Datroway Drug Information

Patient Selection

Select patients with locally advanced or metastatic NSCLC for treatment with DATROWAY based on the presence of epidermal growth factor receptor (EGFR) mutations in tumor or plasma specimens. Testing may be performed at any time from initial diagnosis and does not need to be repeated once EGFR mutation status has been established.

Recommended Dosage

The recommended dosage of DATROWAY is 6 mg/kg (up to a maximum of 540 mg for patients ≥90 kg) administered as an intravenous infusion once every 3 weeks (21-day cycle) until disease progression or unacceptable toxicity. If a planned dose is delayed or missed, administer as soon as possible; do not wait until the next planned cycle. Adjust the schedule of administration to maintain a 3-week interval between doses.

Premedication, Concomitant Medications, and Required Eye Care Conduct an ophthalmic exam including visual acuity testing, slit lamp examination (with fluorescein staining), intraocular pressure, and fundoscopy at initiation of DATROWAY, at end of treatment, and as clinically indicated. While on treatment, conduct visual acuity testing and slit lamp examination every 3 cycles. Administer DATROWAY with the premedication and concomitant medications described in Table 1.

Monitor patients for infusion-related reactions in a setting where cardiopulmonary resuscitation medication and equipment are available. Monitor patients for at least 1 hour for the first 2 cycles of DATROWAY infusions. If there are no infusion-related reactions observed, monitor patients for at least 30 minutes for all subsequent cycles of infusions.

Table 1: Premedication and Concomitant Medications s The recommended dose reduction levels for adverse reactions are described in Table 2. Table 2: Recommended Dosage Reductions of DATROWAY for Do not re-escalate the DATROWAY dose after a dose reduction. Permanently discontinue DATROWAY in patients who are unable to tolerate 3 mg/kg intravenously once every 3 weeks.

The recommended dosage modifications and management of adverse reactions for DATROWAY are described in Table 3. Table 3: Dosage Modifications and Management of Adverse Reactions for DATROWAY Adverse Reaction Severity Toxicity grades are in accordance with National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. Dosage Modifications Interstitial Lung Disease (ILD)/Pneumonitis

Preparation and Administration Reconstitute and further dilute DATROWAY prior to intravenous infusion. Use appropriate aseptic technique. DATROWAY (datopotamab deruxtecan-dlnk) is a hazardous drug.

Follow applicable special handling and disposal procedures. 1 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.

Reconstitute each 100 mg vial using a sterile syringe to slowly inject 5 mL of Sterile 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, refrigerate the reconstituted DATROWAY solution in the original vial at 2°C to 8°C (36°F to 46°F) for up to 48 hours from the time of reconstitution. Protect the vial from light. Do not freeze.

The product does not contain a preservative. Discard unused reconstituted DATROWAY after 48 hours of refrigeration. Dilution Withdraw the calculated amount from the vial(s) using a sterile syringe.

Inspect for particulate matter and discoloration prior to administration. The reconstituted solution should be clear and colorless to light yellow. Do not use if visible particles are observed or if the solution is cloudy or discolored.

Dilute the calculated volume of reconstituted DATROWAY in an infusion bag containing 100 mL of 5% Dextrose Injection. DO NOT use Sodium Chloride Injection. DATROWAY is compatible with an infusion bag made of polyvinylchloride or polyolefin (polypropylene or copolymer of ethylene and propylene).

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 at up to 25°C (77°F) for up to 4 hours including preparation or in a refrigerator at 2°C to 8°C (36°F to 46°F) for up to 24 hours. 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 48 hours. Discard if storage time exceeds these limits. If the prepared infusion solution was stored refrigerated at 2°C to 8°C (36°F to 46°F), allow the solution to reach room temperature prior to administration, protected from light.

Administer DATROWAY as an intravenous infusion only with an infusion line and tubing set made of polyvinyl chloride, polybutadiene or low-density polyethylene. Administer DATROWAY with a 0.2-micron in-line polytetrafluoroethylene, polyethersulfone or nylon 66 filter. Do NOT administer as an intravenous push or bolus.

Do not mix DATROWAY with other drugs or administer other drugs through the same intravenous line. Instruct the patient to hold ice chips or ice water in the mouth throughout the infusion of DATROWAY. First infusion: Administer infusion over 90 minutes.

Observe patients during the infusion and for at least 1 hour following the initial dose for signs or symptoms of infusion-related reactions. Second Infusion: If first infusion was tolerated, administer second infusion over 30 minutes. Subsequent Infusions: Administer infusion over 30 minutes if prior infusions were tolerated.

Observe patients during the infusion and for at least 30 min after infusion.

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The pooled safety population described in WARNINGS AND PRECAUTIONS reflects exposure to DATROWAY in 1365 patients as a single agent at 6 mg/kg administered as an intravenous infusion once every 3 weeks (21-day cycle) until disease progression or unacceptable toxicity. In this pooled safety population, the most common (≥ %).

Locally Advanced or Metastatic EGFR-Mutated Non-Small Cell Lung Cancer TROPION-Lung05, TROPION-Lung01, TROPION-PanTumor01 The safety of DATROWAY was evaluated in 125 patients with EGFR-mutated NSCLC who received DATROWAY 6 mg/kg administered as an intravenous infusion once every 3 weeks (21-day cycle) until disease progression or unacceptable toxicity in TROPION-Lung05 and TROPION-Lung01 as well as TROPION-PanTumor01 (NCT03401385). Among these patients, the median duration of treatment was 6.1 months (range 0.7 months to 41.7 months). Serious adverse reactions occurred in 26% of patients who received DATROWAY.

