Recognizing Appropriate Patients for an Antibody-Drug Conjugate: Case Studies in Bladder Cancer

Sponsored Content by Astellas Pharma US, Inc. and Seagen Inc.

Nataliya Mar, MD

Locally advanced or metastatic urothelial carcinoma (la/mUC) is a form of bladder cancer that is typically associated with poor survival and high healthcare costs.¹ Chemotherapy regimens that contain cisplatin are the current standard of care in the first-line treatment setting for patients with la/mUC.^2,3 Carboplatin is also an option for patients not eligible for cisplatin-containing chemotherapy. In addition, certain PD-(L)1 inhibitors are considered treatment options in patients who are not eligible for any platinum-containing chemotherapy. In the second- and third-line settings, treatments may include checkpoint inhibitors and platinum-containing chemotherapy as well.

Both carboplatin and cisplatin-containing chemotherapies are platinum-based chemotherapies, which can be difficult for some patients to tolerate.⁴ For patients with la/mUC who are ineligible for cisplatin-containing chemotherapy and were previously treated with one or more prior lines of therapy, and for those who previously received platinum-containing chemotherapy and a PD-(L)1 inhibitor, an antibody-drug conjugate (ADC) may be considered.⁵

ADCs are a therapeutic modality composed of a monoclonal antibody that binds to a specific antigen, a cytotoxic payload and a linker designed to deliver and release cytotoxic agents at the target site.^6,7 PADCEV^® (enfortumab vedotin-ejfv) is an ADC directed against Nectin-4, a cell surface protein that is expressed on certain urothelial cancer cells.^5,8 PADCEV was granted accelerated approval by the U.S. Food and Drug Administration (FDA) in 2019, followed by regular approval in 2021, for patients with la/mUC who have previously received therapy with a PD-1/L1 inhibitor and platinum-containing chemotherapy, as well as those who are ineligible for cisplatin-based chemotherapy and have received one or more prior lines of therapy.^5,9

BOXED WARNING: SERIOUS SKIN REACTIONS. PADCEV can cause severe and fatal cutaneous adverse reactions including Stevens-Johnson syndrome (SJS) and Toxic Epidermal Necrolysis (TEN), which occurred predominantly during the first cycle of treatment, but may occur later. Closely monitor patients for skin reactions. Immediately withhold PADCEV and consider referral for specialized care for suspected SJS or TEN or severe skin reactions. Permanently discontinue PADCEV in patients with confirmed SJS or TEN; or Grade 4 or recurrent Grade 3 skin reactions.

PADCEV has WARNINGS AND PRECAUTIONS for hyperglycemia (withhold if blood glucose >250 mg/dL); pneumonitis/interstitial lung disease (ILD) (withhold for Grade 2 pneumonitis/ILD and consider dose reduction. Permanently discontinue PADCEV for Grade 3 or 4 pneumonitis/ILD); peripheral neuropathy (dose interrupt, reduce, or discontinue); ocular disorders (dose interrupt or reduce); infusion site extravasation (stop infusion); embryo-fetal toxicity (advise patient).

PADCEV was compared to chemotherapy in the EV-301 trial, an open-label, randomized, multicenter trial in adult patients (n=608) with la/mUC who were previously treated with platinum-based chemotherapy and a PD-1/L1 inhibitor. Patients who received PADCEV (n=301) in the trial lived a median of 3.9 months longer than those who received chemotherapy (n=307). Median overall survival was 12.9 months (95% CI: 10.6, 15.2) vs. 9.0 months (95% CI: 8.1, 10.7), respectively [Hazard Ratio=0.70 (95% Confidence Interval [CI]: 0.56, 0.89), p=0.0014].⁵

PADCEV was evaluated in Cohort 2 of the EV-201 trial, a single-arm, multicenter trial in patients (n=89) with la/mUC who had been previously treated with a PD-1/L1 inhibitor, had not received a platinum-containing chemotherapy in this setting, and were ineligible for cisplatin. Fifty-one percent of patients who received PADCEV had an objective response [95% CI: 39.8, 61.3] per blinded independent central review (complete response=22% and partial response=28%), with a median duration of response of 13.8 months [95% CI: 6.4, not estimable].⁵

