SAFETY

DATROWAY has serious Warnings and Precautions. Click here for more information.

Safety data from TROPION-Breast01 demonstrated the benefit-risk profile of DATROWAY^1,2

The majority of common adverse reactions with DATROWAY were Grade 1 or 2

Adverse reactions (≥10%) in patients who received DATROWAY in TROPION-Breast01¹

Adverse reactions, %		All Grades	Grades 3 or 4	All Grades	Grades 3 or 4
		DATROWAY (n=360)		Chemotherapy (n=351)
Gastrointestinal disorders	Stomatitis*	59	7	17	2.6
	Nausea	56	1.4	27	0.6
	Constipation	34	0.3	17	0
	Vomiting	24	1.1	12	1.1
	Diarrhea	11	0.6	19	1.4
	Abdominal pain*	11	0.6	15	1.4
General disorders	Fatigue^†	44	4.2	40	3.7
Skin and subcutaneous tissue disorders	Alopecia	38	0	22	0
Skin and subcutaneous tissue disorders	Rash*	19	0	17	2.3
Eye disorders	Dry eye	27	0.8	13	0
Eye disorders	Keratitis^‡	24	1.1	10	0
Metabolism and nutrition disorders	Decreased appetite	16	1.4	16	0.9
Infections and infestations	COVID-19*	16	1.4	13	0.9
Respiratory, thoracic, and mediastinal disorders	Cough*	15	0	10	0

Adverse reactions, %	All Grades	Grades 3 or 4	All Grades	Grades 3 or 4
	DATROWAY (n=360)		Chemotherapy (n=351)
Gastrointestinal disorders
Stomatitis*	59	7	17	2.6
Nausea	56	1.4	27	0.6
Constipation	34	0.3	17	0
Vomiting	24	1.1	12	1.1
Diarrhea	11	0.6	19	1.4
Abdominal pain*	11	0.6	15	1.4
General disorders
Fatigue^†	44	4.2	40	3.7
Skin and subcutaneous tissue disorders
Alopecia	38	0	22	0
Rash*	19	0	17	2.3
Eye disorders
Dry eye	27	0.8	13	0
Keratitis^‡	24	1.1	10	0
Metabolism and nutrition disorders
Decreased appetite	16	1.4	16	0.9
Infections and infestations
COVID-19*	16	1.4	13	0.9
Respiratory, thoracic, and mediastinal disorders
Cough*	15	0	10	0

Events were graded using National Cancer Institute Common Terminology Criteria (NCI CTCAE) version 5.0.¹

*Includes other related terms.¹

^†Includes fatigue, asthenia, lethargy, malaise.¹

^‡Includes corneal disorder, corneal erosion, corneal infiltrates, corneal lesion, corneal toxicity, injury corneal, keratitis, keratopathy, punctate keratitis, and ulcerative keratitis.¹

Grade ≥3 TRAEs^1,2

21%

with DATROWAY

45%

with chemotherapy

Serious adverse reactions occurred in 15% of patients with DATROWAY

Discontinuation rate due to ARs¹

with DATROWAY

Dosage interruptions and dose reductions of DATROWAY due to ARs occurred in 22% and 23% of patients, respectively

TRAEs refer to adverse events possibly related to treatment as assessed by the investigator. Adverse reactions refer to adverse events which have a likely basis for a causal relationship between the drug and the occurrence of the adverse event.^2,3

Grade ≥3 neutropenia was 1% with DATROWAY and 31% with chemotherapy. 3% of patients on DATROWAY and 22% of patients on chemotherapy required G-CSF treatment.²

Select TRAEs in TROPION-Breast01^2,4-6

In TROPION-Breast01, the majority of select TRAEs with DATROWAY were Grade 1 or 2