Fatal adverse reactions occurred in 1.6% of patients who received DATROWAY, due to death not otherwise specified. Permanent discontinuation of DATROWAY due to an adverse reaction occurred in 8% of patients. Adverse reactions which resulted in permanent discontinuation of DATROWAY in >1% of patients included ILD/pneumonitis (2.4%) and abnormal hepatic function (1.6%).

Dosage interruptions of DATROWAY due to an adverse reaction occurred in 43% of patients. Dose reductions of DATROWAY due to an adverse reaction occurred in 26% of patients. Adverse reactions which required dose reduction in >1% of patients included stomatitis ( %) adverse reactions, including laboratory abnormalities, were stomatitis, nausea, alopecia, fatigue, decreased hemoglobin, decreased lymphocytes, constipation, increased calcium, increased AST, decreased white blood cell count, increased lactate dehydrogenase, musculoskeletal pain, decreased appetite, increased ALT, and rash.

Table 4: Adverse Reactions (≥10%) in Patients with Locally Advanced or Metastatic EGFR-Mutated NSCLC Who Received DATROWAY in TROPION-Lung05, TROPION-Lung01, and TROPION-PanTumor01 0 Clinically relevant adverse reactions occurring in <10% of patients who received DATROWAY included dry skin, blurred vision, abdominal pain, conjunctivitis, dry mouth, ILD/pneumonitis, skin hyperpigmentation, increased lacrimation, and visual impairment. Table 5: Select Laboratory Abnormalities (≥20%) that Worsened from Baseline in Patients with Locally Advanced or Metastatic EGFR-Mutated NSCLC Who Received DATROWAY in TROPION-Lung05, TROPION-Lung01, and TROPION-PanTumor01 Unresectable or Metastatic Triple-Negative Breast Cancer (TNBC) TROPION-Breast02 The safety of DATROWAY was evaluated in 319 patients with triple-negative breast cancer who received at least one dose of DATROWAY 6 mg/kg in TROPION-Breast02. DATROWAY was administered by intravenous infusion once every three weeks.

The median duration of treatment was 8.5 months (range: 0.7 months to 38.0 months) for patients who received DATROWAY. Fatal adverse reactions occurred in one patient (0.3%) who received DATROWAY and was due to ILD/pneumonitis. Adverse reactions which resulted in permanent discontinuation of DATROWAY in >0.5% of patients included ILD/pneumonitis (0.9%) and keratitis (0.9%).

The most common (≥20%) adverse reactions, including laboratory abnormalities in patients receiving DATROWAY, were stomatitis, increased amylase, nausea, alopecia, decreased hemoglobin, decreased white blood cells, constipation, decreased calcium, decreased lymphocytes, fatigue, decreased neutrophils, increased ALT, increased AST, dry eye, keratitis, decreased albumin, vomiting, musculoskeletal pain, decreased sodium, and increased blood alkaline phosphatase. Table 6: Adverse Reactions (≥10%) in Patients Who Received DATROWAY in TROPION-Breast02 Clinically relevant adverse reactions occurring in <10% of patients who received DATROWAY included infusion-related reactions including anaphylactic reaction, diarrhea, conjunctivitis, lacrimation increased, dry mouth, dry skin, pruritus, rhinorrhea, blepharitis, meibomian gland dysfunction, blurred vision, ILD/pneumonitis, visual impairment, photophobia, and madarosis. Table 7: Select Laboratory Abnormalities (≥20%) in Patients Who Received DATROWAY in TROPION-Breast02 0 Unresectable or Metastatic, HR-Positive, HER2-Negative Breast Cancer TROPION-Breast01 The safety of DATROWAY was evaluated in 360 patients with unresectable or metastatic HR-positive, HER2-negative (IHC 0, IHC1+ or IHC2+/ISH-) breast cancer who received at least one dose of DATROWAY 6 mg/kg in TROPION-Breast01.

The median duration of treatment was 6.7 months (range: 0.7 months to 16.1 months) for patients who received DATROWAY. Fatal adverse reactions occurred in 0.3% of patients who received DATROWAY and were due to ILD/pneumonitis. Adverse reactions which resulted in permanent discontinuation of DATROWAY in >0.5% of patients included ILD/pneumonitis (1.7%) and fatigue (0.6%).

Adverse reactions which required dosage interruption in >1% of patients included %. Table 8: Adverse Reactions (≥10%) in Patients Who Received DATROWAY in TROPION-Breast01 0 Clinically relevant adverse reactions occurring in <10% of patients who received DATROWAY included infusion-related reactions (including bronchospasm), ILD/pneumonitis, headache, pruritus, dry skin, dry mouth, conjunctivitis, blepharitis, meibomian gland dysfunction, blurred vision, increased lacrimation, photophobia, visual impairment, skin hyperpigmentation, and madarosis.

Pregnancy Risk Summary Based on its mechanism of action, DATROWAY can cause embryo-fetal harm when administered to a pregnant woman because the topoisomerase inhibitor component of DATROWAY, DXd, is genotoxic and affects actively dividing cells. There are no available data on the use of DATROWAY in pregnant women to inform a drug-associated risk. Advise patients of the potential risks to a fetus.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is respectively. Data Animal Data There were no animal reproductive or developmental toxicity studies conducted with datopotamab deruxtecan-dlnk.

Pediatric Use Safety and effectiveness of DATROWAY have not been established in pediatric patients.