Datroway

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.

3 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.

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

Summary of safety profile The pooled safety profile has been assessed from two clinical studies involving 443 patients who received Datroway 6 mg/kg body weight for the treatment of breast cancer. 5 months). 4%). 1%). 7% of patients and were due to ILD/pneumonitis, dyspnoea and sepsis.

1%). 6%. 0%). 0%. 4%). 6%. 1%). Tabulated list of adverse reactions Table 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 adverse event frequencies, where a proportion of the events for an adverse reaction may have other causes than datopotamab deruxtecan, such as the disease, other medicinal products or unrelated causes.

The severity 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 (cannot be estimated from the available data).

Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness. 9 Table 3: Adverse reactions in patients treated with datopotamab deruxtecan 6 mg/kg System organ class Frequency category Adverse reactions Infections and infestations Very common COVID-19a Common urinary tract infection, pneumoniab, sepsis Blood and lymphatic system disorders Very common anaemia, neutropeniac Common leukopenia Immune system disorders Not known anaphylactic reaction Metabolism and nutrition disorders Very common decreased appetite Nervous system disorders Common dysgeusia Eye disorders Very common keratitisd, dry eye Common conjunctivitise, blurred vision, lacrimation increased, blepharitis, meibomian gland dysfunction, photophobia Uncommon visual impairment Respiratory, thoracic and mediastinal disorders Common ILD/pneumonitisf, dyspnoea Gastrointestinal disorders Very common stomatitisg, vomiting, nausea, diarrhoea, constipation Common dry mouth Skin and subcutaneous tissue disorders Very common alopecia, rashh Common pruritus, dry skin, skin hyperpigmentationi, madarosis General disorders and administration site conditions Very common fatiguej Investigations Very common aspartate aminotransferase increased, alanine aminotransferase increased Injury, poisoning and procedural complications Common infusion-related reactionk a Including COVID-19, COVID-19 pneumonia, SARS-CoV-2 test positive.

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.

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.

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. 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.

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.

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