Datroway Datopotamab Deruxtecan for Injection

1. Indications and Usage
Non-Small Cell Lung Cancer (NSCLC):
Treatment of adult patients with locally advanced or metastatic NSCLC with epidermal growth factor receptor (EGFR) mutations, who have received prior EGFR tyrosine kinase inhibitor (TKI) therapy and platinum-based chemotherapy.
Breast Cancer:
Treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative unresectable or metastatic breast cancer who have received endocrine-based therapy and at least one line of systemic chemotherapy in the metastatic setting or in the neoadjuvant/adjuvant setting.
2. Dosage and Administration
Route of Administration:
For Intravenous (IV) Infusion ONLY. Do not administer as an intravenous push or bolus.
Reconstitution and Dilution:
Reconstitute with Sterile Water for Injection.
Dilute in 5% Dextrose Injection (D5W) only. Do not use 0.9% Sodium Chloride Injection.
Recommended Dosage:
Standard Dose: 6 mg/kg (actual body weight) administered every 3 weeks (21-day cycle).
Max Dose: For patients with actual body weight ≥90 kg, the maximum dose is 540 mg.
Critical Administration Instructions:
Infusion Time: Administer over 90 minutes for the first infusion. If the first infusion is tolerated, subsequent infusions may be administered over 60 minutes.
Pre-medication: Administer an antiemetic prior to infusion to reduce the risk of nausea and vomiting.
3. Mechanism of Action
Targeted Delivery:
Datopotamab Deruxtecan consists of a humanized anti-TROP-2 IgG1 monoclonal antibody linked to a cytotoxic topoisomerase I inhibitor (DXd) via a cleavable tetrapeptide-based linker.
Cytotoxic Effect:
Binding & Internalization: Binds to TROP-2 on the tumor cell surface and is internalized into the tumor cell.
Payload Release: The linker is cleaved by lysosomal enzymes, releasing the active DXd payload.
DNA Damage: DXd inhibits topoisomerase I, leading to DNA damage and apoptotic cell death.
Bystander Effect: The released payload can penetrate adjacent tumor cells, killing neighboring cells regardless of TROP-2 expression levels.
4. Safety and Warnings
Interstitial Lung Disease (ILD) / Pneumonitis:
Can cause severe, life-threatening, or fatal ILD/pneumonitis.
Action: Monitor for signs (cough, dyspnea). Interrupt or discontinue immediately if suspected.
Embryo-Fetal Toxicity:
Can cause fetal harm. Advise females of reproductive potential to use effective contraception.
Ocular Toxicity:
Can cause keratitis, dry eye, and conjunctivitis. Recommend regular ophthalmologic exams and lubricating eye drops.
stomatitis (Mucositis):
Can cause oral mucositis and stomatitis. Prophylactic steroid mouthwash and cryotherapy (ice chips) during infusion are recommended.
5.Adverse Reactions and Clinical Research
Most Common Adverse Reactions:
Stomatitis, nausea, alopecia, fatigue, diarrhea, decreased appetite, vomiting, and dry eye.
Clinical Research Highlights:
NSCLC: In the TROPION-Lung01 trial, Dato-DXd demonstrated a statistically significant improvement in progression-free survival (PFS) compared to docetaxel in previously treated EGFR-mutated NSCLC patients.
Breast Cancer: In the TROPION-Breast01 trial, it significantly improved PFS compared to chemotherapy in HR+/HER2- metastatic breast cancer patients.
6.Drug Interactions
No Specific CYP Interactions:
As an ADC, it is not a substrate of CYP enzymes, but monitoring is advised when combined with other toxic therapies.
7.Pharmaceutical Information
Chemical Composition:
Active Ingredient: Datopotamab Deruxtecan.
Appearance: Lyophilized cake or powder, white to off-white.
Packaging: Single-dose vial (100 mg).
Storage: Store at 2°C to 8°C (36°F to 46°F).