Clinical trial NCT03219333: A Study of Enfortumab Vedotin for Patients With Locally Advanced or Metastatic Urothelial Bladder Cancer
Official title: A Single-arm, Open-label, Multicenter Study of Enfortumab Vedotin (ASG-22CE) for Treatment of Patients With Locally Advanced or Metastatic Urothelial Cancer Who Previously Received Immune Checkpoint Inhibitor (CPI) Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Carcinoma, Transitional Cell
Urinary Bladder Neoplasms
Urologic Neoplasms
Renal Pelvis Neoplasms
Urothelial Cancer
Ureteral Neoplasms
Urethral Neoplasms
Keywords: Enfortumab vedotin
Metastatic Urothelial Cancer
ASG-22CE
Locally Advanced Urothelial Cancer
Antibody-Drug Conjugate
Nectin-4
Platinum-naïve
Cisplatin-ineligible
Antineoplastic Agents
Drug Therapy
ASG-22ME
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
Collaborators: name: Seagen Inc.
First posted: 2017-07-17
Enrollment: 219
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: single-arm, open-label, multi-cohort, multicenter study
Primary purpose: TREATMENT

Brief summary: This is a study that will test how an experimental drug (enfortumab vedotin) affects patients with cancer of the urinary system (urothelial cancer). This type of cancer includes cancer of the bladder, renal pelvis, ureter or urethra that has spread to nearby tissues or to other areas of the body.

This clinical trial will enroll patients who were previously treated with a kind of anticancer drug called an immune checkpoint inhibitor (CPI). Some CPIs have been approved for the treatment of urothelial cancer.

This study will test if the cancer shrinks with treatment. This study will also look at the side effects of the drug. A side effect is a response to a drug that is not part of the treatment effect.

Patients who sign up for this trial must also fall into one of these categories:

* Patients have already received treatment with platinum-containing chemotherapy
* Patients have never received platinum-containing treatment and are not eligible for treatment with cisplatin.

Detailed description: Japan Pharmaceuticals and Medical Devices Agency (PMDA) has approved enfortumab vedotin (Padcev) for the treatment of advanced urothelial cancer. The study will continue as a post marketing study in Japan.

This study will examine the safety and anticancer activity of enfortumab vedotin given intravenously to patients with locally advanced or metastatic urothelial cancer who previously received a CPI and either previously received platinum-containing chemotherapy (Cohort 1) or are platinum-naïve and cisplatin-ineligible (Cohort 2). Patients who received platinum in the adjuvant/neoadjuvant setting and did not progress within 12 months of completion will be considered platinum-naïve. Approximately 100 patients are expected to be enrolled in each cohort. The primary goal of the study is to determine the confirmed ORR of enfortumab vedotin.

Eligibility criteria: Inclusion Criteria:

* Histologically documented urothelial carcinoma (squamous differentiation or mixed cell types allowed).
* Metastatic disease or locally advanced disease that is not resectable.
* Must have received prior treatment with a CPI in the locally advanced or metastatic urothelial cancer setting. A CPI is defined as a programmed cell death protein 1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor. Patients who received CPI therapy in the neoadjuvant/adjuvant setting and had recurrent or progressive disease either during therapy or within 3 months of therapy completion are eligible.
* Must either have prior treatment with platinum-containing chemotherapy (Cohort 1) or be platinum-naïve and ineligible for treatment with cisplatin at time of enrollment (Cohort 2).
* Must have had progression or recurrence of urothelial cancer during or following receipt of most recent therapy.
* Tumor tissue samples must be available for submission to the sponsor prior to study treatment.
* Must have measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) (Version 1.1).
* An Eastern Cooperative Oncology Group (ECOG) Performance Status score of ≤1 for Cohort 1 or ≤2 for Cohort 2.
* Anticipated life expectancy of ≥3 months as assessed by the investigator.