The most common adverse reactions, including laboratory abnormalities (≥20%) for PADCEV monotherapy are: Rash, aspartate aminotransferase increased, glucose increased, creatinine increased, fatigue, peripheral neuropathy, lymphocytes decreased, alopecia, decreased appetite, hemoglobin decreased, diarrhea, sodium decreased, nausea, pruritus, phosphate decreased, dysgeusia, alanine aminotransferase increased, anemia, albumin decreased, neutrophils decreased, urate increased, lipase increased, platelets decreased, weight decreased and dry skin.⁵

The following hypothetical case studies illustrate the types of patients for whom PADCEV may be an appropriate next step in disease management.

Case Study 1

A 77-year-old man presented with progressively worsening urinary frequency, burning with urination and intermittent painless gross hematuria. A CT scan of his abdomen/pelvis showed a mass-like thickening of the left bladder wall, including the left ureterovesical junction.

A cystoscopy was performed, showing a large blood clot, but there was otherwise difficult visualization due to bleeding. Urine cytology from that procedure was positive for high-grade urothelial carcinoma. He then underwent a transurethral resection of bladder tumor (TURBT). Pathology showed high-grade urothelial carcinoma with invasion into the muscularis propria. A PET/CT scan showed a bladder mass with invasion into the prostate and rectum, as well as multiple enlarged common iliac lymph nodes. Next generation sequencing of the bladder tumor did not reveal any fibroblast growth factor receptor (FGFR) alterations.

Chemotherapy with cisplatin/gemcitabine was initiated. The patient completed five cycles of chemotherapy before discontinuing treatment due to worsening peripheral neuropathy. Subsequent restaging CT scan of the chest showed multiple new pulmonary nodules, which were too small to biopsy. Meanwhile, CT scan of his abdomen/pelvis showed an enlarging bladder mass as well as pelvic and retroperitoneal lymphadenopathy. He initiated immunotherapy with pembrolizumab and completed 18 cycles of treatment. Restaging body CT scans showed progression of pulmonary metastasis and enlargement of the bladder mass. Clinically, the patient developed recurrence of gross hematuria and worsening urinary frequency. While receiving pembrolizumab, his symptoms of peripheral neuropathy became mild. The patient discontinued pembrolizumab and was then initiated on PADCEV.

Case Study 2

A 58-year-old man presented to the emergency room with painless gross hematuria. An abdominopelvic CT scan revealed an 8-centimeter anterior bladder mass with possible extension into the extravesicular fat. A PET scan revealed a 1.0-centimeter FDG-avid external iliac lymph node, but no other suspicious lymphadenopathy or distant metastasis were noted. A TURBT was performed, and pathology demonstrated high-grade papillary urothelial carcinoma invasive into the muscularis propria.

Due to reduced renal function (CrCl=37), the patient was deemed ineligible for cisplatin-containing chemotherapy. He was initiated on immunotherapy with pembrolizumab. After completing eight cycles of treatment with pembrolizumab, he was found to have a rapidly enlarging neck mass, with associated pain, voice hoarseness, and dysphagia leading to weight loss. Restaging body CT scans showed enlarging neck and chest lymphadenopathy. Supraclavicular lymph node biopsy demonstrated metastatic urothelial carcinoma. Next-generation sequencing on this specimen did not reveal any FGFR alterations. The patient was then initiated on PADCEV.

Outlining the Role of ADCs in Advanced Disease

When evaluating treatment options for a patient with la/mUC who is ineligible for cisplatin-based chemotherapy and has received one or more prior treatments, or who had received previous treatment with a platinum-containing chemotherapy and a PD-(L)1 inhibitor, PADCEV may be considered.

It is important to remember that all patients are unique and may respond to PADCEV differently. However, physician awareness of this treatment option is important, and learning to recognize those who may be suitable for it could provide an important treatment alternative.

