PADCEV® (enfortumab vedotin-ejfv) 6 ADVERSE REACTIONS

(enfortumab vedotin-ejfv)

Prescribing Information

6 ADVERSE REACTIONS

The following serious adverse reactions are described elsewhere in the labeling:

•: Skin Reactions [see Boxed Warning, Warnings and Precautions (5.1)]
•: Hyperglycemia [see Warnings and Precautions (5.2)]
•: Pneumonitis/Interstitial Lung Disease (ILD) [see Warnings and Precautions (5.3)]
•: Peripheral Neuropathy [see Warnings and Precautions (5.4)]
•: Ocular Disorders [see Warnings and Precautions (5.5)]
•: Infusion Site Extravasation [see Warnings and Precautions (5.6)]

6.1 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 safety population described in the WARNINGS AND PRECAUTIONS reflect exposure to PADCEV 1.25 mg/kg in combination with intravenous pembrolizumab for the treatment of MIBC in 570 patients in EV-303 (NCT03924895) and EV-304 (NCT04700124) and for the treatment of la/mUC in 564 patients in EV-302 (NCT04223856) and EV-103 (NCT03288545); PADCEV as a single agent at 1.25 mg/kg in 720 patients in EV-301 (NCT03474107), EV‑201 (NCT03219333), EV-203 (NCT04995419), EV-101 (NCT02091999), and EV-102 (NCT03070990). Ocular disorders reflect 384 patients in EV‑201, EV-101, and EV-102.

Among 570 patients receiving PADCEV in combination with intravenous pembrolizumab for the treatment of MIBC, the most common (≥20%) adverse reactions, including laboratory abnormalities, were decreased hemoglobin, increased aspartate aminotransferase, increased alanine aminotransferase, rash, increased creatinine, decreased lymphocytes, fatigue, pruritus, decreased sodium, peripheral neuropathy, increased potassium, diarrhea, alopecia, dysgeusia, decreased appetite, nausea, constipation, urinary tract infection, dry eye, increased glucose, decreased weight, decreased potassium, hyperglycemia, decreased phosphate, and decreased neutrophils.

Among 564 patients receiving PADCEV in combination with intravenous pembrolizumab for the treatment of la/mUC, 59% were exposed to PADCEV for ≥6 months, and 24% were exposed for ≥12 months. In this pooled population, the most common (≥20%) adverse reactions, including laboratory abnormalities, were increased aspartate aminotransferase, increased creatinine, rash, increased glucose, peripheral neuropathy, increased lipase, decreased lymphocytes, increased alanine aminotransferase, decreased hemoglobin, fatigue, decreased sodium, decreased phosphate, decreased albumin, pruritus, diarrhea, alopecia, decreased weight, decreased appetite, increased urate, decreased neutrophils, decreased potassium, dry eye, nausea, constipation, increased potassium, dysgeusia, urinary tract infection, and decreased platelets.

Among 720 patients receiving PADCEV as a single agent, 37% were exposed for ≥6 months, and 14% were exposed for ≥12 months. In this pooled population, the most common (≥20%) adverse reactions, including laboratory abnormalities, were increased glucose, increased aspartate aminotransferase, decreased lymphocytes, increased creatinine, rash, fatigue, peripheral neuropathy, decreased albumin, decreased hemoglobin, alopecia, decreased appetite, decreased neutrophils, decreased sodium, increased alanine aminotransferase, decreased phosphate, diarrhea, nausea, pruritus, increased urate, dry eye, dysgeusia, constipation, increased lipase, decreased weight, decreased platelets, abdominal pain, and dry skin.

The data described in the following section reflects exposure to PADCEV in combination with intravenous pembrolizumab from EV‑302, the dose escalation cohort, Cohort A and Cohort K of EV-103, EV-303, and EV-304. Patients from EV-302 and EV-103 received PADCEV 1.25 mg/kg in combination with intravenous pembrolizumab until disease progression or unacceptable toxicity. Patients from EV-303 and EV-304 received PADCEV 1.25 mg/kg in combination with intravenous pembrolizumab for 9 cycles or until disease progression or unacceptable toxicity.

The data described in the following section also reflects exposure to PADCEV as a single agent from an open-label, randomized, trial (EV‑301) and Cohort 1 and Cohort 2 of an open-label, single arm, two cohort trial (EV-201). Patients received PADCEV 1.25 mg/kg until disease progression or unacceptable toxicity.

Neoadjuvant and Adjuvant Treatment of Patients with MIBC Who Are Cisplatin-Eligible

EV-304

The safety of PADCEV in combination with intravenous pembrolizumab as neoadjuvant treatment and continued after radical cystectomy (RC) as adjuvant treatment was evaluated in an open-label, randomized, active-controlled, multicenter trial (EV-304) in patients with previously untreated MIBC who were eligible for cisplatin-based chemotherapy. Patients received either PADCEV 1.25 mg/kg in combination with intravenous pembrolizumab (n=403) before and after RC with pelvic lymph node dissection (PLND) or chemotherapy (gemcitabine with cisplatin) before RC with PLND (n=396) [see Clinical Studies (14)].

For the 403 patients who received PADCEV in the neoadjuvant phase, the median duration of exposure to PADCEV was 2.3 months (range: 0.03 to 4 months) and the median number of cycles of PADCEV was 4 (range: 1, 4) in the neoadjuvant phase. Out of 262 patients who received adjuvant treatment in the PADCEV in combination with pembrolizumab arm, 225 patients received PADCEV. The median duration of exposure to PADCEV was 3 months (range: 0.03 to 18.3 months) and the median number of cycles of PADCEV was 5 (range: 1, 5) for patients who received PADCEV in the adjuvant phase. Across the combined neoadjuvant and adjuvant phases (n=403), the median number of cycles of PADCEV was 6 (range: 1, 9) out of a planned 9 cycles.

Table 5 summarizes the most common (≥20%) adverse reactions in EV-304.

