A Study to Evaluate Enfortumab Vedotin (ASG-22CE) in Chinese Participants With Locally Advanced or Metastatic Urothelial Cancer Who Previously Received Platinum-containing Chemotherapy and Programmed Cell Death Protein-1 ( PD 1) / (Programmed Death Ligand-1 (PD-L1) Inhibitor Therapy

NCT04995419 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 7465-CL-1104CTR20210922
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 7

Brief Summary

The purpose of this study was to determine the antitumor activity of enfortumab vedotin (EV) confirmed by the objective response rate (ORR). This study also evaluated the effect of antibody-drug conjugate (ADC), total antibody (TAb) and monomethyl auristatin E (MMAE) in Chinese participants with locally advanced or metastatic urothelial cancer. In addition, the study also evaluated the duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and immunogenicity determined by the incidence of antitherapeutic antibodies (ATA). Safety and tolerability of EV in participants with locally advanced or metastatic urothelial cancer was also evaluated.

Conditions

Metastatic Urothelial Cancer

Keywords

Enfortumab Vedotin; PADCEV; ASG-22CE; Pharmacokinetics; Urothelial cancer

Outcome Measures

Primary Outcomes (22)

• Objective Response Rate (ORR) as Per Response Evaluation Criteria in Solid Tumors V1.1 (RECIST V1.1)

  ORR was defined as the percentage of participants with best overall response (BOR) as complete response (CR) or partial response (PR) based on the RECIST v1.1. CR was defined as disappearance of all target and nontarget lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to \< 10 mm from baseline measurement. PR was defined as at least a 30% decrease in the sum of diameters (longest for nonnodal lesions, short axis for nodal lesions) of target lesions taking as reference to the baseline sum of diameters.

  From first dose up to progressive disease or death (maximum duration: 9.33 months)

• Pharmacokinetics (PK) of Antibody-Drug Conjugate (ADC), Total Antibody (TAb), in Serum: Maximum Concentration (Cmax) at Cycle 1 Day 1

  Cmax was derived from the PK blood samples collected.

  Cycle 1 Day 1: pre-dose, end of infusion (EOI), 2 hour, 4 hour post-dose (each cycle = 28 days)

• PK of Monomethyl Auristatin E (MMAE) in Serum: Maximum Concentration (Cmax) at Cycle 1 Day 1

  Cmax was derived from the PK blood samples collected.

  Cycle 1 Day 1: pre-dose, end of infusion (EOI), 2 hour, 4 hour post-dose (each cycle = 28 days)

• PK of ADC, TAb in Serum: Maximum Concentration (Cmax) at Cycle 1 Day 15

  Cmax was derived from the PK blood samples collected.

  Cycle 1 Day 15: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)

• PK of MMAE in Serum: Maximum Concentration (Cmax) at Cycle 1 Day 15

  Cmax was derived from the PK blood samples collected.

  Cycle 1 Day 15: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)

• PK of ADC , TAb in Serum: Trough Concentration (Ctrough) at Cycle 1 Day 1

  As per planned analysis, if more than 50% of PK concentrations were below the limit of quantification (i.e 0) at a given time point, standard deviation was not reported.

  Cycle 1 Day 1: pre-dose

• PK of MMAE in Serum: Trough Concentration (Ctrough) at Cycle 1 Day 1

  As per planned analysis, if more than 50% of PK concentrations were below the limit of quantification (i.e 0) at a given time point, standard deviation was not reported.

  Cycle 1 Day 1: pre-dose

• PK of ADC, TAb in Serum: Trough Concentration (Ctrough) at Cycle 1 Day 15

  Ctrough was derived from the PK blood samples collected.

  Cycle 1 Day 15: pre-dose

• PK of MMAE in Serum: Trough Concentration (Ctrough) at Cycle 1 Day 15

  Ctrough was derived from the PK blood samples collected.

  Cycle 1 Day 15: pre-dose

• PK of ADC, TAb, MMAE in Serum: Time to Maximum Concentration (Tmax) at Cycle 1 Day 1

  Tmax was derived from the PK blood samples collected.

  Cycle 1 Day 1: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)

• PK of ADC, TAb, MMAE in Serum: Time to Maximum Concentration (Tmax) at Cycle 1 Day 15

  Tmax was derived from the PK blood samples collected.

  Cycle 1 Day 15: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)

• PK of ADC, TAb, MMAE in Serum: Area Under Concentration-time Curve From 0 to Day 28 (AUC0-28d) at Cycle 1 Day 1

  AUC0-28d was derived from the PK blood samples collected.

  Cycle 1 Day 1: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)

• PK of ADC, TAb, MMAE in Serum: Area Under Concentration-time Curve From 0 to Day 28 (AUC0-28d) at Cycle 1 Day 15

  AUC0-28d was derived from the PK blood samples collected.

  Cycle 1 Day 15: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)

• PK of ADC, TAb in Serum: Area Under Concentration-time Curve From 0 to Day 7 (AUC0-7d) at Cycle 1 Day 1

  AUC0-7d was derived from the PK blood samples collected.