Please see Important Safety Information below and full Prescribing Information, including BOXED WARNING for Serious Skin Reactions for PADCEV.

BOXED WARNING: SERIOUS SKIN REACTIONS

• PADCEV can cause severe and fatal cutaneous adverse reactions including Stevens-Johnson syndrome (SJS) and Toxic Epidermal Necrolysis (TEN), which occurred predominantly during the first cycle of treatment, but may occur later.
• Closely monitor patients for skin reactions.
• Immediately withhold PADCEV and consider referral for specialized care for suspected SJS or TEN or severe skin reactions.
• Permanently discontinue PADCEV in patients with confirmed SJS or TEN; or Grade 4 or recurrent Grade 3 skin reactions.

Indication

PADCEV^®, as a single agent, is indicated for the treatment of adult patients with locally advanced or metastatic urothelial cancer (mUC) who:

• have previously received a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor and platinum-containing chemotherapy, or
• are ineligible for cisplatin-containing chemotherapy and have previously received one or more prior lines of therapy.

PADCEV, in combination with pembrolizumab, is indicated for the treatment of adult patients with locally advanced or metastatic urothelial cancer (mUC) who are not eligible for cisplatin-containing chemotherapy.

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

Important Safety Information
Warnings and Precautions

Skin reactions Severe cutaneous adverse reactions, including fatal cases of SJS or TEN occurred in patients treated with PADCEV. SJS and TEN occurred predominantly during the first cycle of treatment but may occur later. Skin reactions occurred in 56% (all grades) of the 753 patients treated with PADCEV as a single agent in clinical trials. Twenty-four percent (24%) of patients had maculo-papular rash and 33% had pruritus. Grade 3-4 skin reactions occurred in 12% of patients, including maculo-papular rash, erythematous rash, rash or drug eruption, symmetrical drug-related intertriginous and flexural exanthema (SDRIFE), bullous dermatitis, exfoliative dermatitis, and palmar-plantar erythrodysesthesia. The median time to onset of severe skin reactions was 0.7 months (range: 0.1 to 6 months). Among patients experiencing a skin reaction leading to dose interruption who then restarted PADCEV (n=59), 24% of patients restarting at the same dose and 16% of patients restarting at a reduced dose experienced recurrent severe skin reactions. Skin reactions led to discontinuation of PADCEV in 2.6% of patients.

When PADCEV was given in combination with pembrolizumab, the incidence of skin reactions, including severe events, occurred at a higher rate. Skin reactions occurred in 72% (all grades) of the 121 patients treated with PADCEV in combination with pembrolizumab in clinical trials. The majority of the skin reactions that occurred with combination therapy included maculo-papular rash, macular rash and papular rash. Grade 3-4 skin reactions occurred in 20% of patients (Grade 3: 19%, Grade 4: 0.8%), including maculo-papular rash, bullous dermatitis, dermatitis, exfoliative dermatitis, pemphigoid, rash, erythematous rash, macular rash, and papular rash. A fatal reaction of bullous dermatitis occurred in one patient (0.8%). The median time to onset of severe skin reactions was 2.6 months (range: 0.3 to 16 months). Skin reactions led to discontinuation of PADCEV in 6% of patients.

Monitor patients closely throughout treatment for skin reactions. Consider topical corticosteroids and antihistamines, as clinically indicated. For persistent or recurrent Grade 2 skin reactions, consider withholding PADCEV until Grade ≤1. Withhold PADCEV and refer for specialized care for suspected SJS, TEN or for Grade 3 skin reactions. Permanently discontinue PADCEV in patients with confirmed SJS or TEN; or Grade 4 or recurrent Grade 3 skin reactions.