Table 5. Adverse Reactions ≥20% (All Grades) in Patients Treated with PADCEV in Combination with Intravenous Pembrolizumab in EV-304
* Graded per NCI CTCAE v5.0. † Includes multiple terms.
Adverse Reaction	Perioperative PADCEV in combination with intravenous pembrolizumab n=403		Neoadjuvant Gemcitabine with Cisplatin n=396
Adverse Reaction	All Grades* %	Grade 3-4 %	All Grades* %	Grade 3-4 %
Skin and subcutaneous tissue disorders
Rash†	63	12	9	0.3
Pruritus	46	3.2	4.5	0
Alopecia	32	0.5	11	0
General disorders and administration site conditions
Fatigue†	48	2.7	49	2.3
Nervous system disorders
Peripheral neuropathy†	43	3	11	0.8
Dysgeusia†	28	0.2	10	0
Gastrointestinal disorders
Diarrhea†	36	3.2	16	1.3
Nausea	28	1	47	0.5
Constipation	27	0.7	37	0.5
Metabolism and nutrition disorders
Decreased appetite	29	1	18	0.5
Hyperglycemia†	20	7	7	0.8
Infections and Infestations
Urinary tract infection	25	10	21	10
Eye disorders
Dry eye†	25	0	1.3	0
Investigations
Decreased weight	22	2.5	6	0.3

Clinically relevant adverse reactions (<20%) include dry skin (16%), vomiting (13%), hypothyroidism (12%), pneumonitis/ILD (8%), skin hyperpigmentation (3.5%), myositis (0.7%), infusion site extravasation (0.5%), and myasthenia gravis (0.2%).

Table 6. Selected Laboratory Abnormalities Reported in ≥20% (All Grades) of Patients Treated with PADCEV in Combination with Intravenous Pembrolizumab in EV-304
* The denominator used to calculate the rate of PADCEV in combination with intravenous pembrolizumab varied from 399 to 403 and the denominator used to calculate the rate for chemotherapy varied from 388 to 393 based on the number of patients with a baseline value and at least one post-treatment value. † Graded per NCI CTCAE v5.0.
Laboratory Abnormality*	Perioperative PADCEV in combination with intravenous pembrolizumab		Neoadjuvant Gemcitabine with Cisplatin
Laboratory Abnormality*	All Grades† %	Grade 3-4 %	All Grades† %	Grade 3-4 %
Hematology
Decreased hemoglobin	70	8	92	20
Decreased lymphocytes	52	17	46	11
Decreased neutrophils	32	13	75	40
Chemistry
Increased aspartate aminotransferase	69	7	23	0.5
Increased alanine aminotransferase	67	8	30	0
Increased creatinine	49	8	53	6
Decreased sodium	43	4.2	39	1.3
Decreased albumin	42	3.3	36	1.8
Increased potassium	35	4.7	31	5
Decreased potassium	22	3	20	2.8

Neoadjuvant Phase of EV-304

A total of 403 patients received at least one dose of PADCEV in combination with intravenous pembrolizumab as neoadjuvant treatment before receiving RC.

In the neoadjuvant phase, serious adverse reactions occurred in 27% of patients receiving PADCEV in combination with intravenous pembrolizumab. The most common serious adverse reactions (≥1.5%) were rash (3.2%), pneumonitis/ILD (2.2%), and diarrhea (1.7%). Fatal adverse reactions occurred in 1.7% of patients, including multiple organ dysfunction syndrome (0.5%) and COVID-19 pneumonia, cardiac arrest, pneumonia, septic shock, and urosepsis (0.2% each). Additional fatal adverse reactions were reported in 2 patients in the post-surgery phase before adjuvant treatment started, including pneumonia and sepsis (1 patient each).

Adverse reactions leading to discontinuation of PADCEV in the neoadjuvant phase occurred in 21% of patients. The most common adverse reactions (≥1%) leading to discontinuation of PADCEV were peripheral neuropathy (5%) and rash (3.5%).

Adverse reactions leading to dose interruption of PADCEV in the neoadjuvant phase occurred in 35% of patients. The most common adverse reactions (≥2%) leading to dose interruption of PADCEV were rash (10%), increased alanine aminotransferase (4%), neutropenia (3.7%), and hyperglycemia (3%).

Adverse reactions leading to dose reduction of PADCEV in the neoadjuvant phase occurred in 15% of patients. The most common adverse reactions (≥1%) leading to dose reduction of PADCEV were rash (9%) and pruritus (2%).

Of the 403 patients in the PADCEV in combination with intravenous pembrolizumab arm who received neoadjuvant treatment, 13 (3.2%) patients did not receive surgery due to adverse reactions. The adverse reactions that led to cancellation of surgery were multiple organ dysfunction syndrome (0.5%) and adenocarcinoma of colon, COVID-19 pneumonia, cardiac arrest, chronic obstructive pulmonary disease, coronary artery disease, glomerulonephritis, immune-mediated lung disease, myocarditis, pneumonia, pneumonitis, and urosepsis (0.2% each).

Of the 351 patients who received neoadjuvant treatment with PADCEV in combination with intravenous pembrolizumab and underwent RC, 26 (7%) patients experienced delay of surgery (defined as time from last neoadjuvant treatment to surgery exceeding 8 weeks) due to adverse reactions.

Adjuvant Phase of EV-304

Patients who did not proceed to surgery were ineligible for adjuvant treatment. Of the 351 patients who underwent surgery, 225 patients received adjuvant treatment with PADCEV with or without intravenous pembrolizumab. Of the 126 patients who did not receive adjuvant PADCEV, discontinuation of PADCEV prior to the adjuvant phase was due to an adverse event in 65 patients.

In the adjuvant phase, serious adverse reactions occurred in 36% of patients receiving PADCEV. The most common serious adverse reactions (≥1.5%) in the adjuvant phase in patients who received adjuvant PADCEV included urinary tract infection (8%), sepsis (2.2%), and diarrhea, hyperglycemia, pneumonitis/ILD, and urosepsis (1.8% each). Fatal adverse reactions in the adjuvant phase in patients who received adjuvant PADCEV occurred in 3.1% of patients and included cardiac arrest, death, duodenal ulcer perforation, acute pancreatitis, renal failure, small cell lung cancer, and toxic shock syndrome (0.4% each).

Adverse reactions leading to discontinuation of PADCEV in the adjuvant phase occurred in 16% of patients who received PADCEV in the adjuvant phase. The most common adverse reactions (≥1%) leading to discontinuation of PADCEV were rash (3.6%), peripheral neuropathy (1.8%), and urinary tract infection (1.3%).

Adverse reactions leading to dose interruption of PADCEV in the adjuvant phase occurred in 34% of patients who received PADCEV in the adjuvant phase. The most common adverse reactions (≥2%) leading to dose interruption of PADCEV were diarrhea and urinary tract infection (5% each), rash (4%), and COVID-19 (2.7%).

