Datroway

DATROWAY is a Trop-2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of:

• adult patients with locally advanced or metastatic epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) who have received prior EGFR-directed therapy and platinum-based chemotherapy. (
  1.1 Locally Advanced or Metastatic EGFR-Mutated Non-Small Cell Lung Cancer (NSCLC)

  DATROWAY is indicated for the treatment of adult patients with locally advanced or metastatic epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) who have received prior EGFR-directed therapy and platinum-based chemotherapy.

  This indication is approved under accelerated approval based on objective response rate and duration of response

  [see Clinical Studies (14.1)]

  . Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trial.
  )
  
  This indication is approved under accelerated approval based on objective response rate and duration of response
  [see

  14.1 Locally Advanced or Metastatic EGFR-Mutated Non-Small Cell Lung Cancer

  The efficacy of DATROWAY was evaluated in a pooled subgroup of patients with locally advanced or metastatic EGFR-mutated NSCLC who were enrolled across two clinical studies: TROPION-Lung05 and TROPION-Lung01.

  TROPION-Lung05 (NCT04484142) was a global, multicenter, single-arm, open-label trial in patients with previously treated NSCLC with an actionable genomic alteration and TROPION-Lung01 (NCT04656652) was a global, multicenter, randomized, active-controlled, open-label trial in patients with previously treated NSCLC with or without an actionable genomic alteration. For both trials, eligible patients with EGFR-mutated NSCLC must have previously received an EGFR-directed therapy and platinum-based chemotherapy. Patients with a history of ILD/pneumonitis requiring treatment with steroids, ongoing ILD/pneumonitis, or clinically significant corneal disease at screening were ineligible. Patients who had brain metastases that were untreated and symptomatic were also ineligible. Patients received DATROWAY 6 mg/kg by intravenous infusion every 3 weeks until unacceptable toxicity or disease progression.

  For the pooled efficacy population, the major efficacy outcome measure was overall response rate (ORR) by BICR per RECIST v1.1. An additional efficacy outcome was duration of response (DOR) by BICR.

  Efficacy was assessed in 114 patients with EGFR-mutated NSCLC. The median age was 63 years (range 36 to 81); 43% were ≥65 years of age; 63% were female; 70% were Asian and 22% were White; 1.8% were of Hispanic/Latino ethnicity; 68% had ECOG PS of 1 and 32% had ECOG PS of 0; and 33% had brain metastases at baseline. Fifty-three percent (53%) of patients had tumors with exon 19 deletions, 34% had exon 21 L858R mutations, 28% had T790M mutations, 2.6% had exon 20 insertion mutations and 14% had other EGFR mutations. Four percent (4.4%) of patients received one prior line of systemic therapy, 39% received two prior lines of systemic therapy, and 57% received three or more prior lines of systemic therapy in the locally advanced or metastatic setting. All patients received prior EGFR-directed therapy including 84% receiving prior osimertinib; 99% received prior platinum-based chemotherapy and 28% received prior anti-PD-1/ PD-L1 therapy.

  Efficacy results are summarized in Table 9.

  Table 9: Efficacy Results in TROPION-Lung05 and TROPION-Lung01 by BICR

  	DATROWAY TL05 N=77	DATROWAY TL01 N=37	DATROWAY Pooled N=114
  CI: confidence interval
  Overall Response Rate (95% CI)	45% (34, 57)	43% (27, 61)	45% (35, 54)
  Complete Response	5%	2.7%	4.4%
  Partial Response	40%	41%	40%
  Duration of Response Median, months (95% CI)	6.9 (4.2, 10.2)	6.5 (4.0, 8.4)	6.5 (4.2, 8.4)
  ≥6 months	49%	44%	47%
  ≥12 months	23%	6%	18%

  In the TROPION-Lung05 trial, a difference was noted between ORR by BICR and ORR assessed by investigator; investigator assessed ORR was 34% (95% CI: 23, 45). In the TROPION-Lung01 trial, ORR assessed by investigator was similar to ORR by BICR.

  ]
  . Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trial.
• adult patients with unresectable or metastatic, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer who have received prior endocrine-based therapy and chemotherapy for unresectable or metastatic disease. (
  1.2 Unresectable or Metastatic, HR-Positive, HER2-Negative Breast Cancer

  DATROWAY is indicated for the treatment of adult patients with unresectable or metastatic, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer who have received prior endocrine-based therapy and chemotherapy for unresectable or metastatic disease.
  )

• Reconstitute DATROWAY with Sterile Water for Injection. (
  2.5 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
    [see Dosage and Administration (2.2)].
  • 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 2ºC to 8ºC (36°F to 46°F) for up to 24 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 24 hours refrigerated.