Select TRAEs, %	Grade 1	Grade 2	Grade ≥3	Discontinuation rate	Grade 1	Grade 2	Grade ≥3	Discontinuation rate
	DATROWAY (n=360)				Chemotherapy (n=351)
Stomatitis	25	23	7	0.3	9	3.4	2.6	0
Adjudicated drug-related ILD^§	1.4	1.1	0.8	1.4	0	0	0	0
Keratitis^¶	11	2.5	0.6	0	4	0.9	0	0
Dry eye	19	1.9	0.6	0.3	7	0.9	0	0
Alopecia	21	15	0	0	10	10	0	0

Select TRAEs, %	DATROWAY (n=360)
Select TRAEs, %	Grade 1	Grade 2	Grade ≥3	Discontinuation rate
Stomatitis	25	23	7	0.3
Adjudicated drug-related ILD^d	1.4	1.1	0.8	1.4
Keratitis	11	2.5	0.6	0
Dry eye	19	1.9	0.6	0.3
Alopecia	21	15	0	0

	Grade 1	Grade 2	Grade ≥3	Discontinuation rate
	Chemotherapy (n=351)
Stomatitis	9	3.4	2.6	0
Adjudicated drug-related ILD^§	0	0	0	0
Keratitis^¶	4	0.9	0	0
Dry eye	7	0.9	0	0
Alopecia	10	10	0	0

TRAEs refer to adverse events possibly related to treatment as assessed by the investigator.

^§One patient had an adjudicated drug-related Grade 5 ILD event with DATROWAY.²

^¶Includes keratitis, punctate keratitis, and ulcerative keratitis.

Defining Grade 1-2 select adverse reactions
Stomatitis^6#

Grade 1: Asymptomatic or mild symptoms

Grade 2: Moderate pain or ulcer that does not interfere with oral intake; modified diet indicated

ILD/pneumonitis^1,6#

Grade 1: Asymptomatic; consider corticosteroid treatment

Grade 2: Symptomatic; promptly initiate corticosteroid treatment; limiting instrumental activities of daily living

Keratitis^6#

Grade 1: Asymptomatic; clinical or diagnostic observations only

Grade 2: Symptomatic; moderate decrease in visual acuity**

Dry eye^6||

Grade 1: Asymptomatic or mild symptoms; clinical or diagnostic observations only; symptoms relieved by lubricants

Grade 2: Symptomatic; moderate decrease in visual acuity**

Alopecia^6||

Grade 1: Hair loss of <50%^††

Grade 2: Hair loss of ≥50% normal for individual; readily apparent to others^‡‡

^#Grades are based on both the NCI CTCAE and the full Prescribing Information for DATROWAY.

^||Grades are based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0.

**Best corrected visual ability 20/40 and better or 3 lines or less decreased vision from known baseline.⁶

^††A different hair style may be required to cover the hair loss but does not require a wig or hair piece to camouflage.⁶

^‡‡A wig or hairpiece is necessary if the patient desires to completely camouflage the hair loss; associated with psychological impact.⁶

Grades shown here do not encompass all grades included in NCI CTCAE. Please refer to guidance on DATROWAY dosing modifications and adverse reaction management.

Warnings and Precautions¹

The pooled safety population described in the WARNINGS AND PRECAUTIONS reflects exposure to DATROWAY in 927 patients from TROPION-Breast01 and other clinical trials.

ILD/pneumonitis (unresectable or metastatic breast cancer)^§§

In the pooled safety population of 443 patients with breast cancer from TROPION-Breast01 and TROPION-PanTumor01, 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 was 2.8 months (range: 1.1-10.8 months). Four patients (0.9%) had DATROWAY withheld and 7 patients (1.6%) permanently discontinued due to ILD/pneumonitis

Ocular adverse reactions (unresectable or metastatic breast cancer and other solid tumors)