Hyperglycemiaand diabetic ketoacidosis (DKA). Hyperglycemia and diabetic ketoacidosis (DKA), including fatal events, occurred in patients with and without pre-existing diabetes mellitus, treated with PADCEV. Patients with baseline hemoglobin A1C ≥8% were excluded from clinical trials. In clinical trials of PADCEV as a single agent, 14% of the 753 patients treated with PADCEV developed hyperglycemia; 7% of patients developed Grade 3-4 hyperglycemia. Fatal events of hyperglycemia and diabetic ketoacidosis occurred in one patient each (0.1%). The incidence of Grade 3-4 hyperglycemia increased consistently in patients with higher body mass index and in patients with higher baseline A1C. Five percent (5%) of patients required initiation of insulin therapy for treatment of hyperglycemia. The median time to onset of hyperglycemia was 0.6 months (range: 0.1 to 20 months). Hyperglycemia led to discontinuation of PADCEV in 0.4% of patients. Closely monitor blood glucose levels in patients with, or at risk for, diabetes mellitus or hyperglycemia. If blood glucose is elevated (>250 mg/dL), withhold PADCEV.

Pneumonitis/Interstitial Lung Disease (ILD) Severe, life-threatening or fatal pneumonitis/ILD occurred in patients treated with PADCEV. In clinical trials of PADCEV as a single agent, 2.9% of the 753 patients treated with PADCEV had pneumonitis/ILD of any grade and 0.8% had Grade 3-4. The median time to onset of pneumonitis/ILD was 2.7 months (range: 0.6 to 6 months). The incidence of pneumonitis/ILD, including severe events occurred at a higher rate when PADCEV was given in combination with pembrolizumab. When PADCEV was given in combination with pembrolizumab, 9% of the 121 patients treated with combination therapy had pneumonitis/ILD of any grade and 3.3% had Grade 3. A fatal event of pneumonitis occurred in one patient (0.8%). The median time to onset of pneumonitis/ILD was 6 months (range: 0.6 to 26 months). Monitor patients for signs and symptoms indicative of pneumonitis/ILD such as hypoxia, cough, dyspnea or interstitial infiltrates on radiologic exams. Evaluate and exclude infectious, neoplastic and other causes for such signs and symptoms through appropriate investigations. Withhold PADCEV for patients who develop Grade 2 pneumonitis/ILD and consider dose reduction. Permanently discontinue PADCEV in all patients with Grade 3 or 4 pneumonitis/ILD.

Peripheral neuropathy (PN) Peripheral neuropathy occurred in 53% of the 753 patients treated with PADCEV as a single agent in clinical trials including 40% with sensory neuropathy, 7% with muscular weakness and 7% with motor neuropathy. Thirty percent of patients experienced Grade 2 reactions and 5% experienced Grade 3-4 reactions. Peripheral neuropathy occurred in patients treated with PADCEV with or without preexisting peripheral neuropathy. The median time to onset of Grade ≥2 peripheral neuropathy was 4.9 months (range: 0.1 to 20 months). Neuropathy led to treatment discontinuation in 7% of patients. Of the patients who experienced neuropathy who had data regarding resolution (N = 319), 14% had complete resolution, 46% had partial improvement, and 40% had no improvement at the time of their last evaluation. Of the 86% of patients with residual neuropathy at last evaluation, 51% had Grade 2 or greater neuropathy at the time of their last evaluation.

The incidence of peripheral neuropathy occurred at a higher rate when PADCEV was given in combination with pembrolizumab. When PADCEV was given in combination with pembrolizumab, 65% of the 121 patients treated with combination therapy had peripheral neuropathy of any grade, 45% had Grade 2 neuropathy, and 3.3% had Grade 3 neuropathy. The median time to onset of Grade ≥2 peripheral neuropathy was 6 months (range: 0.3 to 25 months).

Monitor patients for symptoms of new or worsening peripheral neuropathy and consider dose interruption or dose reduction of PADCEV when peripheral neuropathy occurs. Permanently discontinue PADCEV in patients who develop Grade ≥3 peripheral neuropathy.