  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 25ºC (77°F) for up to 4 hours including preparation or in a refrigerator at 2ºC to 8ºC (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 24 hours. Discard if storage time exceeds these limits.
  • If the prepared infusion solution was stored refrigerated at 2ºC to 8ºC (36°F to 46°F), allow the solution to reach room temperature prior to administration, protected from light.
  • Inspect for particulate matter and discoloration prior to administration.
  • 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.
  • Cover the infusion bag to protect from light during administration.
  • 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. Observe patients during the infusion and for at least 1 hour after infusion.
  • 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.
  )
• Dilute with 5% Dextrose Injection. (
  2.5 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
    [see Dosage and Administration (2.2)].
  • 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 2ºC to 8ºC (36°F to 46°F) for up to 24 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 24 hours refrigerated.

  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 25ºC (77°F) for up to 4 hours including preparation or in a refrigerator at 2ºC to 8ºC (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 24 hours. Discard if storage time exceeds these limits.
  • If the prepared infusion solution was stored refrigerated at 2ºC to 8ºC (36°F to 46°F), allow the solution to reach room temperature prior to administration, protected from light.
  • Inspect for particulate matter and discoloration prior to administration.
  • 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.
  • Cover the infusion bag to protect from light during administration.
  • 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. Observe patients during the infusion and for at least 1 hour after infusion.
  • 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.
  )
• For intravenous infusion only. Do not administer as an intravenous push or bolus. DO NOT use Sodium Chloride Injection, USP. (
  2.5 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
    [see Dosage and Administration (2.2)].
  • 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 2ºC to 8ºC (36°F to 46°F) for up to 24 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 24 hours refrigerated.

  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 25ºC (77°F) for up to 4 hours including preparation or in a refrigerator at 2ºC to 8ºC (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 24 hours. Discard if storage time exceeds these limits.
  • If the prepared infusion solution was stored refrigerated at 2ºC to 8ºC (36°F to 46°F), allow the solution to reach room temperature prior to administration, protected from light.
  • Inspect for particulate matter and discoloration prior to administration.
  • 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.
  • Cover the infusion bag to protect from light during administration.
  • 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. Observe patients during the infusion and for at least 1 hour after infusion.
  • 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.
  )
• Premedicate to reduce the risk of infusion reactions and nausea and vomiting. (
  2.3 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, annually while on treatment, at end of treatment, and as clinically indicated.

  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

  PremedicationWith or without systemic corticosteroid	Examples (or equivalent)	Timing of Treatment/Duration
  Eye drops [see Warnings and Precautions (5.2)]	Preservative-free lubricant eye drops	Administer at least four times daily and as needed
  Mouthwash [see Warnings and Precautions (5.3)]	Steroid-containing mouthwash (dexamethasone oral solution 0.1 mg/mL)	Administer four times daily and as needed
  Antihistamine [see Adverse Reactions (6.1)]	Diphenhydramine (25 to 50 mg) administered intravenously or orally	Administer 30-60 minutes prior to each infusion
  Antipyretic [see Adverse Reactions (6.1)]	Acetaminophen (650 to 1,000 mg) administered intravenously or orally	Administer 30-60 minutes prior to each infusion
  Antiemetics [see Adverse Reactions (6.1)]	5-HT3 serotonin receptor antagonist or appropriate alternatives intravenously or oral	Prior to each infusion and thereafter as needed
  )
• The recommended dosage of DATROWAY is 6 mg/kg (up to a maximum of 540 mg for patients ≥90 kg) given as an intravenous infusion once every 3 weeks (21-day cycle) until disease progression or unacceptable toxicity. (
  2.3 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, annually while on treatment, at end of treatment, and as clinically indicated.

