table 1).
* consider corticosteroidtreatment as soon as
ILD/pneumonitis issuspected.
Symptomatic * Permanently discontinue.
ILD/pneumonitis (Grade 2 or * Promptly initiategreater) corticosteroid treatment assoon as ILD/pneumonitis issuspected.
Adverse reaction Severity* Dose modification
Keratitis [see sections 4.4 and Grade 2 * Delay dose until resolved to4.8] Grade 1 or less, thenmaintain dose.
Grade 3 * Delay dose until resolved to
Grade 1 or less, then reducethe dose by 1 level (see
Table 1).
Grade 4 * Permanently discontinue.
Stomatitis [see sections 4.4 and Grade 2 * Delay dose until resolved to4.8] Grade 1 or less.
* Restart at the same dose forfirst occurrence.
* Consider restarting atreduced 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 findingsassociated with active ILD/pneumonitis. Residual scarring or fibrosis following recovery of ILD/pneumonitisis not considered to be active disease.
Delayed or missed doseIf a planned dose is delayed or missed, it should be administered as soon as possible without waitinguntil the next planned cycle. The schedule of administration should be adjusted to maintain a 3-weekinterval between doses.
Special populationsElderly
No dose adjustment of Datroway is required in patients aged 65 years or older. Data fromdatopotamab deruxtecan in patients aged 85 years or older are limited.
Renal impairmentNo 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 beenestablished in patients with severe renal impairment (see section 5.2). Patients with severe renalimpairment should be monitored carefully. In patients with moderate renal impairment at baseline whoreceived datopotamab deruxtecan 6 mg/kg, a higher incidence of serious adverse reactions wasobserved compared to those with normal renal function.
Hepatic impairmentNo 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 inpatients 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 bemonitored carefully (see section 4.4 and 5.2).
Paediatric populationThe safety and efficacy in children and adolescents below 18 years of age have not been established.
No data are available.
Method of administrationDatroway is for intravenous use. It must be reconstituted and diluted by a healthcare professional andadministered as an intravenous infusion. Datroway must not be administered as an intravenous push orbolus.
The first infusion is to be administered over 90 minutes. Patients should be observed during theinfusion and for at least 30 minutes following the initial dose for signs or symptoms of infusion-relatedreactions.
Subsequent infusions are to be administered over 30 minutes if prior infusions were tolerated. Patientsshould be observed during the infusion and for at least 30 minutes after infusion.
Precautions to be taken before handling or administering the medicinal productThis medicinal product contains a cytotoxic component, which is covalently attached to themonoclonal antibody (see special handling and disposal procedures in section 6.6).
For instructions on reconstitution and dilution of the medicinal product before administration, seesection 6.6.
4.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
4.4 Special warnings and precautions for use
Traceability
In order to improve the traceability of biological medicinal products, the name and the batch numberof the administered product should be clearly recorded.
Interstitial lung disease/pneumonitis
Cases of interstitial lung disease (ILD), including pneumonitis, have been reported in patients treatedwith Datroway (see section 4.8). Fatal outcomes have been observed.
Patients should be advised to immediately report cough, dyspnoea, fever, and/or any new or worseningrespiratory symptoms. Patients should be monitored for signs and symptoms of ILD/pneumonitis.
Evidence of ILD/pneumonitis should be promptly investigated. Patients with suspected
ILD/pneumonitis should be evaluated by radiographic imaging. Consultation with a pulmonologistshould be considered. For asymptomatic (Grade 1) ILD/pneumonitis, consider corticosteroid treatment(e.g. ≥ 0.5 mg/kg/day prednisolone or equivalent). Datroway should be delayed until recovery to
Grade 0 and may be resumed according to instructions in Table 2 (see section 4.2). For symptomatic
ILD/pneumonitis (Grade 2 or greater), promptly initiate systemic corticosteroid treatment(e.g. ≥ 1 mg/kg/day prednisolone or equivalent) and continue for at least 14 days followed by gradualtaper for at least 4 weeks. Datroway should be permanently discontinued in patients who arediagnosed with symptomatic (Grade 2 or greater) ILD/pneumonitis (see section 4.2). Patients with ahistory of ILD/pneumonitis may be at increased risk of developing ILD/pneumonitis and should bemonitored carefully.