DATROWAY can cause ocular ARs including dry eye, keratitis, blepharitis, meibomian gland dysfunction, increased lacrimation, conjunctivitis, and blurred vision
In the pooled safety population, ocular ARs occurred in 36% of patients treated with DATROWAY. Twenty patients (2.2%) experienced Grade 3 ocular ARs, 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 ARs were dry eye (17%), keratitis (14%), and increased lacrimation (7%). The median time to onset was 2.3 months (range: 0.03-23.2 months). Ocular ARs led to dosage interruption in 3.6%, dosage reductions in 2.5% of patients, and permanent discontinuation in 1% of patients

Stomatitis (unresectable or metastatic breast cancer and other solid tumors)

DATROWAY can cause stomatitis, including mouth ulcers and oral mucositis
In the pooled safety population, 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: 0.03-18.6 months). Stomatitis led to dosage interruption in 6%, dosage reductions in 11%, and permanent discontinuation in 0.5% of patients

Embryo-fetal toxicity

DATROWAY can cause embryo-fetal harm

^§§A higher incidence of ILD/pneumonitis has been observed in patients with mild and moderate renal impairment (creatinine clearance [CLcr] 30 to <90 mL/min).¹

Additional safety data for DATROWAY in TROPION-Breast01¹
Median duration of treatment was 6.7 months (range: 0.7-16.1 months).

Serious adverse reactions

Serious adverse reactions (>0.5% of patients) were urinary tract infection (1.9%), COVID-19 infection (1.7%), ILD/pneumonitis (1.1%), acute kidney injury, pulmonary embolism, vomiting, diarrhea, hemiparesis, and anemia (0.6% each). Fatal adverse reactions occurred in 0.3% of patients and were due to ILD/pneumonitis

Adverse reactions associated with discontinuations and dose modifications

Discontinuation (>0.5% of patients) included ILD/pneumonitis (1.7%) and fatigue (0.6%)

Dosage interruption (>1% of patients) included COVID-19 (3.3%), infusion-related reaction (1.4%), ILD/pneumonitis (1.9%), stomatitis (1.9%), fatigue (1.7%), keratitis (1.4%), acute kidney injury (1.1%), and pneumonia (1.1%)

Dose reduction (>1% of patients) included stomatitis (13%), fatigue (3.1%), nausea (2.5%), and weight decrease (1.9%)

Other clinically relevant adverse reactions in <10% of patients

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

Select laboratory abnormalities (≥20%) in patients who received DATROWAY in TROPION-Breast01¹

Laboratory abnormality, %		All Grades	Grades 3 or 4	All Grades	Grades 3 or 4
		DATROWAY (n=360)^¶¶		Chemotherapy (n=351)^¶¶
Hematology	Decreased leukocytes	41	1.1	63	18
	Decreased lymphocytes	36	9	42	11
	Decreased hemoglobin	35	2.8	51	4.4
	Decreased neutrophils	30	1.6	61	35
Chemistry	Decreased calcium	39	1.4	43	1.2
	Increased AST	23	1.9	28	0.9
	Increased ALT	24	1.7	31	0.6
	Increased alkaline phosphate	23	0.6	20	0.6

Laboratory abnormality, %	All Grades	Grades 3 or 4	All Grades	Grades 3 or 4
	DATROWAY (n=360)^¶¶		Chemotherapy (n=351)^¶¶
Hematology
Decreased leukocytes	41	1.1	63	18
Decreased lymphocytes	36	9	42	11
Decreased hemoglobin	35	2.8	51	4.4
Decreased neutrophils	30	1.6	61	35
Chemistry
Decreased calcium	39	1.4	43	1.2
Increased AST	23	1.9	28	0.9
Increased ALT	24	1.7	31	0.6
Increased alkaline  phosphate	23	0.6	20	0.6

^¶¶The denominator used to calculate the rate varied from 264 to 359 based on the number of patients with a baseline value and at least one post-treatment value. Frequencies were based on NCI CTCAE v.5.0 grade-derived laboratory abnormalities¹