  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

  PremedicationWith or without systemic corticosteroid	Examples (or equivalent)	Timing of Treatment/Duration
  Eye drops [see Warnings and Precautions (5.2)]	Preservative-free lubricant eye drops	Administer at least four times daily and as needed
  Mouthwash [see Warnings and Precautions (5.3)]	Steroid-containing mouthwash (dexamethasone oral solution 0.1 mg/mL)	Administer four times daily and as needed
  Antihistamine [see Adverse Reactions (6.1)]	Diphenhydramine (25 to 50 mg) administered intravenously or orally	Administer 30-60 minutes prior to each infusion
  Antipyretic [see Adverse Reactions (6.1)]	Acetaminophen (650 to 1,000 mg) administered intravenously or orally	Administer 30-60 minutes prior to each infusion
  Antiemetics [see Adverse Reactions (6.1)]	5-HT3 serotonin receptor antagonist or appropriate alternatives intravenously or oral	Prior to each infusion and thereafter as needed
  ,
  2.4 Dosage Modifications

  Dosage Modifications for Adverse Reactions

  The recommended dose reduction levels for adverse reactions are described in Table 2.

  Table 2: Recommended Dosage Reductions of DATROWAY for Adverse Reactions

  Dose Reductions	Recommended Dose
  First	4 mg/kg (up to a maximum of 360 mg for patients ≥90 kg)
  Second	3 mg/kg (up to a maximum of 270 mg for patients ≥90 kg)
  Third	Permanently discontinue

  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	SeverityToxicity 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 [see Warnings and Precautions (5.1)]	Asymptomatic ILD/pneumonitis Grade 1	Withhold DATROWAY until ILD/pneumonitis is completely resolved, then: if resolved in ≤28 days, maintain current dose. if resolved in >28 days, reduce one dose level (see Table 2). Consider corticosteroids as soon as ILD/pneumonitis is suspected.
  	Symptomatic ILD/pneumonitis Grade 2 or greater	Permanently discontinue DATROWAY. Administer corticosteroids as soon as ILD/pneumonitis is suspected.
  Keratitis [see Warnings and Precautions (5.2)and Adverse Reactions (6.1)]	Nonconfluent superficial keratitis	Monitor. Continue DATROWAY at current dose.
  	Confluent superficial keratitis, a cornea epithelial defect, or 3-line or more loss in best corrected visual acuity	Withhold DATROWAY until improved or resolved Restart DATROWAY at the same dose level or consider dose reduction (see Table 2).
  	Corneal ulcer or stromal opacity or best corrected distance visual acuity 20/200 or worse	Withhold DATROWAY until improved or resolved Restart DATROWAY at reduced dose level (see Table 2).
  	Corneal perforation	Permanently discontinue DATROWAY.
  Stomatitis [see Warnings and Precautions (5.3)]	Grade 1	Optimize prophylactic and supportive medications. Continue DATROWAY at current dose.
  	Grade 2	Withhold DATROWAY until resolved to ≤Grade 1. Restart DATROWAY at the same dose level for first occurrence. Recurrence: consider restarting at reduced dose level (see Table 2).
  	Grade 3	Withhold DATROWAY until resolved to ≤Grade 1. Restart DATROWAY at reduced dose level (see Table 2).
  	Grade 4	Permanently discontinue DATROWAY.
  Infusion-Related Reactions (IRR) [see Adverse Reactions (6.1)]	Grade 1	Reduce DATROWAY infusion rate by 50% if IRR is suspected and monitor patient closely.
  	Grade 2	Interrupt DATROWAY infusion and administer supportive care medications. If the event resolves or improves to Grade 1, restart the infusion at 50% rate. Administer all subsequent infusions at the reduced rate.
  	Grade 3 or 4	Permanently discontinue DATROWAY.
  Other Non-Hematologic Adverse Reactions [see Adverse Reactions (6.1)]	Grade 3	Withhold dose until resolved to ≤Grade 1 or baseline Restart DATROWAY at reduced dose level (see Table 2).
  	Grade 4	Permanently discontinue DATROWAY.
  )

For injection: 100 mg of datopotamab deruxtecan-dlnk as a white to yellowish white, lyophilized powder in a single-dose vial for reconstitution and further dilution.

• Lactation: Advise not to breastfeed. (
  8.2 Lactation

  Risk Summary

  There are no data regarding the presence of datopotamab deruxtecan-dlnk or its metabolites in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with DATROWAY and for 1 month after the last dose.
  )
• Infertility: May impair fertility in males and females. (
  8.3 Females and Males of Reproductive Potential

  DATROWAY can cause embryo-fetal harm when administered to a pregnant woman

  [see Use in Specific Populations (8.1)].

  Pregnancy Testing

  Verify pregnancy status of females of reproductive potential prior to initiation of DATROWAY.