HypersensitivitySerious, anaphylactic reactions have been observed with datopotamab deruxtecan. Patients should beobserved closely for hypersensitivity/allergic reactions, which may have the same clinical presentationas an infusion-related reaction. Medicinal products to treat such reactions, as well as emergencyequipment, should be available for immediate use. In the event of a serious hypersensitivity reaction,datopotamab deruxtecan treatment must be immediately and permanently discontinued.
Keratitis
Datroway can cause ocular surface undesirable effects including keratitis. Signs and symptoms ofkeratitis may include dry eye, increased lacrimation, photophobia, and detrimental changes to vision(see section 4.8).
Patients should be advised to use preservative-free lubricant eye drops several times daily forprophylaxis. Patients should be advised to avoid use of contact lenses unless directed by an eye careprofessional. Patients should be promptly referred for appropriate ophthalmologic assessments for anynew or worsening ocular signs and symptoms that could suggest keratitis. Keratitis should bemonitored and if diagnosis is confirmed, Datroway should be dose delayed, dose reduced, orpermanently discontinued (see section 4.2).
Patients with clinically significant corneal disease were excluded from the study (see section 5.1).
Patients with pre-existing keratitis should be carefully monitored.
Stomatitis
Stomatitis, including mouth ulcers and oral mucositis, have been reported in patients being treatedwith Datroway (see section 4.8).
In addition to practicing good oral hygiene, when starting Datroway and throughout treatment, dailyuse of a steroid-containing mouthwash (e.g. dexamethasone oral solution 0.1 mg/mL 4 times daily or asimilar steroid-containing mouthwash regimen) is recommended for prophylaxis and treatment. Whereclinically indicated, antifungal agents may be considered in accordance with local guidelines. In theabsence of a prophylactic steroid-containing mouthwash, use of bland mouth rinses (e.g. a non-alcoholic and/or bicarbonate-containing mouthwash) per local guidelines is recommended. Ice chips orice water held in the mouth throughout the infusion may also be considered. If stomatitis does occur,frequency of mouthwashes may be increased and/or other topical treatments may be used. Based onthe severity of the adverse reaction, dose delay, dose reduce, or permanently discontinue Datroway(see section 4.2).
Embryo-foetal toxicity
Based on findings in animals and its mechanism of action, the topoisomerase I inhibitor component of
Datroway can cause embryo-foetal harm when administered to a pregnant woman.
The pregnancy status of females of childbearing potential should be verified prior to the initiation of
Datroway. The patient should be informed of the potential risks to the foetus. Females of reproductivepotential should be advised to use effective contraception during treatment and for at least 7 monthsfollowing the last dose of Datroway. Male patients with female partners of reproductive potentialshould be advised to use effective contraception during treatment with Datroway and for at least4 months after the last dose of Datroway (see section 4.6).
Patients with moderate or severe hepatic impairment
There are limited data in patients with moderate hepatic impairment and severe hepatic impairment.
As metabolism and biliary excretion are the primary routes of elimination of the topoisomerase Iinhibitor, DXd, Datroway should be administered with caution in patients with moderate and severehepatic impairment (see sections 4.2 and 5.2).
Excipient with known effectThis medicine contains 1.5 mg of polysorbate 80 in each vial. Polysorbates may cause allergicreactions.
4.5 Interaction with other medicinal products and other forms of interaction
No clinical drug interaction studies with datopotamab deruxtecan have been conducted. However,clinical drug-drug interaction studies were conducted with trastuzumab deruxtecan (T-DXd), whichcontains the same DXd payload as Datroway. The Cmax of DXd was not affected by ritonavir (inhibitorof CYP3A4 and OATP1B1 and 1B3) or itraconazole (inhibitor of CYP3A4). The AUC was increased1.2-fold by both inhibitors which was not considered clinically relevant. Therefore, inhibitors of
CYP3A4, OATP1B1 and OATP1B3 will most likely not have a clinically relevant effect on the PK ofderuxtecan released from datopotamab deruxtecan.
4.6 Fertility, pregnancy and lactation
Women of childbearing potential/Contraception in females and males
The pregnancy status of women of childbearing potential should be verified prior to initiation of
Datroway.
Women of childbearing potential should use effective contraception during treatment with Datrowayand for at least 7 months following the last dose.
Men with female partners of childbearing potential should use effective contraception during treatmentwith Datroway and for at least 4 months following the last dose.