Adverse reactions leading to dose reduction of PADCEV in the adjuvant phase occurred in 5% of patients who received PADCEV in the adjuvant phase. The most common adverse reaction (>1%) resulting in dose reduction of PADCEV in the adjuvant phase included rash (1.3%).

Neoadjuvant and Adjuvant Treatment of Patients with MIBC Who Are Cisplatin-Ineligible

EV-303

The safety of PADCEV in combination with intravenous pembrolizumab as neoadjuvant treatment and continued after RC as adjuvant treatment was evaluated in an open-label, randomized, multicenter trial (EV-303) in patients with previously untreated MIBC who were ineligible for or declined cisplatin-based chemotherapy. Patients received PADCEV 1.25 mg/kg in combination with intravenous pembrolizumab (n=167) before and after RC with PLND or RC with PLND alone (n=159) [see Clinical Studies (14)].

For the 167 patients who received PADCEV in the neoadjuvant phase, the median duration of exposure to PADCEV was 1.6 months (range: 0.03 to 2.8 months) and the median number of cycles of PADCEV was 3 (range: 1, 3) in the neoadjuvant phase. Out of 100 patients who received adjuvant treatment in the PADCEV in combination arm, 92 patients received PADCEV. The median duration of exposure to PADCEV was 3.7 months (range: 0.03 to 7.6 months) and the median number of cycles of PADCEV was 6 (range: 1, 6) for patients who received PADCEV in the adjuvant phase. Across the combined neoadjuvant and adjuvant phases (n=167), the median number of cycles of PADCEV was 5 (range: 1, 9) out of a planned 9 cycles.

Table 7 summarizes the most common (≥20%) adverse reactions in EV-303.

Table 7. Adverse Reactions ≥20% (All Grades) in Patients Treated with PADCEV in Combination with Intravenous Pembrolizumab in EV-303
* Graded per NCI CTCAE v4.03. † Includes multiple terms.
Adverse Reaction	Perioperative PADCEV in combination with intravenous pembrolizumab n=167		RC with PLND alone n=159
Adverse Reaction	All Grades* %	Grade 3-4 %	All Grades* %	Grade 3-4 %
Skin and subcutaneous tissue disorders
Rash†	54	7	1.3	0
Pruritus	47	3	0	0
Alopecia	35	0.6	0	0
General disorders and administration site conditions
Fatigue†	47	4.2	6	0.6
Nervous system disorders
Peripheral neuropathy†	39	3	1.9	0
Dysgeusia†	35	0	0	0
Gastrointestinal disorders
Diarrhea†	34	5	3.1	1.3
Constipation	28	1.8	8	0
Nausea	26	1.2	8	0.6
Metabolism and nutrition disorders
Decreased appetite	28	0.6	1.9	0
Infections and infestations
Urinary tract infection	24	12	13	11
Eye disorders
Dry eye†	21	0	0	0
Investigations
Decreased weight	20	0	3.1	0

Clinically relevant adverse reactions (<20%) include dry skin (15%), hypothyroidism (14%), vomiting (9%), pneumonitis/ILD (4.2%), skin hyperpigmentation (3%), infusion site extravasation (1.2%), and myasthenia gravis and myositis (0.6% each).

Table 8. Selected Laboratory Abnormalities Reported in ≥20% (All Grades) of Patients Treated with PADCEV in Combination with Intravenous Pembrolizumab in EV-303
* The denominator used to calculate the rate of PADCEV in combination with intravenous pembrolizumab was 167 and the denominator used to calculate the rate for RC and PLND alone varied from 110 to 121 based on the number of patients with a baseline value and at least one post-treatment value. † Graded per NCI CTCAE v4.03.
Laboratory Abnormality*	Perioperative PADCEV in combination with intravenous pembrolizumab		RC with PLND alone
Laboratory Abnormality*	All Grades† %	Grade 3-4 %	All Grades† %	Grade 3-4 %
Chemistry
Increased glucose	72	12	24	1.7
Increased aspartate aminotransferase	55	6	11	1.8
Increased alanine aminotransferase	53	4.8	13	0.9
Increased creatinine	47	8	31	2.5
Decreased sodium	44	13	18	7
Increased potassium	39	7	20	6
Decreased phosphate	26	6	1.8	0
Hematology
Decreased hemoglobin	60	13	48	8
Decreased lymphocytes	40	8	17	1.7

Neoadjuvant Phase of EV-303

A total of 167 patients received at least one dose of PADCEV in combination with intravenous pembrolizumab as neoadjuvant treatment before receiving RC.

In the neoadjuvant phase, serious adverse reactions occurred in 27% of patients receiving PADCEV in combination with intravenous pembrolizumab. The most frequent (≥2%) serious adverse reactions were urinary tract infection (3.6%) and hematuria (2.4%). Fatal adverse reactions occurred in 1.2% of patients including myasthenia gravis and TEN (0.6% each). Additional fatal adverse reactions were reported in 2.7% of patients in the post-surgery phase before adjuvant treatment started, including sepsis and intestinal obstruction (1.4% each).

Adverse reactions leading to discontinuation of PADCEV in the neoadjuvant phase occurred in 22% of patients. The most common adverse reactions (≥1%) leading to discontinuation of PADCEV were rash (4.8%), peripheral neuropathy (2.4%), and diarrhea, dysgeusia, fatigue, pruritus, and TEN (1.2% each).

Adverse reactions leading to dose interruption of PADCEV in the neoadjuvant phase occurred in 29% of patients. The most common adverse reactions (≥2%) leading to dose interruption of PADCEV were rash (8%), neutropenia (3.6%), hyperglycemia (3%), and fatigue and peripheral neuropathy (2.4% each).

Adverse reactions leading to dose reduction of PADCEV in the neoadjuvant phase occurred in 13% of patients. The most common adverse reactions (≥1%) leading to dose reduction of PADCEV were rash (4.8%), pruritus (1.8%), and peripheral neuropathy, increase alanine aminotransferase, increased aspartate aminotransferase, decreased appetite, fatigue, neutropenia, and decreased weight (1.2% each).