  Contraception

  Females

  Advise females of reproductive potential to use effective contraception during treatment with DATROWAY and for 7 months after the last dose.

  Males

  Because of the potential for genotoxicity, advise male patients with female partners of reproductive potential to use effective contraception during treatment with DATROWAY and for 4 months after the last dose

  [see Nonclinical Toxicology (13.1)]

  .

  Infertility

  Based on findings in animal toxicity studies, DATROWAY may impair male and female reproductive function and fertility. The effects on reproductive organs in animals were irreversible

  [see Nonclinical Toxicology (13.1)]

  .
  )

• Interstitial Lung Disease (ILD) and Pneumonitis:
  DATROWAY can cause severe and fatal cases of ILD/pneumonitis. Monitor for new or worsening signs and symptoms of ILD/pneumonitis. If ILD/pneumonitis is suspected, withhold DATROWAY and initiate corticosteroids. Permanently discontinue DATROWAY in patients with confirmed Grade 2 or higher ILD/pneumonitis. (
  5.1 Interstitial Lung Disease/Pneumonitis

  DATROWAY can cause severe, life-threatening, or fatal interstitial lung disease (ILD) or pneumonitis.

  Locally Advanced or Metastatic NSCLC

  In the pooled safety population of 484 patients with NSCLC from TROPION-Lung01, TROPION-Lung05, and TROPION-PanTumor01

  [see Adverse Reactions (6.1)],

  ILD/pneumonitis occurred in 7% of patients treated with DATROWAY, including 0.6% of patients with Grade 3 and 0.4% with Grade 4. There were 8 (1.7%) fatal cases. The median time to onset for ILD was 1.4 months (range: 0.2 months to 9 months). Eleven patients (2.3%) had DATROWAY withheld and 20 patients (4.1%) permanently discontinued DATROWAY due to ILD/pneumonitis. Systemic corticosteroids were required in 79% (26/33) of patients with ILD/pneumonitis. ILD/pneumonitis resolved in 45% of patients.

  Unresectable or Metastatic Breast Cancer

  In the pooled safety population of 443 patients with breast cancer from TROPION-Breast01 and TROPION-PanTumor01

  [see Adverse Reactions (6.1)],

  ILD/pneumonitis occurred in 3.6% of patients treated with DATROWAY, including 0.7% of patients with Grade 3. There was one fatal case (0.2%). The median time to onset for ILD was 2.8 months (range: 1.1 months to 10.8 months). Four patients (0.9%) had DATROWAY withheld and 7 patients (1.6%) permanently discontinued DATROWAY due to ILD/pneumonitis. Systemic corticosteroids were required in 60% (9/15) of patients with ILD/pneumonitis. ILD/pneumonitis resolved in 40% of patients.

  Patients were excluded from clinical studies for a history of ILD/pneumonitis requiring treatment with steroids or for ongoing ILD/pneumonitis.

  Monitor patients for new or worsening respiratory symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever) during treatment with DATROWAY. For asymptomatic (Grade 1) ILD/pneumonitis, consider corticosteroid treatment (e.g., ≥0.5 mg/kg/day prednisolone or equivalent). 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 gradual taper for at least 4 weeks.

  Withhold DATROWAY in patients with suspected ILD/pneumonitis and permanently discontinue DATROWAY if ≥Grade 2 ILD/pneumonitis is confirmed

  [see Dosage and Administration (2.4)].
  )
• Ocular Adverse Reactions:
  DATROWAY can cause ocular adverse reactions including dry eye, keratitis, blepharitis, meibomian gland dysfunction, increased lacrimation, conjunctivitis, and blurred vision. Monitor patients for ocular adverse reactions during treatment with DATROWAY. Advise patients to use preservative-free lubricating eye drops and to avoid using contact lenses during treatment with DATROWAY. Withhold, reduce the dose, or permanently discontinue DATROWAY based on the severity of ocular adverse reactions. Refer patients to an eye care professional for any new or worsening ocular signs and symptoms. (
  2.3 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, annually while on treatment, at end of treatment, and as clinically indicated.