PregnancyThere are no available data on the use of Datroway in pregnant women. However, based on findings inanimals and its mechanism of action, the topoisomerase I inhibitor component, DXd, can be expectedto cause embryo-foetal harm when administered to pregnant women (see section 5.3).
Datroway is not recommended during pregnancy and in women of childbearing potential not usingcontraception. Patients should be informed of the potential risks to the foetus before they becomepregnant and to contact their doctor immediately if they become pregnant.
Breast-feedingIt is not known if datopotamab deruxtecan is excreted in human milk. Human IgG is excreted inhuman milk. Because of the potential for serious adverse reactions in breast-fed children, womenshould discontinue breast-feeding prior to initiating treatment with Datroway. Women may beginbreast-feeding 1 month after concluding treatment.
FertilityNo human data on the effect of datopotamab deruxtecan on fertility are available. Based on resultsfrom animal toxicity studies, Datroway may impair male and female reproductive function and fertility(see section 5.3).
Both men and women should seek advice on fertility preservation before treatment. It is not knownwhether datopotamab deruxtecan or its metabolites are found in seminal fluid. Male patients must notfreeze or donate sperm throughout the treatment period, and for at least 4 months after the final doseof Datroway. Females must not donate, or retrieve for their own use, ova throughout the treatmentperiod and for at least 7 months after the final dose of Datroway.
4.7 Effects on ability to drive and use machines
Datroway may influence the ability to drive and use machines. Patients should be advised to usecaution when driving or operating machines in case they experience fatigue or vision changes duringtreatment with Datroway (see section 4.8).
4.8 Undesirable effects
Summary of safety profile
The pooled safety profile has been assessed from two clinical studies involving 443 patients whoreceived Datroway 6 mg/kg body weight for the treatment of breast cancer. The median exposure to
Datroway in this data set was 6.2 months (range 0.7 to 28.5 months).
The most common adverse reactions were stomatitis (64.8%), nausea (57.6%), fatigue (42.7%),alopecia (37.2%), constipation (33.0%), vomiting (26.0%), dry eye (25.5%), COVID-19 (17.8%),keratitis (17.8%), anaemia (17.2%), decreased appetite (16.3%), AST increased (16.0%), rash(15.3%), diarrhoea (12.9%), neutropenia (12.0%) and alanine aminotransferase (ALT) increased(10.4%).
The most common Grade 3/4 adverse reactions were stomatitis (7.9%), fatigue (4.3%), anaemia(3.2%), AST increased (2.7%), vomiting (1.6%), ALT increased (1.6%), nausea (1.4%), urinary tractinfection (1.4%), COVID-19 (1.1%), decreased appetite (1.1%), neutropenia (1.1%) and pneumonia(1.1%). Grade 5 adverse reactions occurred in 0.7% of patients and were due to ILD/pneumonitis,dyspnoea and sepsis.
The most common serious adverse reactions were COVID-19 (1.4%), urinary tract infection (1.1%),
ILD/pneumonitis (1.1%) and sepsis (1.1%).
The frequency of treatment discontinuation due to adverse reactions was 3.6%. The most commonadverse reaction leading to treatment discontinuation was ILD/pneumonitis (2.0%). The frequency ofdose reductions due to adverse reactions was 21.0%. The most common adverse reactions leading todose reduction were stomatitis (12.9%), fatigue (3.2%), nausea (1.8%) and keratitis (1.4%). Thefrequency of dose interruptions due to adverse reactions was 19.6%. The most common adversereactions leading to dose interruption were stomatitis (5.2%), COVID-19 (4.1%), fatigue (2.3%),
ILD/pneumonitis (1.6%), pneumonia (1.6%), keratitis (1.4%) and infusion-related reaction (1.1%).
Tabulated list of adverse reactionsTable 3 presents adverse reactions reported with Datroway. Adverse reactions are listed by System
Organ Class and frequency category. The adverse reaction frequencies are based on all-cause adverseevent frequencies, where a proportion of the events for an adverse reaction may have other causes thandatopotamab deruxtecan, such as the disease, other medicinal products or unrelated causes. Theseverity of adverse drug reactions was assessed based on the Common Terminology Criteria for
Adverse Events (CTCAE), defining Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe,
Grade 4 = life threatening, and Grade 5 = death.