ADC, antibody-drug conjugate; ALT, alanine aminotransferase; ARs, adverse reactions; AST, aspartate aminotransferase; BICR, blinded independent central review; CDK, cyclin-dependent kinase; CI, confidence interval; ET, endocrine therapy; HER2−, human epidermal growth factor receptor 2-negative; HR, hazard ratio; HR+, hormone receptor-positive; IHC, immunohistochemistry; ISH, in situ hybridization; IV, intravenous; mBC, metastatic breast cancer; mPFS, median progression-free survival; OS, overall survival; PFS, progression-free survival; Q3W, once every three weeks; TRAEs, treatment-related adverse events; Trop-2, trophoblast cell-surface antigen 2.

2L+, second-line or later; ADC, antibody-drug conjugate; ASCO/CAP, American Society of Clinical Oncology/College of American Pathologists; BICR, blinded independent central review; CDK, cyclin-dependent kinase; DCR, disease control rate; DoR, duration of response; ECOG, Eastern Cooperative Oncology Group; ET, endocrine therapy; HER2−, human epidermal growth factor receptor 2-negative; HR+, hormone receptor-positive; ICC, investigator's choice of chemotherapy; IHC, immunohistochemistry; ISH, in situ hybridization; IV, intravenous; mBC, metastatic breast cancer; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; PS, performance status; Q3W, once every three weeks; Trop-2, trophoblast cell-surface antigen 2.

BICR, blinded independent central review; CDK, cyclin-dependent kinase; Cl, confidence interval; CR, complete response; DCR, disease control rate; DoR, duration of response; ECOG, Eastern Cooperative Oncology Group; ET, endocrine therapy; HER2−, human epidermal growth factor receptor 2-negative; HR, hazard ratio; HR+, hormone receptor-positive; mBC, metastatic breast cancer; mOS, median overall survival; mPFS, median progression-free survival; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; PR, partial response; RECIST, Response Evaluation Criteria in Solid Tumours; SD, stable disease.

ADC, antibody-drug conjugate; ALT, alanine aminotransferase; ARs, adverse reactions; AST, aspartate aminotransferase; CLcr, creatinine clearance; G-CSF, granulocyte-colony stimulating factor; HER2−, human epidermal growth factor receptor 2-negative; HR+, hormone receptor-positive; ILD, interstitial lung disease; mBC, metastatic breast cancer; NCI CTCAE, National Cancer Institute Common Terminology Criteria for Adverse Events; Q3W, once every three weeks; TRAEs, treatment-related adverse events; Trop-2, trophoblast cell-surface antigen 2.

ADC, antibody-drug conjugate; HER2−, human epidermal growth factor receptor 2-negative; HR+, hormone receptor-positive; IHC, immunohistochemistry; ISH, in situ hybridization; IV, intravenous; Q3W, once every three weeks; Trop-2, trophoblast cell-surface antigen 2.

5-HT3, 5-hydroxytryptamine type 3; HER2−, human epidermal growth factor receptor 2-negative; HR+, hormone receptor-positive; ILD, interstitial lung disease; Trop-2, trophoblast cell-surface antigen 2.

DNA, deoxyribonucleic acid; HER2−, human epidermal growth factor receptor 2-negative; HR+, hormone receptor-positive; mAb, monoclonal antibody; Trop-2, trophoblast cell-surface antigen 2.

HER2−, human epidermal growth factor receptor 2-negative; HR+, hormone receptor-positive.

INDICATION AND IMPORTANT SAFETY INFORMATION

WARNING: INTERSTITIAL LUNG DISEASE AND EMBRYO-FETAL TOXICITY

Severe and fatal cases of ILD/pneumonitis have been reported with DATROWAY. Monitor for and promptly investigate signs and symptoms including cough, dyspnea, fever, and other new or worsening respiratory symptoms. Permanently discontinue in all patients with Grade 2 or higher ILD/pneumonitis. Advise patients of the risk and to immediately report symptoms.
Exposure to DATROWAY during pregnancy can cause embryo-fetal harm. Advise patients of these risks and the need for effective contraception.