  Cycle 1 Day 1 : pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)

• PK of MMAE in Serum: Area Under Concentration-time Curve From 0 to Day 7 (AUC0-7d) at Cycle 1 Day 1

  AUC0-7d was derived from the PK blood samples collected.

  Cycle 1 Day 1 : pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)

• PK of ADC, TAb in Serum: Area Under Concentration-time Curve From 0 to Day 7 (AUC0-7d) at Cycle 1 Day 15

  AUC0-7d was derived from the PK blood samples collected.

  Cycle 1 Day 15: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)

• PK of MMAE in Serum: Area Under Concentration-time Curve From 0 to Day 7 (AUC0-7d) at Cycle 1 Day 15

  AUC0-7d was derived from the PK blood samples collected.

  Cycle 1 Day 15: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)

• PK of ADC, TAb, MMAE in Plasma: Accumulation Ratio of Cmax (RacCmax)

  Accumulation ratio is the ratio of Cmax after the dosing interval (Cycle 1 Day 15) divided by Cmax after the first dosing interval (Cycle 1 Day 1).

  Cycle 1 Day 15: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)

• PK of ADC, TAb, MMAE in Serum: Accumulation Ratio of AUC0-7d ( RacAUC0-7d)

  RacAUC0-7d was calculated using AUC0-7d and derived from the PK blood samples collected.

  Cycle 1 Day 15: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)

• PK of ADC, TAb, MMAE in Serum: Terminal Elimination Half-life (t1/2)

  t1/2 was derived from the PK blood samples collected.

  Cycle 1 Day 15: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)

• PK of ADC, TAb, MMAE in Serum: Systemic Clearance (CL)

  CL was derived from the PK blood samples collected.

  Cycle 1 Day 15: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)

• PK of ADC, TAb, MMAE in Serum: Volume of Distribution at Steady State (Vss)

  Vss was derived from the PK blood samples collected.

  Cycle 1 Day 15: pre-dose, EOI, 2 hour, 4 hour post-dose (each cycle = 28 days)

Secondary Outcomes (11)

• Duration of Response (DOR) as Per RECIST V1.1 Per IRC

  From date of the first CR/PR up to progressive disease or death (maximum duration: 9.33 months)

• Duration of Response (DOR) as Per RECIST V1.1 Per Investigator's Assessment

  From date of the first CR/PR up to progressive disease or death (maximum duration: 9.33 months)

• Objective Response Rate (ORR) as Per Investigator Assessment

  From first dose up to progressive disease or death (maximum duration: 9.33 months)

• Disease Control Rate (DCR) as Per RECIST V1.1 Per IRC

  From first dose up to progressive disease or death (maximum duration: 9.33 months)

• Disease Control Rate (DCR) as Per RECIST V1.1 Per Investigator's Assesment

  From first dose up to progressive disease or death (maximum duration: 9.33 months)

Study Arms (1)

Enfortumab Vedotin 1.25 mg/kg

EXPERIMENTAL

Participants received 1.25 milligrams per kilogram (mg/kg) of body weight enfortumab vedotin by intravenous (IV) infusion over approximately 30 minutes on days 1, 8 and 15 of every 28-day cycle. Participants received study treatment until radiological disease progression as determined per investigator assessment or other discontinuation criteria were met or upon study termination, or study completion, whichever occurred first. Participants who had intense PK Sampling were enrolled in PK Cohort.

Drug: Enfortumab vedotin

Interventions

Enfortumab vedotin DRUG

Intravenous Infusion

Also known as: PADCEV, ASG-22CE

Enfortumab Vedotin 1.25 mg/kg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Participant must have histologically or cytologically documented urothelial/transitional cell carcinoma of the bladder, renal pelvis, ureter or urethra. Other histologies including adenocarcinoma, squamous differentiation or mixed are eligible.
• Participant has locally advanced or metastatic disease that is not amenable to curative intent treatment. Participants must have measurable disease at baseline according to Response Evaluation Criteria in Solid Tumors (RECIST) ( Version 1.1). Lesions in a prior radiation field must have progressed subsequent to radiotherapy to be considered measurable.
• Participant must have received prior treatment with PD-1/PD-L1 inhibitor therapy in the locally advanced or metastatic urothelial cancer setting. Participants who received PD-1/PD-L1 therapy in the neoadjuvant/adjuvant setting and had recurrent or progressive disease either during therapy or within 3 months of therapy completion are eligible.
• Participant who received prior treatment with platinum-containing chemotherapy defined as those who received platinum in the neoadjuvant/adjuvant setting and had recurrent or progressive disease within 12 months of completion or received treatment with platinum in the locally advanced (defined as unresectable with curative intent) or metastatic setting.
• Platinum based chemotherapy may include combination use with a PD-1 or PD-L1 inhibitor.
• Participant has the following baseline laboratory data. If a participant has received a recent blood transfusion or growth factor, the hematology tests must be obtained ≥7 days after any growth factor and ≥ 28 days after any blood transfusion.
• absolute neutrophil count (ANC) ≥ 1.0 × 10\^9/L
• platelet count ≥ 100 × 10\^9/L
• hemoglobin ≥ 9 g/dL
• serum total bilirubin (TBL) ≤ 1.5 × upper limit of normal (ULN) or ≤ 3 × ULN for participants with Gilbert's disease
• creatinine clearance (CrCl) ≥ 30 mL/min as estimated per institutional standards or as measured by 24-hour urine collection (glomerular filtration rate \[GFR\] can also be used instead of CrCl).
• alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × ULN
• Female participant is not pregnant and at least one of the following conditions apply:
• Not a woman of childbearing potential (WOCBP)