Frequency categories are defined as: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon(≥ 1/1 000 to < 1/100), rare (≥ 1/10 000 to < 1/1 000), very rare (< 1/10 000), and not known (cannotbe estimated from the available data). Within each frequency grouping, adverse reactions are presentedin the order of decreasing seriousness.
Table 3: Adverse reactions in patients treated with datopotamab deruxtecan 6 mg/kg
System organ class Frequency category Adverse reactions
Infections and infestationsVery common COVID-19a
Common urinary tract infection,pneumoniab, sepsis
Blood and lymphatic system disordersVery common anaemia, neutropeniac
Common leukopenia
Immune system disordersNot known anaphylactic reaction
Metabolism and nutrition disordersVery common decreased appetite
Nervous system disordersCommon dysgeusia
Eye disordersVery common keratitisd, dry eye
Common conjunctivitise, blurred vision,lacrimation increased, blepharitis,meibomian gland dysfunction,photophobia
Uncommon visual impairment
Respiratory, thoracic and mediastinal disordersCommon ILD/pneumonitisf, dyspnoea
Gastrointestinal disordersVery common stomatitisg, vomiting, nausea,diarrhoea, constipation
Common dry mouth
Skin and subcutaneous tissue disordersVery common alopecia, rashh
Common pruritus, dry skin, skinhyperpigmentationi, madarosis
General disorders and administration site conditionsVery common fatiguej
InvestigationsVery common aspartate aminotransferaseincreased, alanineaminotransferase increased
Injury, poisoning and procedural complicationsCommon infusion-related reactionka Including COVID-19, COVID-19 pneumonia, SARS-CoV-2 test positive.b Including pneumonia, lower respiratory tract infection and lower respiratory tract infection fungal.c Including neutropenia and neutrophil count decreased.d Including keratitis, punctate keratitis and ulcerative keratitis.e Including conjunctivitis, conjunctival disorder, conjunctival hyperaemia and conjunctival irritation.f Including interstitial lung disease and pneumonitis.g Including stomatitis, aphthous ulcer, glossitis, mouth ulceration, odynophagia, oral pain, oropharyngeal painand pharyngeal inflammation.h Including rash, erythematous rash, maculo-papular rash and pruritic rash.i Including skin hyperpigmentation and skin discolouration.j Including fatigue and asthenia.k Infusion-related reaction includes as any reaction (infusion-related reaction, pruritus and rash) occurring withinthe same day as Datroway infusion.
Description of selected adverse reactionsInterstitial lung disease/pneumonitis
ILD/pneumonitis occurred in 4.7% of the pool of patients with breast cancer treated with Datroway6 mg/kg, of which 3.6% were adjudicated as drug-related ILD/pneumonitis by independent review.
Most ILD/pneumonitis cases were Grade 1 (2.9%). Grade 2 events occurred in 0.9% of patients.
Grade 3 events occurred in 0.9% of patients. Adjudicated drug-related Grade 5 events occurred in0.2% of patients. Median time to first onset was 5.8 months (range: 1.1 to 10.8).
Ocular surface undesirable effects
Ocular surface undesirable effects occurred in 49.0% of the pool of patients treated with Datroway, ofwhich 35.0% were Grade 1, 12.2% were Grade 2 and 1.8% were Grade 3. Keratitis occurred in 17.8%of the pool of patients treated with Datroway, of which 13.3% were Grade 1, 3.6% were Grade 2 and0.9% were Grade 3. The median time to onset was 4.1 months (range: 0 to 23.2). Discontinuation dueto keratitis occurred in 0.5% of patients.
Stomatitis
Stomatitis occurred in 64.8% of the pool of patients treated with Datroway, of which 29.3% were
Grade 1, 27.5% were Grade 2 and 7.9% were Grade 3. Median time to first onset was 0.6 months(range: 0.03 to 12.2). Discontinuation due to stomatitis occurred in 0.5% of patients.
Haematological events
In study TROPION-Breast01 neutropenia occurred in 11.7% of patients treated with Datroway (1.1%were Grade ≥3). Leukopenia occurred in 3.6% of patients treated with Datroway (none were
Grade ≥3). Colony stimulating factor was used by 2.7% of patients treated with Datroway.
ElderlyOf the 443 patients with breast cancer treated with Datroway 6 mg/kg, 23.3% were 65 years or olderand 4.7% were 75 years or older. Data are limited to establish the safety in patients 85 years or older.