Of the 167 patients in the PADCEV in combination with intravenous pembrolizumab arm who received neoadjuvant treatment, 7 (4.2%) patients did not receive surgery due to adverse reactions. The most common adverse reactions that led to cancellation of surgery were acute myocardial infarction, bile duct cancer, colon cancer, respiratory distress, urinary tract infection and the deaths due to myasthenia gravis and TEN (0.6% each).

Of the 146 patients who received neoadjuvant treatment with PADCEV in combination with intravenous pembrolizumab and underwent RC, 6 (4.1%) patients experienced delay of surgery (defined as time from last neoadjuvant treatment to surgery exceeding 8 weeks) due to adverse reactions.

Adjuvant Phase of EV-303

Patients who did not proceed to surgery were ineligible for adjuvant treatment. Of the 146 patients who underwent surgery, 92 patients received adjuvant treatment with PADCEV with or without intravenous pembrolizumab. Of the 54 patients who did not receive adjuvant PADCEV, discontinuation of PADCEV prior to the adjuvant phase was due to an adverse event in 27 patients.

In the adjuvant phase, serious adverse reactions occurred in 43% of patients receiving PADCEV. The most frequent (≥2%) serious adverse reactions were urinary tract infection (8%), acute kidney injury, pyelonephritis, and urosepsis (4.3% each), and hypokalemia, intestinal obstruction, and sepsis (2.2% each). Fatal adverse reactions occurred in 8% of patients who received PADCEV in the adjuvant phase, including urosepsis, hemorrhage intracranial, death, myocardial infarction, multiple organ dysfunction syndrome, and pneumonia pseudomonal (1.1% each).

Adverse reactions leading to discontinuation of PADCEV in the adjuvant phase occurred in 28% of patients who received PADCEV in the adjuvant phase. The most common adverse reactions (≥2%) leading to discontinuation of PADCEV were peripheral neuropathy (5%) and rash (4.3%).

Adverse reactions leading to dose interruption of PADCEV in the adjuvant phase occurred in 39% of patients who received PADCEV in the adjuvant phase. The most common adverse reactions (≥2%) leading to dose interruption of PADCEV were rash (7%), diarrhea and urinary tract infection (5% each), fatigue (4.3%), pruritus (3.3%), and peripheral neuropathy and pyelonephritis (2.2% each).

Adverse reactions leading to dose reduction of PADCEV in the adjuvant phase occurred in 8% of patients who received PADCEV in the adjuvant phase. The most common adverse reaction (≥2%) leading to dose reduction of PADCEV was weight decreased (2.2%).

Previously Untreated LA/mUC

EV-302

The safety of PADCEV in combination with intravenous pembrolizumab was evaluated in an open-label, randomized, multicenter trial (EV-302) in patients with la/mUC. Patients received either PADCEV 1.25 mg/kg and pembrolizumab (n=440) or gemcitabine and platinum chemotherapy (either cisplatin or carboplatin) (n=433). Among patients who received PADCEV and pembrolizumab, the median duration of exposure for PADCEV was 7 months (range: 0.3 to 31.9 months).

Serious adverse reactions occurred in 50% of patients treated with PADCEV in combination with intravenous pembrolizumab. The most common serious adverse reactions (≥2%) were rash (6%), acute kidney injury (5%), pneumonitis/ILD (4.5%), urinary tract infection (3.6%), diarrhea (3.2%), pneumonia (2.3%), pyrexia (2%), and hyperglycemia (2%).

Fatal adverse reactions occurred in 3.9% of patients treated with PADCEV in combination with intravenous pembrolizumab including acute respiratory failure (0.7%), pneumonia (0.5%), and pneumonitis/ILD (0.2%).

Adverse reactions leading to discontinuation of PADCEV occurred in 35% of patients. The most common adverse reactions (≥2%) leading to discontinuation of PADCEV were peripheral neuropathy (15%), rash (4.1%), and pneumonitis/ILD (2.3%).

Adverse reactions leading to dose interruption of PADCEV occurred in 73% of patients. The most common adverse reactions (≥2%) leading to dose interruption of PADCEV were peripheral neuropathy (22%), rash (16%), COVID-19 (10%), diarrhea (5%), pneumonitis/ILD (4.8%), fatigue (3.9%), hyperglycemia (3.6%), increased alanine aminotransferase (3%), and pruritus (2.5%).

Adverse reactions leading to dose reduction of PADCEV occurred in 42% of patients. The most common adverse reactions (≥2%) leading to dose reduction of PADCEV were rash (16%), peripheral neuropathy (13%), and fatigue (2.7%).

Table 9 summarizes the most common (≥15%) adverse reactions in EV-302.

Table 9. Adverse Reactions ≥15% (All Grades) in Patients Treated with PADCEV in Combination with Intravenous Pembrolizumab in EV-302
* Graded per NCI CTCAE v4.03. † Includes multiple terms.
Adverse Reaction	PADCEV in combination with intravenous pembrolizumab n=440		Chemotherapy n=433
Adverse Reaction	All Grades* %	Grade 3-4 %	All Grades* %	Grade 3-4 %
Skin and subcutaneous tissue disorders
Rash†	68	15	15	0
Pruritus	41	1.1	7	0
Alopecia	35	0.5	8	0.2
Dry skin	17	0.2	1	0
General disorders and administration site conditions
Fatigue†	51	6	57	7
Pyrexia	18	0.7	16	1.2
Nervous system disorders
Peripheral neuropathy†	67	8	14	0
Dysgeusia	21	0	9	0
Metabolism and nutrition disorders
Decreased appetite	33	1.8	26	1.8
Gastrointestinal disorders
Diarrhea	38	4.5	16	1.4
Nausea	26	1.6	41	2.8
Constipation	26	0	34	0.7
Investigations
Decreased weight	33	3.6	9	0.2
Eye disorders
Dry eye†	24	0	2.1	0
Infections and infestations
Urinary tract infection	21	5	19	8

Clinically relevant adverse reactions (<15%) include vomiting (12%), pneumonitis/ILD and hypothyroidism (10% each), blurred vision and skin hyperpigmentation (6% each), infusion site extravasation (1.8%), and myositis (0.5%).