  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

  PremedicationWith or without systemic corticosteroid	Examples (or equivalent)	Timing of Treatment/Duration
  Eye drops [see Warnings and Precautions (5.2)]	Preservative-free lubricant eye drops	Administer at least four times daily and as needed
  Mouthwash [see Warnings and Precautions (5.3)]	Steroid-containing mouthwash (dexamethasone oral solution 0.1 mg/mL)	Administer four times daily and as needed
  Antihistamine [see Adverse Reactions (6.1)]	Diphenhydramine (25 to 50 mg) administered intravenously or orally	Administer 30-60 minutes prior to each infusion
  Antipyretic [see Adverse Reactions (6.1)]	Acetaminophen (650 to 1,000 mg) administered intravenously or orally	Administer 30-60 minutes prior to each infusion
  Antiemetics [see Adverse Reactions (6.1)]	5-HT3 serotonin receptor antagonist or appropriate alternatives intravenously or oral	Prior to each infusion and thereafter as needed
  ,
  2.4 Dosage Modifications

  Dosage Modifications for Adverse Reactions

  The recommended dose reduction levels for adverse reactions are described in Table 2.

  Table 2: Recommended Dosage Reductions of DATROWAY for Adverse Reactions

  Dose Reductions	Recommended Dose
  First	4 mg/kg (up to a maximum of 360 mg for patients ≥90 kg)
  Second	3 mg/kg (up to a maximum of 270 mg for patients ≥90 kg)
  Third	Permanently discontinue

  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	SeverityToxicity 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 [see Warnings and Precautions (5.1)]	Asymptomatic ILD/pneumonitis Grade 1	Withhold DATROWAY until ILD/pneumonitis is completely resolved, then: if resolved in ≤28 days, maintain current dose. if resolved in >28 days, reduce one dose level (see Table 2). Consider corticosteroids as soon as ILD/pneumonitis is suspected.
  	Symptomatic ILD/pneumonitis Grade 2 or greater	Permanently discontinue DATROWAY. Administer corticosteroids as soon as ILD/pneumonitis is suspected.
  Keratitis [see Warnings and Precautions (5.2)and Adverse Reactions (6.1)]	Nonconfluent superficial keratitis	Monitor. Continue DATROWAY at current dose.
  	Confluent superficial keratitis, a cornea epithelial defect, or 3-line or more loss in best corrected visual acuity	Withhold DATROWAY until improved or resolved Restart DATROWAY at the same dose level or consider dose reduction (see Table 2).
  	Corneal ulcer or stromal opacity or best corrected distance visual acuity 20/200 or worse	Withhold DATROWAY until improved or resolved Restart DATROWAY at reduced dose level (see Table 2).
  	Corneal perforation	Permanently discontinue DATROWAY.
  Stomatitis [see Warnings and Precautions (5.3)]	Grade 1	Optimize prophylactic and supportive medications. Continue DATROWAY at current dose.
  	Grade 2	Withhold DATROWAY until resolved to ≤Grade 1. Restart DATROWAY at the same dose level for first occurrence. Recurrence: consider restarting at reduced dose level (see Table 2).
  	Grade 3	Withhold DATROWAY until resolved to ≤Grade 1. Restart DATROWAY at reduced dose level (see Table 2).
  	Grade 4	Permanently discontinue DATROWAY.
  Infusion-Related Reactions (IRR) [see Adverse Reactions (6.1)]	Grade 1	Reduce DATROWAY infusion rate by 50% if IRR is suspected and monitor patient closely.
  	Grade 2	Interrupt DATROWAY infusion and administer supportive care medications. If the event resolves or improves to Grade 1, restart the infusion at 50% rate. Administer all subsequent infusions at the reduced rate.
  	Grade 3 or 4	Permanently discontinue DATROWAY.
  Other Non-Hematologic Adverse Reactions [see Adverse Reactions (6.1)]	Grade 3	Withhold dose until resolved to ≤Grade 1 or baseline Restart DATROWAY at reduced dose level (see Table 2).
  	Grade 4	Permanently discontinue DATROWAY.
  ,
  5.2 Ocular Adverse Reactions

  DATROWAY can cause ocular adverse reactions including dry eye, keratitis, blepharitis, meibomian gland dysfunction, increased lacrimation, conjunctivitis, and blurred vision.

  In the pooled safety population

  [see Adverse Reactions (6.1)]

  , ocular adverse reactions occurred in 36% of patients treated with DATROWAY. Twenty patients (2.2%) experienced Grade 3 ocular adverse reactions, which included keratitis, dry eye, and blurred vision, and one patient experienced a Grade 4 ocular adverse reaction of conjunctival hemorrhage. The most common (≥5%) ocular adverse reactions were dry eye (17%), keratitis (14%), and increased lacrimation (7%). The median time to onset for ocular adverse reactions was 2.3 months (range: 0.03 months to 23.2 months). Of the patients who experienced ocular adverse reactions, 39% had complete resolution, and 10% had partial improvement (defined as a decrease in severity by one or more grades from the worst grade at last follow up). Ocular adverse reactions led to dosage interruption in 3.6% of patients, dosage reductions in 2.5% of patients, and permanent discontinuation of DATROWAY in 1% of patients.