Exclusion Criteria:

* Ongoing sensory or motor neuropathy Grade ≥2.
* Active central nervous system (CNS) metastases.
* Immunotherapy related myocarditis, colitis, uveitis, or pneumonitis.
* Prior enrollment in an enfortumab vedotin study or prior treatment with other monomethyl auristatin E (MMAE)-based antibody-drug conjugates (ADCs).
* Uncontrolled tumor-related pain or impending spinal cord compression.

Primary outcomes:
measure: Objective Response Rate (ORR) Per Blinded Independent Central Review (BICR)
timeFrame: Cohort 1: median follow-up time: 10.15 months (range 0.49, 16.46); Cohort 2: median follow up time: 13.4 months (range 0.33 to 29.27)
Secondary outcomes:
measure: Duration of Objective Response (DOR) Per BICR
timeFrame: Cohort 1: median follow-up time: 10.15 months (range 0.49, 16.46); Cohort 2: median follow up time: 13.4 months (range 0.33 to 29.27)
measure: Progression-Free Survival (PFS) Per BICR
timeFrame: Cohort 1: median follow-up time: 10.15 months (range 0.49, 16.46); Cohort 2: median follow up time: 13.4 months (range 0.33 to 29.27)
measure: ORR Per Investigator Assessment
timeFrame: Cohort 1: median follow-up time: 10.15 months (range 0.49, 16.46); Cohort 2: median follow up time: 13.4 months (range 0.33 to 29.27)
measure: DOR Per Investigator Assessment
timeFrame: Cohort 1: median follow-up time: 10.15 months (range 0.49, 16.46); Cohort 2: median follow up time: 13.4 months (range 0.33 to 29.27)
measure: PFS Per Investigator Assessment
timeFrame: Cohort 1: median follow-up time: 10.15 months (range 0.49, 16.46); Cohort 2: median follow up time: 13.4 months (range 0.33 to 29.27)
measure: Number of Participants With Treatment-Emergent Laboratory Abnormalities (Hematology)
timeFrame: The median duration of treatment was 4.60 months for Cohort 1 [range: 0.5, 29.4 months] and 5.98 months for Cohort 2 [range: 0.3, 24.6 months]
measure: Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry)
timeFrame: The median duration of treatment was 4.60 months for Cohort 1 [full range: 0.5, 29.4 months] and 5.98 months for Cohort 2 [full range: 0.3, 24.6 months]
measure: Incidence of Antitherapeutic Antibody (ATA)
timeFrame: The median duration of treatment was 4.60 months for Cohort 1 [full range: 0.5, 29.4 months] and 5.98 months for Cohort 2 [full range: 0.3, 24.6 months]
measure: Disease Control Rate at 16 Weeks (DCR16) Per BICR
timeFrame: Up to Week 16
measure: DCR16 Per Investigator Assessment
timeFrame: Up to Week 16
measure: Overall Survival (OS): Primary Analysis
timeFrame: Cohort 1 median follow-up time: 28.4 months [range 0.49, 32.62]; Cohort 2 median follow up time: 13.4 months [range 0.33 to 29.27]
measure: Number of Participants With Adverse Events (AEs): Primary Analysis
timeFrame: The median duration of treatment was 4.60 months for Cohort 1 [range: 0.5, 29.4 months] and 5.98 months for Cohort 2 [range: 0.3, 24.6 months]
measure: Pharmacokinetics (PK) Parameter for Enfortumab Vedotin: Maximum Concentration (Cmax) (Serum)
timeFrame: Collected during cycle 1 and 2 of treatment (each cycle=28 days) at Day 1 pre-dose and end of infusion, Day 3, Day 8 pre-dose and end of infusion, Day 15 pre-dose and end of infusion, Day 17, and Day 22
measure: PK Parameter for Enfortumab Vedotin: Time to Maximum Concentration (Tmax) (Serum)
timeFrame: Collected during cycle 1 and 2 of treatment (each cycle=28 days) at Day 1 pre-dose and end of infusion, Day 3, Day 8 pre-dose and end of infusion, Day 15 pre-dose and end of infusion, Day 17, and Day 22