Table 10. Selected Laboratory Abnormalities Reported in ≥15% (All Grades) of Patients Treated with PADCEV in Combination with Intravenous Pembrolizumab in EV-302
* The denominator used to calculate the rate varied from 407 to 439 based on the number of patients with a baseline value and at least one post-treatment value. † Graded per NCI CTCAE v4.03.
Laboratory Abnormality*	PADCEV in combination with intravenous pembrolizumab		Chemotherapy
Laboratory Abnormality*	All Grades† %	Grade 3-4 %	All Grades† %	Grade 3-4 %
Chemistry
Increased aspartate aminotransferase	75	5	39	3
Increased creatinine	71	3	68	3
Increased glucose	66	14	54	5
Increased alanine aminotransferase	59	5	49	3
Decreased sodium	46	13	47	13
Decreased phosphate	44	9	36	9
Decreased albumin	39	2	35	0.5
Decreased potassium	26	5	16	3
Increased potassium	24	1	36	4
Increased calcium	21	1	14	0.2
Hematology
Decreased lymphocytes	58	15	59	17
Decreased hemoglobin	53	7	89	33
Decreased neutrophils	30	9	80	50

Previously Untreated Patients with LA/mUC Who Are Cisplatin-Ineligible

EV-103

The safety of PADCEV was evaluated in combination with intravenous pembrolizumab in a multi cohort trial (EV-103) in 121 patients with la/mUC who were not eligible for cisplatin-containing chemotherapy and received at least one dose of PADCEV 1.25 mg/kg and pembrolizumab [see Clinical Studies (14)]. The median duration of exposure to PADCEV was 7 months (range: 0.6 to 33 months).

Serious adverse reactions occurred in 50% of patients treated with PADCEV in combination with intravenous pembrolizumab. The most common serious adverse reactions (≥2%) were acute kidney injury (7%), urinary tract infection (7%), urosepsis (5%), sepsis (3.3%), pneumonia (3.3%), hematuria (3.3%), pneumonitis/ILD (3.3%), urinary retention (2.5%), diarrhea (2.5%), myasthenia gravis (2.5%), myositis (2.5%), anemia (2.5%), and hypotension (2.5%).

Fatal adverse reactions occurred in 5% of patients treated with PADCEV in combination with intravenous pembrolizumab including sepsis (1.6%), bullous dermatitis (0.8%), myasthenia gravis (0.8%), and pneumonitis/ILD (0.8%).

Adverse reactions leading to discontinuation of PADCEV occurred in 36% of patients. The most common adverse reactions (≥2%) leading to discontinuation of PADCEV were peripheral neuropathy (20%) and rash (6%).

Adverse reactions leading to dose interruption of PADCEV occurred in 69% of patients. The most common adverse reactions (≥2%) leading to dose interruption of PADCEV were peripheral neuropathy (18%), rash (12%), increased lipase (6%), pneumonitis/ILD (6%), diarrhea (4.1%), acute kidney injury (3.3%), increased alanine aminotransferase (3.3%), fatigue (3.3%), neutropenia (3.3%), urinary tract infection (3.3%), increased amylase (2.5%), anemia (2.5%), COVID-19 (2.5%), hyperglycemia (2.5%), and hypotension (2.5%).

Adverse reactions leading to dose reduction of PADCEV occurred in 45% of patients. The most common adverse reactions (≥2%) leading to dose reduction of PADCEV were peripheral neuropathy (17%), rash (12%), fatigue (5%), neutropenia (5%), and diarrhea (4.1%).

Table 11 summarizes the most common (≥20%) adverse reactions in EV-103.

Table 11. Adverse Reactions ≥20% (All Grades) in Patients Treated with PADCEV in Combination with Intravenous Pembrolizumab in EV-103
* Graded per NCI CTCAE v4.03. † Includes multiple terms.
Adverse Reaction	PADCEV in combination with intravenous pembrolizumab n=121
Adverse Reaction	All Grades* %	Grade 3-4 %
Skin and subcutaneous tissue disorders
Rash†	71	21
Alopecia	52	0
Pruritus	40	3.3
Dry skin	21	0.8
Nervous system disorders
Peripheral neuropathy†	65	3.3
Dysgeusia	35	0
Dizziness	23	0
General disorders and administration site conditions
Fatigue	60	11
Peripheral edema	26	0
Investigations
Decreased weight	48	5
Gastrointestinal disorders
Diarrhea	45	7
Nausea	36	0.8
Constipation	27	0
Metabolism and nutrition disorders
Decreased appetite	38	0.8
Infections and infestations
Urinary tract infection	30	12
Eye disorders
Dry eye	25	0
Musculoskeletal and connective tissue disorders
Arthralgia	23	1.7

Clinically relevant adverse reactions (<20%) include vomiting (20%), pyrexia (18%), hypothyroidism (11%), pneumonitis/ILD (10%), skin hyperpigmentation (8%), myasthenia gravis (2.5%), myositis (3.3%), and infusion site extravasation (0.8%).

Table 12. Selected Laboratory Abnormalities ≥20% (All Grades) in Patients Treated with PADCEV in Combination with Intravenous Pembrolizumab in EV-103
Laboratory Abnormality*	PADCEV in combination with intravenous pembrolizumab
Laboratory Abnormality*	All Grades† %	Grade 3-4 %
* The denominator used to calculate the rate varied from 114 to 121 based on the number of patients with a baseline value and at least one post-treatment value. † Graded per NCI CTCAE v4.03.
Chemistry
Increased glucose	74	13
Increased aspartate aminotransferase	73	9
Increased creatinine	69	3.3
Decreased sodium	60	19
Increased alanine aminotransferase	60	7
Increased lipase	59	32
Decreased albumin	59	4.2
Decreased phosphate	51	15
Decreased potassium	35	8
Increased potassium	27	1.7
Increased calcium	27	4.2
Hematology
Decreased hemoglobin	69	15
Decreased lymphocytes	64	17
Decreased neutrophils	32	12

Previously Treated LA/mUC

EV-301

The safety of PADCEV was evaluated as a single agent in EV-301 in patients with la/mUC (n=296) who received at least one dose of PADCEV 1.25 mg/kg and who were previously treated with a PD-1 or PD-L1 inhibitor and a platinum-based chemotherapy [see Clinical Studies (14)]. Routine ophthalmologic exams were not conducted in EV-301. The median duration of exposure to PADCEV was 5 months (range: 0.5 to 19 months).

Serious adverse reactions occurred in 47% of patients treated with PADCEV. The most common serious adverse reactions (≥2%) were urinary tract infection, acute kidney injury (7% each), and pneumonia (5%). Fatal adverse reactions occurred in 3% of patients, including multiorgan dysfunction (1%), hepatic dysfunction, septic shock, hyperglycemia, pneumonitis/ILD, and pelvic abscess (0.3% each).