INDICATION

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.

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

CONTRAINDICATIONS

None.

WARNINGS AND PRECAUTIONS

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, 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.

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.

Ocular Adverse Reactions

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

Locally Advanced or Metastatic NSCLC and Other Solid Tumors

In patients with locally advanced or metastatic NSCLC and other solid tumors, 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.

Stomatitis

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

Locally Advanced or Metastatic NSCLC and Other Solid Tumors

In patients with locally advanced or metastatic NSCLC and other solid tumors, 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.

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.

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, is genotoxic and affects actively dividing cells.

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.

ADVERSE REACTIONS

Locally Advanced or Metastatic NSCLC and Other Solid Tumors

The pooled safety population described in WARNINGS AND PRECAUTIONS reflects exposure to DATROWAY 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 927 patients in TROPION-Lung05, TROPION-Lung01, TROPION-PanTumor01, and other clinical trials. Among these patients who received DATROWAY, 45% were exposed for 6 months or longer and 19% were exposed for greater than one year. In this pooled safety population, the most common (≥ 20%) adverse reactions were stomatitis (63%), nausea (52%), fatigue (45%), alopecia (38%), constipation (28%), decreased appetite (23%), rash (23%), vomiting (22%), and musculoskeletal pain (20%). In this pooled safety population, the most common (≥2%) Grade 3 or 4 laboratory abnormalities were decreased lymphocytes (9%) and decreased hemoglobin (3.5%).

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. Among these patients, the median duration of treatment was 6.1 months (range 0.7 months to 41.7 months).

The median age was 63 years (range: 36 to 81), 56% of patients were <65 years, 62% of patients were female; 66% were Asian, 26% were White, 0.8% were Black, 6% were other races; and 2.4% were of Hispanic ethnicity.

Serious adverse reactions occurred in 26% of patients who received DATROWAY. Serious adverse reactions in >1% of patients who received DATROWAY were COVID-19 (4%), stomatitis (2.4%), and pneumonia (1.6%). 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. Adverse reactions which required dosage interruption in >1% of patients included COVID-19 (13%), stomatitis (7%), fatigue (6%), pneumonia (4%), anemia (2.4%), amylase increased (2.4%), keratitis (2.4%), ILD/pneumonitis (1.6%), decreased appetite (1.6%), dyspnea (1.6%), rash (1.6%), and infusion-related reaction (1.6%).

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 (14%), keratitis (1.6%), fatigue (1.6%), decreased weight (1.6%) and COVID-19 (1.6%).

The most common (≥20%) adverse reactions, including laboratory abnormalities, were stomatitis (71%), nausea (50%), alopecia (49%), fatigue (42%), decreased hemoglobin (34%), decreased lymphocytes (32%), constipation (31%), increased calcium (31%), increased AST (28%), decreased white blood cell count (27%), increased lactate dehydrogenase (23%), musculoskeletal pain (22%), decreased appetite (20%), increased ALT (20%), and rash (20%).

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.