There was a numerically lower proportion of Grade 3/4 adverse reactions (24.3% vs 25.0%) and anumerically higher proportion of serious adverse reactions (9.7% vs 6.8%) and adverse reactionsleading to discontinuation (3.9% vs 3.5%) observed in patients aged 65 years or older compared topatients younger than 65 years old.
Reporting of suspected adverse reactionsReporting suspected adverse reactions after authorisation of the medicinal product is important. Itallows continued monitoring of the benefit/risk balance of the medicinal product. Healthcareprofessionals are asked to report any suspected adverse reactions via the national reporting systemlisted in Appendix V.
4.9 Overdose
There is currently no specific treatment in the event of an overdose. Higher than the indicated dosingmay increase risk of adverse reactions. Physicians should follow general supportive measures andinstitute appropriate treatment.
5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Antineoplastic agents, monoclonal antibodies and antibody drugconjugates, ATC code: L01FX35
Mechanism of actionDatopotamab deruxtecan is a TROP2-directed antibody-drug conjugate. The antibody is a humanisedanti-TROP2 IgG1 attached to deruxtecan, a topoisomerase I inhibitor (DXd) bound by atetrapeptide-based cleavable linker. The antibody-drug conjugate is stable in plasma. The antibodybinds to TROP2 expressed on the surface of certain tumour cells. After binding, datopotamabderuxtecan undergoes internalisation into the tumour cells. Subsequently, the release of DXd results in
DNA damage and apoptotic cell death via topoisomerase I inhibition. Datopotamab deruxtecan mayalso exhibit indirect cytotoxicity as shown in vitro through mechanisms of antibody-dependent cellularcytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP) and bystander cytotoxicity of
DXd against TROP2 expressing tumour cells and neighbouring cells.
Pharmacodynamic effectsImmunogenicity
As with all therapeutic proteins, there is a potential for immunogenicity.
During the median 5.5 month treatment period across clinical studies in NSCLC and breast cancerpatients treated with Datroway at 6 mg/kg, the incidence of anti-datopotamab deruxtecan antibodieswas 16% (146 out of 912) and the incidence of neutralising antibodies against datopotamab deruxtecanwas 2.5% (23 out of 912). There was no apparent effect of anti-drug antibodies on thepharmacokinetics or effectiveness of datopotamab deruxtecan. No clinically meaningful impact on thesafety of datopotamab deruxtecan was observed.
Clinical efficacy and safetyHR+/HER2- breast cancer
TROPION-Breast01 (NCT05104866)
The efficacy of Datroway was evaluated in study TROPION-Breast01, a multicentre, open-label,randomised study of 732 patients with unresectable or metastatic HR-positive, HER2-negative (IHC 0,
IHC1+ or IHC2+/ISH-) breast cancer. Patients must have progressed on and been unsuitable forendocrine therapy. Patients were required to have received 1 to 2 lines of prior chemotherapy in theunresectable or metastatic disease setting. Patients with clinically inactive brain metastases wereincluded in the study. Patients were excluded for a history of ILD/pneumonitis requiring treatmentwith steroids, ongoing ILD/pneumonitis, or clinically significant cardiac, pulmonary or corneal diseaseat screening. Patients were also excluded for Eastern Cooperative Oncology Group (ECOG)performance status > 1.
A total of 732 patients were randomised 1:1 to receive either Datroway 6 mg/kg (N=365) byintravenous infusion every 3 weeks or physician’s choice of chemotherapy (N=367, eribulin 59.9%,capecitabine 20.7%, vinorelbine 10.4% or gemcitabine 9.0%) until unacceptable toxicity or diseaseprogression. Randomisation was stratified by previous lines of chemotherapy (one or two), priortreatment with a CDK4/6 inhibitor (yes or no) and geographical region (United States, Canada,
Europe, or Rest of World). Tumour imaging was obtained every 6 weeks until disease progression.
The dual primary efficacy endpoints were progression-free survival (PFS) as assessed by blindedindependent central review (BICR) based on Response Evaluation Criteria in Solid Tumours(RECIST) v.1.1 and overall survival (OS). Confirmed objective response rate (ORR) and duration ofresponse (DOR) were secondary endpoints.