  Patients with clinically significant corneal disease were excluded from clinical studies.

  Advise patients to use preservative-free lubricant eye drops several times daily for prophylaxis. Advise patients to avoid use of contact lenses unless directed by an eye care professional.

  Refer patients to an eye care professional for an ophthalmic exam including visual acuity testing, slit lamp examination (with fluorescein staining), intraocular pressure, and fundoscopy at treatment initiation, annually while on treatment, at end of treatment, and as clinically indicated.

  Promptly refer patients to an eye care professional for any new or worsening ocular adverse reactions. Monitor patients for ocular adverse reactions during treatment with DATROWAY, and if diagnosis is confirmed, withhold, reduce the dose, or permanently discontinue DATROWAY based on severity

  [see Dosage and Administration (2.4)]

  .
  )
• Stomatitis/Oral Mucositis:
  DATROWAY can cause stomatitis, including mouth ulcers and oral mucositis. Advise patients to use a steroid-containing mouthwash when starting treatment and to hold ice chips or ice water in mouth during the infusion of DATROWAY. Withhold, reduce the dose, or permanently discontinue DATROWAY based on severity. (
  2.3 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, annually while on treatment, at end of treatment, and as clinically indicated.

  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

  PremedicationWith or without systemic corticosteroid	Examples (or equivalent)	Timing of Treatment/Duration
  Eye drops [see Warnings and Precautions (5.2)]	Preservative-free lubricant eye drops	Administer at least four times daily and as needed
  Mouthwash [see Warnings and Precautions (5.3)]	Steroid-containing mouthwash (dexamethasone oral solution 0.1 mg/mL)	Administer four times daily and as needed
  Antihistamine [see Adverse Reactions (6.1)]	Diphenhydramine (25 to 50 mg) administered intravenously or orally	Administer 30-60 minutes prior to each infusion
  Antipyretic [see Adverse Reactions (6.1)]	Acetaminophen (650 to 1,000 mg) administered intravenously or orally	Administer 30-60 minutes prior to each infusion
  Antiemetics [see Adverse Reactions (6.1)]	5-HT3 serotonin receptor antagonist or appropriate alternatives intravenously or oral	Prior to each infusion and thereafter as needed
  ,
  2.4 Dosage Modifications

  Dosage Modifications for Adverse Reactions

  The recommended dose reduction levels for adverse reactions are described in Table 2.

  Table 2: Recommended Dosage Reductions of DATROWAY for Adverse Reactions

  Dose Reductions	Recommended Dose
  First	4 mg/kg (up to a maximum of 360 mg for patients ≥90 kg)
  Second	3 mg/kg (up to a maximum of 270 mg for patients ≥90 kg)
  Third	Permanently discontinue