USE IN SPECIFIC POPULATIONS

Pregnancy: 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.
Lactation: 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.
Females and Males of Reproductive Potential: 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. 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.
Pediatric Use: Safety and effectiveness of DATROWAY have not been established in pediatric patients.
Geriatric Use: Of the 125 patients with EGFR-mutated NSCLC in TROPION-Lung05, TROPION-Lung01, TROPION-PanTumor01 treated with DATROWAY 6 mg/kg, 44% were ≥65 years of age and 10% were ≥75 years of age. No clinically meaningful differences in efficacy and safety were observed between patients ≥65 years of age versus younger patients.
Renal Impairment: A higher incidence of ILD/pneumonitis has been observed in patients with mild and moderate renal impairment (creatinine clearance [CLcr] 30 to <90 mL/min). Monitor patients with renal impairment for increased adverse reactions, including respiratory reactions. No dosage adjustment is recommended in patients with mild to moderate renal impairment. The effect of severe renal impairment (CLcr <30 mL/min) on the pharmacokinetics of datopotamab deruxtecan-dlnk or DXd is unknown.
Hepatic Impairment: No dosage adjustment is recommended in patients with mild hepatic impairment (total bilirubin ≤ULN and any AST >ULN or total bilirubin >1 to 1.5 times ULN and any AST). Limited data are available in patients with moderate hepatic impairment (total bilirubin >1.5 to 3 times ULN and any AST). Monitor patients with moderate hepatic impairment for increased adverse reactions. The recommended dosage of DATROWAY has not been established for patients with severe hepatic impairment (total bilirubin >3 times ULN and any AST).

To report SUSPECTED ADVERSE REACTIONS, contact Daiichi Sankyo, Inc. at 1-877-437-7763 or FDA at 1-800-FDA-1088 or fda.gov/medwatch.

Please click here for full Prescribing Information, including WARNINGS AND PRECAUTIONS, and click here for Medication Guide.

2L+=second-line or later; ADC=antibody-drug conjugate; BICR=blinded independent central review; CDK=cyclin-dependent kinase; DCR=disease control rate; DoR=duration of response; ECOG=Eastern Cooperative Oncology Group; ET=endocrine therapy; HER2−=human epidermal growth factor receptor 2-negative; HR+=hormone receptor-positive; IHC=immunohistochemistry; ISH=in situ hybridization; IV=intravenous; mBC=metastatic breast cancer; ORR=objective response rate; OS=overall survival; PFS=progression-free survival; PS=performance status; Q3W=once every three weeks; Trop-2=trophoblast cell-surface antigen 2.

ADC=antibody-drug conjugate; BICR=blinded independent central review; CDK=cyclin-dependent kinase; Cl=confidence interval; CR=complete response; DCR=disease control rate; DoR=duration of response; ECOG=Eastern Cooperative Oncology Group; ET=endocrine therapy; HER2−=human epidermal growth factor receptor 2-negative; HR=hazard ratio; HR+=hormone receptor-positive; mBC=metastatic breast cancer; mOS=median overall survival; mPFS=median progression-free survival; ORR=objective response rate; OS=overall survival; PFS=progression-free survival; PR=partial response; RECIST=Response Evaluation Criteria in Solid Tumours; SD=stable disease.

ADC=antibody-drug conjugate; HER2−=human epidermal growth factor receptor 2-negative; HR+=hormone receptor-positive; IHC=immunohistochemistry; ISH=in situ hybridization; IV=intravenous; Q3W=once every three weeks; Trop-2=trophoblast cell-surface antigen 2.

DNA=deoxyribonucleic acid; HER2−=human epidermal growth factor receptor 2-negative; HR+=hormone receptor-positive; mAb=monoclonal antibody; Trop-2=trophoblast cell-surface antigen 2.

HER2−=human epidermal growth factor receptor 2-negative; HR+=hormone receptor-positive.

INDICATION

CONTRAINDICATIONS

None.

Safety data from TROPION-Breast01 demonstrated the benefit-risk profile of DATROWAY1,2

The majority of common adverse reactions with DATROWAY were Grade 1 or 2

Grade ≥3 TRAEs1,2

Discontinuation rate due to ARs1

Select TRAEs in TROPION-Breast012,4-6

In TROPION-Breast01, the majority of select TRAEs with DATROWAY were Grade 1 or 2

NOW APPROVED for locally advanced or metastatic EGFRm NSCLC

Safety data from TROPION-Breast01 demonstrated the benefit-risk profile of DATROWAY^1,2

Grade ≥3 TRAEs^1,2

Discontinuation rate due to ARs¹

Select TRAEs in TROPION-Breast01^2,4-6