Adverse reactions leading to discontinuation occurred in 17% of patients; the most common adverse reactions (≥2%) leading to discontinuation were peripheral neuropathy (5%) and rash (4%).

Adverse reactions leading to dose interruption occurred in 61% of patients; the most common adverse reactions (≥4%) leading to dose interruption were peripheral neuropathy (23%), rash (11%), and fatigue (9%).

Adverse reactions leading to dose reduction occurred in 34% of patients; the most common adverse reactions (≥2%) leading to dose reduction were peripheral neuropathy (10%), rash (8%), decreased appetite (3%), and fatigue (3%).

Table 13 summarizes the most common (≥15%) adverse reactions in EV-301.

Table 13. Adverse Reactions (≥15%) in Patients Treated with PADCEV in EV-301
* Graded per NCI CTCAE v4.03. † Includes multiple terms.
Adverse Reaction	PADCEV n=296		Chemotherapy n=291
Adverse Reaction	All Grades* %	Grade 3-4 %	All Grades* %	Grade 3-4 %
Skin and subcutaneous tissue disorders
Rash†	54	14	20	0.3
Alopecia	47	0	38	0
Pruritus	34	2	7	0
Dry skin	17	0	4	0
General disorders and administration site conditions
Fatigue†	50	9	40	7
Pyrexia†	22	2	14	0
Nervous system disorders
Peripheral neuropathy†	50	5	34	3
Dysgeusia†	26	0	8	0
Metabolism and nutrition disorders
Decreased appetite	41	5	27	2
Gastrointestinal disorders
Diarrhea†	35	4	23	2
Nausea	30	1	25	2
Constipation	28	1	25	2
Abdominal Pain†	20	1	14	3
Musculoskeletal and connective tissue disorders
Musculoskeletal Pain†	25	2	35	5
Eye Disorders
Dry eye†	24	0.7	6	0.3
Infections and infestations
Urinary Tract Infection†	17	6	13	3
Vascular disorders
Hemorrhage†	17	3	13	2
Investigations
Decreased weight	16	0.3	7	0

Clinically relevant adverse reactions (<15%) include vomiting (14%), increased aspartate aminotransferase (12%), hyperglycemia (10%), increased alanine aminotransferase (9%), skin hyperpigmentation (8%), pneumonitis/ILD (3%), and infusion site extravasation (0.7%).

Table 14. Selected Laboratory Abnormalities Reported in ≥15% (Grades 2-4) or ≥5% (Grade 3-4) of Patients Treated with PADCEV in EV-301
* The denominator used to calculate the rate varied from 262 to 287 based on the number of patients with a baseline value and at least one post-treatment value. † Graded per NCI CTCAE v4.03.
Laboratory Abnormality*	PADCEV		Chemotherapy
Laboratory Abnormality*	Grades 2-4† %	Grade 3-4 %	Grades 2-4† %	Grade 3-4 %
Hematology
Decreased lymphocytes	41	14	34	18
Decreased hemoglobin	28	4	42	14
Decreased neutrophils	27	12	25	17
Chemistry
Decreased phosphate	39	8	24	6
Increased glucose (non‑fasting)	33	9	27	6
Increased creatinine	18	2	13	0
Decreased potassium	16	2	7	3
Increased lipase	13	8	7	4
Decreased sodium	8	8	5	5

EV-201, Cohort 1

The safety of PADCEV was evaluated as a single agent in EV-201, Cohort 1 in patients (n=125) with la/mUC who had received prior treatment with a PD-1 or PD-L1 inhibitor and platinum-based chemotherapy [see Clinical Studies (14)]. Patients received PADCEV 1.25 mg/kg on Days 1, 8, and 15 of a 28-day cycle until disease progression or unacceptable toxicity. The median duration of exposure to PADCEV was 4.6 months (range: 0.5 to 15.6 months).

Serious adverse reactions occurred in 46% of patients treated with PADCEV. The most common serious adverse reactions (≥3%) were urinary tract infection (6%), cellulitis (5%), febrile neutropenia (4%), diarrhea (4%), sepsis (3%), acute kidney injury (3%), dyspnea (3%), and rash (3%). Fatal adverse reactions occurred in 3.2% of patients, including acute respiratory failure, aspiration pneumonia, cardiac disorder, sepsis, and pneumonitis/ILD (each 0.8%).

Adverse reactions leading to discontinuation occurred in 16% of patients; the most common adverse reaction leading to discontinuation was peripheral neuropathy (6%).

Adverse reactions leading to dose interruption occurred in 64% of patients; the most common adverse reactions leading to dose interruption were peripheral neuropathy (18%), rash (9%), and fatigue (6%).

Adverse reactions leading to dose reduction occurred in 34% of patients; the most common adverse reactions leading to dose reduction were peripheral neuropathy (12%), rash (6%), and fatigue (4%).

Table 15 summarizes the All Grades and Grades 3-4 adverse reactions reported in patients in EV-201, Cohort 1.

Table 15. Adverse Reactions Reported in ≥15% (All Grades) or ≥5% (Grade 3-4) of Patients Treated with PADCEV in EV-201 Cohort 1
Adverse Reaction	PADCEV n=125
Adverse Reaction	All Grades* %	Grade 3-4 %
* Graded per NCI CTCAE v4.03. † Includes multiple terms.
General disorders and administration site conditions
Fatigue†	56	6
Nervous system disorders
Peripheral neuropathy†	56	4
Dysgeusia	42	0
Metabolism and nutrition disorders
Decreased appetite	52	2
Skin and subcutaneous tissue disorders
Rash†	52	13
Alopecia	50	0
Dry skin	26	0
Pruritus†	26	2
Gastrointestinal disorders
Nausea	45	3
Diarrhea†	42	6
Vomiting	18	2
Eye disorders
Dry eye†	40	0

Clinically relevant adverse reactions (<15%) include skin hyperpigmentation (14%), herpes zoster (3%), pneumonitis/ILD (2%), and infusion site extravasation (2%).