Baseline demographics and disease characteristics were similar between treatment arms. The medianage was 55 years (range 28 to 86); 22.3% were ≥ 65 years and 98.8% were female; 47.8% were White,1.5% were Black or African American, 40.7% were Asian and 11.3% were of Hispanic/Latinoethnicity; 57% had ECOG PS 0 and 42.3% had ECOG PS of 1; 97.3% had visceral disease, 71.9% hadliver metastases and 7.9% had stable brain metastases at baseline at the time of randomisation.
There were 60.2% of patients who received prior endocrine therapy in the (neo) adjuvant setting,88.5% received prior endocrine therapy in the unresectable or metastatic setting and all patientsreceived prior chemotherapy regimens in the unresectable or metastatic setting. Overall, 80.7% ofpatients had received prior taxanes and 63.8% had received prior anthracyclines. There were 62% ofpatients who had 1 prior chemotherapy regimen and 37.7% of patients who had 2 prior chemotherapyregimens for treatment of unresectable or metastatic disease. 82.5% of patients had prior treatmentwith a CDK4/6 inhibitor.
Efficacy results are shown in Table 4 and Figure 1 and 2.
Table 4: Efficacy results in TROPION-Breast01
Efficacy parameter Datroway Chemotherapy(N=365) (N=367)
Progression-free survival by BICRa
Number of events (%) 212 (58.1) 235 (64.0)
Median, months (95% CI) 6.9 (5.7, 7.4) 4.9 (4.2, 5.5)
Hazard ratio (95% CI) 0.63 (0.52, 0.76)p-valueb < 0.0001
Overall Survivalc, d
Number of events (%) 223 (61.1) 213 (58.0)
Median, months (95% CI) 18.6 (17.3, 20.1) 18.3 (17.3, 20.5)
Hazard ratio (95% CI) 1.01 (0.83, 1.22)p-valuee 0.9445
Objective response rate by BICRa, fn (%) 133 (36.4) 84 (22.9)95% CI 31.4, 41.3 18.6, 27.2
Duration of response by BICRa, f
Median, months (95% CI) 6.7 (5.6, 9.8) 5.7 (4.9, 6.8)a Data cutoff 17 July 2023b Predefined p-value boundary was 0.01.c Data cutoff 24 July 2024d 12.3% and 24.0% of patients in the datopotamab deruxtecan and ICC arms, respectively, received subsequenttreatment with trastuzumab deruxtecan and/or sacituzumab govitecan post discontinuation.e Predefined p-value boundary was 0.0403.f Endpoints were analysed descriptively.
Figure 1: Kaplan-Meier plot of PFS by BICR in TROPION-Breast01 (data cutoff 17 July 2023)
Censored
Datopotamab deruxtecan (N=365)
ICC (N=367)
Numbers at Risk Time Since Randomisation (Months)
Datopotamabderuxtecan (N=365)
ICC (N=367)
The improvement in PFS by BICR was consistent amongst the prespecified subgroups of patientsincluding by geographic region, prior use of CDK4/6 inhibitor and previous line of therapy.
Figure 2: Kaplan-Meier plot of final OS in TROPION-Breast01 (data cutoff 24 July 2024)
Censored
Datopotamab deruxtecan (N=365)
ICC (N=367)
Time Since Randomisation (Months)
Number at risk
Datopotamab deruxtecan (N=365)
ICC (N=367
Paediatric populationThe European Medicines Agency has waived the obligation to submit the results of studies with
Datroway in all subsets of the paediatric population in breast cancer (see section 4.2 for informationon paediatric use).
5.2 Pharmacokinetic properties
The pharmacokinetics of datopotamab deruxtecan was evaluated in 729 patients.
At the recommended dosage of Datroway, the geometric mean (coefficient of variation [CV]%) Cmaxof datopotamab deruxtecan and DXd were 154 µg/mL (20.3%) and 2.82 ng/mL (58.1%), respectively,and the AUC (area under the plasma concentration versus time curve) of datopotamab deruxtecan and
DXd were 671 µg*day/mL (31.4%) and 18.5 ng*day/mL (42.6%) after the first dose in cycle 1,respectively.
Overall Survival (%)
Progression-free Survival (%)
DistributionSteady state volume of distribution of datopotamab deruxtecan is 3.52 L. In vitro, across theconcentration range of 10 ng/mL to 100 ng/mL, the mean human plasma protein binding of DXd was96.8 to 98.0%, and the blood-to-plasma concentration ratio of DXd was 0.59-0.62.