You may not qualify if:

• Participant has preexisting sensory or motor neuropathy Grade ≥ 2.
• Participant has active central nervous system (CNS) metastases. Participants with treated CNS metastases are permitted on study if all the following are true:
• CNS metastases have been clinically stable for ≥ 6 weeks prior to screening.
• If requiring steroid treatment for CNS metastases, the participant is on a stable dose ≤ 20 mg/day of prednisone or equivalent for ≥ 2 weeks.
• Baseline imaging scans show no evidence of new or enlarged brain metastasis.
• Participant does not have leptomeningeal disease.
• Participant has ongoing clinically significant toxicity (Grade 2 or higher with the exception of alopecia) associated with prior treatment (including systemic therapy, radiotherapy or surgery).
• Participant with ongoing ≥ Grade 3 immunotherapy-related hypothyroidism or panhypopituitarism is excluded. Participant with ongoing immunotherapy-related colitis, uveitis, myocarditis or pneumonitis, or participants with other immunotherapy-related AEs requiring high doses of steroids (\> 20 mg/day of prednisone or equivalent), is excluded. Participant with ≤ Grade 2 immunotherapy-related hypothyroidism or panhypopituitarism may be enrolled when well-maintained/controlled on a stable dose of hormone replacement therapy (if indicated).
• Participant has a history of uncontrolled diabetes mellitus within 3 months before the first dose of study treatment. Uncontrolled diabetes is defined as hemoglobin A1c (HbA1c) ≥ 8 percent or HbA1c between 7 percent and \< 8 percent with associated diabetes symptoms (polyuria or polydipsia) that are not otherwise explained.
• Participant has prior treatment with enfortumab vedotin or other monomethyl auristatin E (MMAE)-based antibody-drug conjugate (ADCs).
• Participant has a second malignancy diagnosed within 3 years before first dose of study drug, or any evidence of residual disease from a previously diagnosed malignancy. Participants with non-melanoma skin cancer, localized prostate cancer treated with curative intent with no evidence of progression, low-risk or very low-risk (per standard guidelines) localized prostate cancer under active surveillance/watchful waiting without intent to treat, or carcinoma in situ of any type (if complete resection was performed) are allowed.
• Participant is currently receiving systemic antimicrobial treatment for viral, bacterial or fungal infection at the time of first dose of study treatment. Routine antimicrobial prophylaxis is permitted.
• Participants with a positive hepatitis B surface antigen and/or anti-hepatitis B core antibody and a negative polymerase chain reaction (PCR) assay at baseline should receive appropriate antiviral prophylaxis or regular surveillance monitoring as per local or institutional guidelines.
• Active hepatitis C infection or known human immunodeficiency virus (HIV) infection. Participant who have been treated for hepatitis C infection are permitted if they have documented sustained virologic response of ≥ 12 weeks.
• Participant has documented history of a cerebral vascular event (stroke or transient ischemic attack), unstable angina, myocardial infarction or cardiac symptoms (including congestive heart failure) consistent with New York Heart Association Class III-IV within 6 months prior to the first dose of study drug.

Sponsors & Collaborators

• Astellas Pharma China, Inc.: lead
• Seagen Inc.: collaborator

Study Sites (7)

Site CN86001

Beijing, China

Location

Site CN86009

Changsha, China

Location

Site CN86002

Guangzhou, China

Location

Site CN86006

Hangzhou, China

Location

Site CN86007

Nanjing, China

Location

Site CN86004

Shanghai, China

Location

Site CN86003

Wuhan, China

Location

Related Publications (1)

• Li S, Shi Y, Dong H, Guo H, Xie Y, Sun Z, Zhang X, Kim E, Zhang J, Li Y, Xu C, Kadeerbai H, Lee S, Gorla S, Guo J, Sheng X. Phase 2 Trial of Enfortumab Vedotin in Patients With Previously Treated Locally Advanced or Metastatic Urothelial Carcinoma in China. Cancer Med. 2024 Nov;13(21):e70368. doi: 10.1002/cam4.70368.

  PMID: 39530574 DERIVED

MeSH Terms

Interventions

enfortumab vedotin

Results Point of Contact

• Title: Clinical Transparency
• Organization: Astellas Pharma China, Inc.

astellas.resultsdisclosure@astellas.com

+86-(0)10-85216666

Study Officials

• Senior Medical Science Manager

  Astellas Pharma China, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 2, 2021
• First Posted: August 9, 2021
• Study Start: July 22, 2021
• Primary Completion: May 13, 2022
• Study Completion: August 27, 2025
• Last Updated: October 7, 2025
• Results First Posted: September 13, 2023

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (7)