Table 16. Selected Laboratory Abnormalities Reported in ≥15% (Grades 2-4) or ≥5% (Grade 3-4) of Patients Treated with PADCEV in EV-201, Cohort 1
Laboratory Abnormality*	PADCEV
Laboratory Abnormality*	Grades 2-4† %	Grade 3-4 %
* Denominator for each laboratory parameter is based on the number of patients with a baseline and post-treatment laboratory value available for 121 or 122 patients. † Graded per NCI CTCAE v4.03. ‡ Includes Grade 1 (potassium 3.0-3.5 mmol/L) – Grade 4.
Hematology
Decreased hemoglobin	34	10
Decreased lymphocytes	32	10
Decreased neutrophils	14	5
Chemistry
Decreased phosphate	34	10
Increased glucose (non-fasting)	27	8
Increased creatinine	20	2
Decreased potassium	19‡	1
Increased lipase	14	9
Decreased sodium	8	8
Increased urate	7	7

EV-201, Cohort 2

The safety of PADCEV was evaluated as a single agent in EV-201, Cohort 2 in patients with la/mUC (n=89) who received at least one dose of PADCEV 1.25 mg/kg and had prior treatment with a PD-1 or PD-L1 inhibitor and were not eligible for cisplatin-based chemotherapy. The median duration of exposure was 5.98 months (range: 0.3 to 24.6 months).

Serious adverse reactions occurred in 39% of patients treated with PADCEV. The most common serious adverse reactions (≥3%) were pneumonia, sepsis, and diarrhea (5% each). Fatal adverse reactions occurred in 8% of patients, including acute kidney injury (2.2%), metabolic acidosis, sepsis, multiorgan dysfunction, pneumonia, and pneumonitis/ILD (1.1% each).

Adverse reactions leading to discontinuation occurred in 20% of patients; the most common adverse reaction (≥2%) leading to discontinuation was peripheral neuropathy (7%).

Adverse reactions leading to dose interruption occurred in 60% of patients; the most common adverse reactions (≥3%) leading to dose interruption were peripheral neuropathy (19%), rash (9%), fatigue (8%), diarrhea (5%), increased aspartate aminotransferase (3%), and hyperglycemia (3%).

Adverse reactions leading to dose reduction occurred in 49% of patients; the most common adverse reactions (≥3%) leading to dose reduction were peripheral neuropathy (19%), rash (11%), and fatigue (7%).

Table 17 summarizes the All Grades and Grades 3-4 adverse reactions reported in patients in EV-201, Cohort 2.

Table 17. Adverse Reactions ≥15% (All Grades) or ≥5% (Grades 3-4) in Patients Treated with PADCEV in EV‑201, Cohort 2
Adverse Reaction	PADCEV n=89
Adverse Reaction	All Grades* (%)	Grades 3-4 (%)
* Graded per NCI CTCAE v4.03. † Includes multiple terms.
Skin and subcutaneous tissue disorders
Rash†	66	17
Alopecia	53	0
Pruritus	35	3
Dry skin	19	1
Nervous system disorders
Peripheral neuropathy†	58	8
Dysgeusia†	29	0
General disorders and administration site conditions
Fatigue†	48	11
Metabolism and nutrition disorders
Decreased appetite	40	6
Hyperglycemia	16	9
Gastrointestinal disorders
Diarrhea†	36	8
Nausea	30	1
Investigations
Decreased weight	35	1
Eye disorders
Dry eye†	30	0

Clinically relevant adverse reactions (<15%) include vomiting (13%), increased aspartate aminotransferase (12%), increased lipase (11%), increased alanine aminotransferase (10%), skin hyperpigmentation (4%), pneumonitis/ILD (4%), and infusion site extravasation (1%).

Table 18. Selected Laboratory Abnormalities Reported in ≥15% (Grades 2-4) or ≥5% (Grades 3-4) of Patients Treated with PADCEV in EV-201, Cohort 2
Laboratory Abnormality*	PADCEV n=88*
Laboratory Abnormality*	Grades 2-4† %	Grade 3-4 %
* Based on the number of patients with a baseline value and at least one post-treatment value. † Graded per NCI CTCAE v4.03.
Hematology
Decreased lymphocytes	43	15
Decreased hemoglobin	34	5
Decreased neutrophils	20	9
Chemistry
Increased glucose (non-fasting)	36	13
Decreased phosphate	25	7
Increased creatinine	23	3
Increased lipase	18	11
Increased urate	9	9
Increased potassium	8	6
Decreased sodium	7	7

6.2 Post Marketing Experience

The following adverse reactions have been identified during post-approval use of PADCEV. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Skin and subcutaneous tissue disorders: Epidermal necrosis, SJS, and TEN [see Warnings and Precautions (5.1)].