BiotransformationDatopotamab deruxtecan undergoes intracellular cleavage by lysosomal enzymes to release DXd. Thehumanised TROP2 IgG1 monoclonal antibody is expected to be degraded into small peptides andamino acids via catabolic pathways in the same manner as endogenous IgG. In vitro metabolismstudies in human liver microsomes indicate that DXd is primarily metabolised by CYP3A4 viaoxidative pathways and does not undergo significant metabolism by UGT or other CYP enzymes.
EliminationFollowing intravenous administration of datopotamab deruxtecan in patients, the clearance ofdatopotamab deruxtecan was estimated to be 0.57 L/day. The median elimination half-life (t1/2) ofdatopotamab deruxtecan was 4.82 days and apparent median t1/2 of released DXd was approximately5.50 days. In vitro, DXd was a substrate of P-gp, OATP1B1, OATP1B3, MATE2-K, MRP1 and
BCRP. DXd excretion was not studied in humans.
In vitro interactions
Effects of Datroway on the pharmacokinetics of other medicinal products
In vitro studies indicate DXd does not inhibit or induce major CYP450 enzymes including CYP1A2,2B6, 2C8, 2C9, 2C19, 2D6 and 3A. In vitro studies indicate that DXd does not inhibit OAT1, OAT3,
OCT1, OCT2, OATP1B1, OATP1B3, MATE1, MATE2-K, P-gp, BCRP or BSEP transporters.
Effects of other medicinal products on the pharmacokinetics of Datroway
In vitro, DXd was a substrate of P-gp, OATP1B1, OATP1B3, MATE2-K, MRP1 and BCRP.
No clinically meaningful interaction is expected with medicinal products that are inhibitors of
MATE2-K, MRP1, P-gp, OATP1B1 or BCRP transporters (see section 4.5).
Linearity/non-linearityThe exposure of datopotamab deruxtecan and released DXd when administered intravenouslyincreased in proportion to dose in the 4 mg/kg to 10 mg/kg dose range (approximately 0.7 to 1.7 timesthe recommended dose). No accumulation of datopotamab deruxtecan was observed at the 6 mg/kgdose between cycle 1 and cycle 3.
Special populationsBased on population pharmacokinetic analysis, age (26 to 86 years), race, region, and sex did not havea clinically meaningful effect on exposure of datopotamab deruxtecan or DXd. The mean volume ofdistribution and clearance of datopotamab deruxtecan and DXd increase with increasing body weight(35.6 kg to 156 kg). This is considered clinically relevant. See section 4.2 for dose recommendations.
Renal impairmentNo dedicated renal impairment study was conducted. Based on population pharmacokinetic analysisincluding patients with mild to moderate (CLcr ≥ 30 and <90 mL/min) renal impairment (estimated by
Cockcroft-Gault), the pharmacokinetics of datopotamab deruxtecan or DXd was not affected by mildto moderate renal impairment as compared to normal renal function (CLcr ≥ 90 mL/min) (seesection 4.2).
Hepatic impairmentNo dedicated hepatic impairment study was conducted. Based on population pharmacokinetic analysisincluding patients with mild hepatic impairment (total bilirubin ≤ ULN and any AST > ULN or totalbilirubin > 1 to 1.5 times ULN and any AST), the pharmacokinetics of datopotamab deruxtecan or
DXd was not affected by mild hepatic impairment as compared to normal hepatic function. There arelimited data in patients with moderate (total bilirubin > 1.5 to 3 times ULN and any AST) hepaticimpairment to draw conclusions. Insufficient data are available for patients with severe (total bilirubin> 3 times ULN and any AST) hepatic impairment. Therefore, patients with moderate and severehepatic impairment should be monitored carefully (see section 4.2 and 4.4).
5.3 Preclinical safety data
Repeat-dose toxicity
In animals, toxicities were observed in lymphatic and haematopoietic organs, intestines, kidneys, maleand female reproductive tracts, lung, skin, eye (cornea), liver and incisor teeth following theadministration of datopotamab deruxtecan at exposure levels of the topoisomerase I inhibitor belowclinical plasma exposure. In these animals, ADC exposure levels were similar or above clinical plasmaexposure.