Ocular disorders were reported in 40% of the 384 patients treated with PADCEV as a single agent in clinical trials in which ophthalmologic exams were scheduled. The majority of these events involved the cornea and included events associated with dry eye such as keratitis, blurred vision, increased lacrimation, conjunctivitis, limbal stem cell deficiency, and keratopathy. Dry eye symptoms occurred in 34% of patients, and blurred vision occurred in 13% of patients, during treatment with PADCEV. The median time to onset to symptomatic ocular disorder was 1.6 months (range: 0 to 19 months). Monitor patients for ocular disorders. Consider artificial tears for prophylaxis of dry eyes and ophthalmologic evaluation if ocular symptoms occur or do not resolve. Consider treatment with ophthalmic topical steroids, if indicated after an ophthalmic exam. Consider dose interruption or dose reduction of PADCEV for symptomatic ocular disorders.

Infusion site extravasation Skin and soft tissue reactions secondary to extravasation have been observed after administration of PADCEV. Of the 753 patients treated with PADCEV as a single agent in clinical trials, 1.5% of patients experienced skin and soft tissue reactions, including 0.3% who experienced Grade 3-4 reactions. Reactions may be delayed. Erythema, swelling, increased temperature, and pain worsened until 2-7 days after extravasation and resolved within 1-4 weeks of peak. Two patients (0.3%) developed extravasation reactions with secondary cellulitis, bullae, or exfoliation. Ensure adequate venous access prior to starting PADCEV and monitor for possible extravasation during administration. If extravasation occurs, stop the infusion and monitor for adverse reactions.

Embryo-fetal toxicity PADCEV can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risk to the fetus. Advise female patients of reproductive potential to use effective contraception during PADCEV treatment and for 2 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with PADCEV and for 4 months after the last dose.

Adverse Reactions
Most common adverse reactions, including laboratory abnormalities (≥20%) (PADCEV monotherapy)

Rash, aspartate aminotransferase increased, glucose increased, creatinine increased, fatigue, peripheral neuropathy, lymphocytes decreased, alopecia, decreased appetite, hemoglobin decreased, diarrhea, sodium decreased, nausea, pruritus, phosphate decreased, dysgeusia, alanine aminotransferase increased, anemia, albumin decreased, neutrophils decreased, urate increased, lipase increased, platelets decreased, weight decreased and dry skin.

EV-301 Study: 296 patients previously treated with a PD-1/L1 inhibitor and platinum-based chemotherapy.

Serious adverse reactions occurred in 47% of patients treated with PADCEV; the most common (≥2%) were urinary tract infection, acute kidney injury (7% each) and pneumonia (5%). Fatal adverse reactions occurred in 3% of patients, including multiorgan dysfunction (1.0%), hepatic dysfunction, septic shock, hyperglycemia, pneumonitis and pelvic abscess (0.3% each). Adverse reactions leading to discontinuation occurred in 17% of patients; the most common (≥2%) were PN (5%) and rash (4%). Adverse reactions leading to dose interruption occurred in 61% of patients; the most common (≥4%) were PN (23%), rash (11%) and fatigue (9%). Adverse reactions leading to dose reduction occurred in 34% of patients; the most common (≥2%) were PN (10%), rash (8%), decreased appetite and fatigue (3% each). Clinically relevant adverse reactions (<15%) include vomiting (14%), AST increased (12%), hyperglycemia (10%), ALT increased (9%), pneumonitis (3%) and infusion site extravasation (0.7%).

EV-201, Cohort 2 Study: 89 patients previously treated with a PD-1/L1 inhibitor and not eligible for cisplatin-based chemotherapy.

Serious adverse reactions occurred in 39% of patients treated with PADCEV; the most common (≥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 (1.1% each). Adverse reactions leading to discontinuation occurred in 20% of patients; the most common (≥2%) was PN (7%). Adverse reactions leading to dose interruption occurred in 60% of patients; the most common (≥3%) were PN (19%), rash (9%), fatigue (8%), diarrhea (5%), AST increasedand hyperglycemia (3% each). Adverse reactions leading to dose reduction occurred in 49% of patients; the most common (≥3%) were PN (19%), rash (11%) and fatigue (7%). Clinically relevant adverse reactions (<15%) include vomiting (13%), AST increased (12%), lipase increased (11%), ALT increased (10%), pneumonitis (4%) and infusion site extravasation (1%).