  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	SeverityToxicity 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 [see Warnings and Precautions (5.1)]	Asymptomatic ILD/pneumonitis Grade 1	Withhold DATROWAY until ILD/pneumonitis is completely resolved, then: if resolved in ≤28 days, maintain current dose. if resolved in >28 days, reduce one dose level (see Table 2). Consider corticosteroids as soon as ILD/pneumonitis is suspected.
  	Symptomatic ILD/pneumonitis Grade 2 or greater	Permanently discontinue DATROWAY. Administer corticosteroids as soon as ILD/pneumonitis is suspected.
  Keratitis [see Warnings and Precautions (5.2)and Adverse Reactions (6.1)]	Nonconfluent superficial keratitis	Monitor. Continue DATROWAY at current dose.
  	Confluent superficial keratitis, a cornea epithelial defect, or 3-line or more loss in best corrected visual acuity	Withhold DATROWAY until improved or resolved Restart DATROWAY at the same dose level or consider dose reduction (see Table 2).
  	Corneal ulcer or stromal opacity or best corrected distance visual acuity 20/200 or worse	Withhold DATROWAY until improved or resolved Restart DATROWAY at reduced dose level (see Table 2).
  	Corneal perforation	Permanently discontinue DATROWAY.
  Stomatitis [see Warnings and Precautions (5.3)]	Grade 1	Optimize prophylactic and supportive medications. Continue DATROWAY at current dose.
  	Grade 2	Withhold DATROWAY until resolved to ≤Grade 1. Restart DATROWAY at the same dose level for first occurrence. Recurrence: consider restarting at reduced dose level (see Table 2).
  	Grade 3	Withhold DATROWAY until resolved to ≤Grade 1. Restart DATROWAY at reduced dose level (see Table 2).
  	Grade 4	Permanently discontinue DATROWAY.
  Infusion-Related Reactions (IRR) [see Adverse Reactions (6.1)]	Grade 1	Reduce DATROWAY infusion rate by 50% if IRR is suspected and monitor patient closely.
  	Grade 2	Interrupt DATROWAY infusion and administer supportive care medications. If the event resolves or improves to Grade 1, restart the infusion at 50% rate. Administer all subsequent infusions at the reduced rate.
  	Grade 3 or 4	Permanently discontinue DATROWAY.
  Other Non-Hematologic Adverse Reactions [see Adverse Reactions (6.1)]	Grade 3	Withhold dose until resolved to ≤Grade 1 or baseline Restart DATROWAY at reduced dose level (see Table 2).
  	Grade 4	Permanently discontinue DATROWAY.
  ,
  5.3 Stomatitis

  DATROWAY can cause stomatitis, including mouth ulcers and oral mucositis.

  In the pooled safety population

  [see Adverse Reactions (6.1)],

  stomatitis occurred in 63% of patients treated with DATROWAY, including 8% of patients with Grade 3 events and one patient with a Grade 4 reaction. The median time to first onset of stomatitis was 0.5 months (range: 0.03 months to 18.6 months). Stomatitis led to dosage interruption in 6% of patients, dosage reductions in 11% of patients, and permanent discontinuation of DATROWAY in 0.5% of patients.

  In patients who received DATROWAY in TROPION-Breast01, 39% used a mouthwash containing corticosteroid for management or prophylaxis of stomatitis/oral mucositis at any time during the treatment.

  Advise patients to use a steroid-containing mouthwash for prophylaxis and treatment of stomatitis. Instruct the patient to hold ice chips or ice water in the mouth throughout the infusion of DATROWAY.

  Monitor patients for signs and symptoms of stomatitis. If stomatitis occurs, increase the frequency of mouthwash and administer other topical treatments as clinically indicated. Based on the severity of the adverse reaction, withhold, reduce the dose, or permanently discontinue DATROWAY

  [see Dosage and Administration (2.4)].
  )
• Embryo-Fetal Toxicity
  : DATROWAY can cause fetal harm. Advise patients of potential risk to a fetus and to use effective contraception. (
  5.4 Embryo-Fetal Toxicity

  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

  [see Description (11)]

  , is genotoxic and affects actively dividing cells

  [see Use in Specific Populations (8.1), Clinical Pharmacology (12.1), Nonclinical Toxicology (13.1)].

  Advise patients of the potential risk to a fetus. Advise female patients of reproductive potential to use effective contraception during treatment with DATROWAY and for 7 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with DATROWAY and for 4 months after the last dose

  [see Use in Specific Populations (8.1, 8.3)].
  ,
  8.1 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

  [see Clinical Pharmacology (12.1), Nonclinical Toxicology (13.1)]

  . 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 2 to 4% and 15 to 20%, respectively.

  Data

  Animal Data

  There were no animal reproductive or developmental toxicity studies conducted with datopotamab deruxtecan-dlnk.
  ,
  8.3 Females and Males of Reproductive Potential

  DATROWAY can cause embryo-fetal harm when administered to a pregnant woman

  [see Use in Specific Populations (8.1)].

  Pregnancy Testing

  Verify pregnancy status of females of reproductive potential prior to initiation of DATROWAY.

  Contraception

  Females

  Advise females of reproductive potential to use effective contraception during treatment with DATROWAY and for 7 months after the last dose.

  Males

  Because of the potential for genotoxicity, advise male patients with female partners of reproductive potential to use effective contraception during treatment with DATROWAY and for 4 months after the last dose

  [see Nonclinical Toxicology (13.1)]

  .

  Infertility

  Based on findings in animal toxicity studies, DATROWAY may impair male and female reproductive function and fertility. The effects on reproductive organs in animals were irreversible

  [see Nonclinical Toxicology (13.1)]

  .
  )