GenotoxicityDXd was clastogenic in both an in vivo rat bone marrow micronucleus assay and an in vitro Chinesehamster lung chromosome aberration assay.
CarcinogenicityCarcinogenicity studies have not been conducted with datopotamab deruxtecan.
Reproductive and developmental toxicityDedicated fertility studies have not been conducted with datopotamab deruxtecan. Based on the resultsfrom an animal toxicity study in rats, datopotamab deruxtecan at 200 mg/kg (approximately 29 timesthe human recommended dose of 6 mg/kg based on AUC) may impair male and female reproductivefunction and fertility at exposure levels of the topoisomerase I inhibitor below clinical plasmaexposure. Toxicity to male reproductive tract included testis (degeneration of germinal epithelium andatrophy of seminiferous tubule) and epididymis (single cell necrosis of ductal epithelium, cell debris induct and decreased number of spermatozoa in duct), which did not reverse after 8 weeks of treatmentcessation, except for single cell necrosis of ductal epithelium. The effects on female fertility, includingan increase in the number of atretic follicles in the ovaries and single cell necrosis of mucosalepithelium in the vagina, may be reversible.
Reproductive and developmental toxicity studies have not been conducted with datopotamabderuxtecan. Based on results from general animal toxicity studies, datopotamab deruxtecan and DXdwere toxic to rapidly dividing cells (testes), and DXd was genotoxic, suggesting the potential forembryotoxicity and teratogenicity.
6. PHARMACEUTICAL PARTICULARS
6.1 List of excipients
L-histidine
L-histidine hydrochloride monohydrate
Sucrose
Polysorbate 80 (E 433)
6.2 Incompatibilities
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinalproducts.
Sodium chloride solution for infusion must not be used for reconstitution or dilution since it may causeparticulate formation.
6.3 Shelf life
Unopened vial4 years.
Reconstituted solutionChemical and physical in-use stability has been demonstrated for up to 48 hours at 2 °C to 8 °C. Froma 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 notbe longer than 24 hours at 2 °C to 8 °C, unless reconstitution has taken place in controlled andvalidated aseptic conditions.
Diluted solutionIt is recommended that the diluted solution be used immediately. If not used immediately, the dilutedsolution may be stored at room temperature (≤ 25 °C) for up to 4 hours or in a refrigerator at2 °C to 8 °C for up to 24 hours, including preparation and infusion, protected from light.
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-resinlaminated 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 aphysician 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 ofreconstituted Datroway solution required, and the number of vial(s) of Datroway needed (seesection 4.2).
* Reconstitute each 100 mg vial using a sterile syringe to slowly inject 5 mL of water for injectioninto each vial to obtain a final concentration of 20 mg/mL.
* Swirl the vial gently until completely dissolved. Do not shake.
* From a microbiological point of view, the product should be used immediately. If not usedimmediately, chemical and physical in-use stability has been demonstrated for up to 48 hours at2 ºC to 8 ºC. Store the reconstituted Datroway vials in a refrigerator at 2 °C to 8 °C, protectedfrom light. Do not freeze.
* The reconstituted product contains no preservative and is intended for single use only.
Dilution* Withdraw the calculated amount from the vial(s) using a sterile syringe. Inspect thereconstituted solution for particulates and discolouration. The solution should be clear andcolourless to light yellow. Do not use if visible particles are observed or if the solution is cloudyor discoloured.
* Dilute the calculated volume of reconstituted Datroway in an infusion bag containing 100 mL of5% glucose solution. Do not use sodium chloride solution (see section 6.2). An infusion bagmade of polyvinylchloride (PVC) or polyolefin (polypropylene (PP) or copolymer of ethyleneand 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 includingpreparation and infusion, or in a refrigerator at 2 °C to 8 °C for up to 24 hours, protected fromlight. Do not freeze.
* Discard any unused portion left in the vial.
Administration* If the prepared infusion solution was stored refrigerated (2 °C to 8 °C), it is recommended thatthe solution be allowed to reach to room temperature prior to administration, protected fromlight.
* Administer Datroway as an intravenous infusion only with an infusion line and tubing set madeof 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 productsthrough the same intravenous line.
DisposalAny unused medicinal product or waste material should be disposed of in accordance with localrequirements.
10. DATE OF REVISION OF THE TEXT
Detailed information on this medicinal product is available on the website of the European Medicines
Agency https://www.ema.europa.eu.