EV-103 Study: 121 patients with previously untreated locally advanced or metastatic urothelial cancer who were not eligible for cisplatin-containing chemotherapy (PADCEV in combination with pembrolizumab)

The most common adverse reactions including laboratory abnormalities (≥20%), of PADCEV in combination with pembrolizumab were glucose increased, aspartate aminotransferase increased, rash, hemoglobin decreased, creatinine increased, peripheral neuropathy, lymphocytes decreased, fatigue, alanine aminotransferase increased, sodium decreased, lipase increased, albumin decreased, alopecia, phosphate decreased, decreased weight, diarrhea, pruritus, decreased appetite, nausea, dysgeusia, potassium decreased, neutrophils decreased, urinary tract infection, constipation, potassium increased, calcium increased, peripheral edema, dry eye, dizziness, arthralgia, and dry skin.

Serious adverse reactions occurred in 50% of patients treated with PADCEV in combination with 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 (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 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%), lipase increased (6%), pneumonitis (6%), diarrhea (4.1%), acute kidney injury (3.3%), alanine aminotransferase increased (3.3%), fatigue (3.3%), neutropenia (3.3%), urinary tract infection (3.3%), amylase increased (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%).

Drug Interactions

Effects of other drugs on PADCEV (Dual P-gp and Strong CYP3A4 Inhibitors)

Concomitant use with dual P-gp and strong CYP3A4 inhibitors may increase unconjugated monomethyl auristatin E exposure, which may increase the incidence or severity of PADCEV toxicities. Closely monitor patients for signs of toxicity when PADCEV is given concomitantly with dual P-gp and strong CYP3A4 inhibitors.

Specific Populations

Lactation Advise lactating women not to breastfeed during treatment with PADCEV and for at least 3 weeks after the last dose.

Hepatic impairment Avoid the use of PADCEV in patients with moderate or severe hepatic impairment.

¹ Morgans AK, Hepp Z, Shah SN, et al. Real-world burden of illness and unmet need in locally advanced or metastatic urothelial carcinoma following discontinuation of PD-1/L1 inhibitor therapy: a Medicare claims database analysis. Urol Oncol 2021;39(10):733.e1-e10.

² Galsky MD, Hahn NM, Rosenberg J, et al. Treatment of patients with metastatic urothelial cancer "unfit" for cisplatin-based chemotherapy. J Clin Oncol2011;29(17):2432-8.

³ National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines): bladder cancer version 3.2023 (05-25-2023). https://www.nccn.org/professionals/physician_gls/pdf/bladder.pdf. Accessed 05-25-2023.

⁴ Dorff TB, Groshen S, Garcia A, et al. Safety and feasibility of fasting in combination with platinum-based chemotherapy. BMC Cancer (Epub) 06-10-2016.

⁵ Padcev [package insert]. Northbrook, IL: Astellas Pharma US, Inc.

⁶ National Cancer Institute. NCI dictionary of cancer terms: antibody-drug conjugate. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/antibody-drug-conjugate. Accessed 02-06-2023.

⁷ Xu S. Internalization, trafficking, intracellular processing and actions of antibody-drug conjugates. Pharm Res 2015;32(11):3577-83.

⁸ Challita-Eid PM, Satpayev D, Yang P, et al. Enfortumab vedotin antibody-drug conjugate targeting nectin-4 is a highly potent therapeutic agent in multiple preclinical cancer models. Cancer Res 2016;76(10):3003-13.

⁹ U.S. Food & Drug Administration. FDA grants regular approval to enfortumab vedotin-ejfv for locally advanced or metastatic urothelial cancer. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-regular-approval-enfortumab-vedotin-ejfv-locally-advanced-or-metastatic-urothelial-cancer. Accessed 09-14-2022.

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