Medication Guide

MEDICATION GUIDE

PATIENT INFORMATION PADCEV® (PAD-sev) (enfortumab vedotin-ejfv) for injection
If your healthcare provider prescribes PADCEV in combination with the medicines pembrolizumab or pembrolizumab and berahyaluronidase alfa-pmph, also read the Medication Guide that comes with these medicines for additional important information.
What is the most important information I should know about PADCEV? PADCEV may cause serious side effects, including: Skin reactions. Skin reactions including severe skin reactions have happened in people treated with PADCEV and may be more common when PADCEV is given with pembrolizumab. In some cases, these severe skin reactions have caused death. Most severe skin reactions occurred during the first cycle of treatment but may happen later. Your healthcare provider will monitor you, may stop your treatment with PADCEV completely or for a period of time (temporarily), may change your dose, and may prescribe medicines if you get skin reactions. Tell your healthcare provider right away if you develop any of these signs of a new or worsening skin reaction:
• target lesions (skin reactions that look like rings) • rash or itching that continues to get worse • blistering or peeling of the skin		• painful sores or ulcers in mouth or nose, throat, or genital area • fever or flu-like symptoms • swollen lymph nodes
See “What are the possible side effects of PADCEV?” for more information about side effects.
What is PADCEV? PADCEV is a prescription medicine used to treat adults with bladder cancer and cancers of the urinary tract (renal pelvis, ureter, or urethra). • PADCEV may be used with pembrolizumab or pembrolizumab and berahyaluronidase alfa-pmph before and after the surgical removal of your bladder when your bladder cancer has spread into the muscle layer of the bladder (muscle invasive bladder cancer [MIBC]) but not to other parts of the body. • PADCEV may be used with pembrolizumab or pembrolizumab and berahyaluronidase alfa-pmph when your bladder or urinary tract cancer has spread or cannot be removed by surgery (locally advanced or metastatic). • PADCEV may be used alone when your bladder or urinary tract cancer has spread or cannot be removed by surgery (locally advanced or metastatic) if you: o have received PD-1 or PD-L1 immunotherapy medicine and chemotherapy that contains platinum, or o are not able to receive a chemotherapy that contains cisplatin and you have received 1 or more prior therapies. It is not known if PADCEV is safe and effective in children.
Before receiving PADCEV, tell your healthcare provider about all of your medical conditions, including if you: • are currently experiencing numbness or tingling in your hands or feet • have a history of high blood sugar or diabetes • have liver problems • are pregnant or plan to become pregnant. PADCEV can harm your unborn baby. Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with PADCEV. Females who are able to become pregnant: o Your healthcare provider should do a pregnancy test before you start treatment with PADCEV. o You should use an effective method of birth control during your treatment and for at least 2 months after the last dose of PADCEV. Males with a female sexual partner who is able to become pregnant: o If your female partner is pregnant, PADCEV can harm the unborn baby. o You should use an effective method of birth control during your treatment and for at least 4 months after the last dose of PADCEV. • are breastfeeding or plan to breastfeed. It is not known if PADCEV passes into your breast milk. Do not breastfeed during treatment and for 3 weeks after the last dose of PADCEV. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Taking PADCEV with certain other medicines may cause side effects.
How will I receive PADCEV? • PADCEV will be given to you by intravenous (IV) infusion into your vein over 30 minutes. • PADCEV is given over periods of time called “cycles”. • If you receive PADCEV with pembrolizumab or pembrolizumab and berahyaluronidase alfa-pmph: o Each cycle is 21 days. o You will receive PADCEV on days 1 and 8 of every cycle. • If you receive PADCEV alone: o Each PADCEV cycle is 28 days. o You will receive PADCEV on days 1, 8, and 15 of every cycle. • Your healthcare provider will decide how many treatment cycles you need. • Your healthcare provider may do blood tests regularly during treatment with PADCEV.
What are the possible side effects of PADCEV? PADCEV may cause serious side effects, including: • See “What is the most important information I should know about PADCEV?” • High blood sugar (hyperglycemia). An increase in blood sugar is common during treatment with PADCEV. Severe high blood sugar, a serious condition called diabetic ketoacidosis (DKA), and death have happened in people with and without diabetes, treated with PADCEV. Tell your healthcare provider right away if you get any symptoms of high blood sugar, including:
	o frequent urination o increased thirst o blurred vision o confusion o it becomes harder to control your blood sugar o drowsiness o loss of appetite o fruity smell on your breath o nausea, vomiting, or stomach pain
• Lung problems. PADCEV may cause severe or life-threatening inflammation of the lungs that can lead to death. These severe problems may happen more often when PADCEV is given in combination with pembrolizumab. Tell your healthcare provider right away if you get new or worsening symptoms, including trouble breathing, shortness of breath, or cough. • Nerve problems. Nerve problems called peripheral neuropathy are common during treatment with PADCEV and can also sometimes be severe. Nerve problems may happen more often when PADCEV is given in combination with pembrolizumab. Tell your healthcare provider right away if you get new or worsening numbness or tingling in your hands or feet or muscle weakness. • Eye problems. Certain eye problems are common during treatment with PADCEV. Tell your healthcare provider right away if you get dry eyes, increased tearing, blurred vision, or any vision changes. You may use artificial tear substitutes to help prevent or treat dry eyes. • Leakage of PADCEV out of your vein into the tissues around your infusion site (extravasation). If PADCEV leaks from the injection site or the vein into the nearby skin and tissues, it could cause an infusion site reaction. These reactions can happen right after you receive an infusion, but sometimes may happen days after your infusion. Tell your healthcare provider or get medical help right away if you notice any redness, swelling, itching, blister, peeling skin, or discomfort at the infusion site.
Your healthcare provider may decrease your dose of PADCEV, or temporarily or completely stop your treatment with PADCEV if you get severe side effects. The most common side effects of PADCEV when used in combination with pembrolizumab include:
• changes in liver function and kidney function tests • rash. See “What is the most important information I should know about PADCEV?” • increased sugar (glucose) in the blood. See “High blood sugar (hyperglycemia)” above. • numbness or tingling in your hands or feet. See “Nerve problems” above.		• increased lipase (a test done to check your pancreas) • decreased white blood cell, red blood cell, and platelet counts • tiredness • decreased sodium, phosphate, and protein (albumin) in the blood • itching • diarrhea • hair loss	• decreased weight • decreased appetite • increased uric acid in the blood • increased or decreased potassium • dry eye. See “Eye problems” above. • nausea • constipation • change in sense of taste • urinary tract infection
The most common side effects of PADCEV when used alone include:
• increased sugar (glucose) in the blood. See “High blood sugar (hyperglycemia)” above. • changes in liver and kidney function tests • decreased white blood cell, red blood cell, and platelet counts • rash. See “What is the most important information I should know about PADCEV?” • tiredness		• numbness or tingling in your hands or feet. See “Nerve problems” above. • decreased protein (albumin), sodium, and phosphate in the blood • hair loss • decreased appetite • diarrhea • nausea • itching	• increased uric acid in the blood • dry eye. See “Eye problems” above. • change in sense of taste • constipation • increased lipase (a blood test done to check your pancreas) • decreased weight • stomach (abdominal) pain • dry skin
PADCEV may cause fertility problems in females and males, which may affect the ability to have children. Talk to your healthcare provider if you have concerns about fertility. These are not all of the possible side effects of PADCEV. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
General information about the safe and effective use of PADCEV. Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. You can ask your pharmacist or healthcare provider for information about PADCEV that is written for healthcare professionals.
What are the ingredients in PADCEV? Active ingredient: enfortumab vedotin-ejfv Inactive ingredients: histidine, histidine hydrochloride monohydrate, polysorbate 20, and trehalose dihydrate. Manufactured and Marketed by: Astellas Pharma US, Inc., Northbrook, Illinois 60062 Distributed and Marketed by: Seagen Inc., Bothell, WA 98021 U.S. License 2124 PADCEV is a registered trademark jointly owned by Agensys, Inc. and Seagen Inc. ©2026 Agensys, Inc. and Seagen Inc. For more information, go to www.padcev.com or call 1-888-472-3238 10194-EV-US

: This Patient Information has been approved by the U.S. Food and Drug Administration. Revised: 07/2026

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