measure: PK Parameter for Enfortumab Vedotin: Area Under Concentration-Time Curve (AUC) (Serum)
timeFrame: AUC0-7 was assessed (in cycles 1 and 2) based on concentration data from Day 1 to Day 8 (pre dose) and AUC0-14 was assessed based on data from D15 (pre dose) to D29 (pre-dose)
measure: PK Parameter for Free Monomethyl Auristatin E (MMAE): Cmax (Plasma)
timeFrame: Collected during cycle 1 and 2 of treatment (each cycle=28 days) at Day 1 pre-dose and end of infusion, Day 3, Day 8 pre-dose and end of infusion, Day 15 pre-dose and end of infusion, Day 17, and Day 22
measure: PK Parameter for Free MMAE: Tmax (Plasma)
timeFrame: Collected during cycle 1 and 2 of treatment (each cycle=28 days) at Day 1 pre-dose and end of infusion, Day 3, Day 8 pre-dose and end of infusion, Day 15 pre-dose and end of infusion, Day 17, and Day 22
measure: PK Parameter for Free MMAE: AUC (Plasma)
timeFrame: AUC0-7 was assessed (in cycles 1 and 2) based on concentration data from Day 1 to Day 8 (pre dose) and AUC0-14 was assessed based on data from D15 (pre dose) to D29 (pre-dose)
measure: PK Parameter for Total Antibody (TAb): Cmax (Serum)
timeFrame: Collected during cycle 1 and 2 of treatment (each cycle=28 days) at Day 1 pre-dose and end of infusion, Day 3, Day 8 pre-dose and end of infusion, Day 15 pre-dose and end of infusion, Day 17, and Day 22
measure: PK Parameter for TAb: Tmax (Serum)
timeFrame: Collected during cycle 1 and 2 of treatment (each cycle=28 days) at Day 1 pre-dose and end of infusion, Day 3, Day 8 pre-dose and end of infusion, Day 15 pre-dose and end of infusion, Day 17, and Day 22
measure: PK Parameter for TAb: AUC (Serum)
timeFrame: AUC0-7 was assessed (in cycles 1 and 2) based on concentration data from Day 1 to Day 8 (pre dose) and AUC0-14 was assessed based on data from D15 (pre dose) to D29 (pre-dose)
measure: Number of Participants With Adverse Events (AEs): Final Analysis
timeFrame: Cohort 1: median treatment duration time: 4.60 months (range 0.5, 43.0); Cohort 2: median treatment duration time: 5.98 months (range 0.3 to 25.8)
measure: Overall Survival (OS): Final Analysis
timeFrame: Cohort 1: median follow-up: 61.0 months (range 59.63, 62.36); Cohort 2: median follow-up time: 45.8 months (range 44.91 to 48.95)
Other outcomes:
Locations:
city: Anchorage
country: United States
facility: Alaska Urological Institute
state: Alaska
city: Goodyear
country: United States
facility: Arizona Oncology Associates, PC - HAL
state: Arizona
city: Phoenix
country: United States
facility: Mayo Clinic Arizona
state: Arizona
city: Tucson
country: United States
facility: Arizona Oncology Associates, PC - HOPE
state: Arizona
city: Los Angeles
country: United States
facility: Keck Medical Center / University of Southern California
state: California
city: Newport Beach
country: United States
facility: Keck Medical Center / Newport Beach
state: California
city: Oakland
country: United States
facility: Kaiser Permanente Oakland
state: California
city: Orange
country: United States
facility: Chao Family Comprehensive Cancer Center University of California Irvine
state: California
city: Orange
country: United States
facility: University of California Irvine - Newport
state: California
city: Roseville
country: United States
facility: Kaiser Permanente Roseville
state: California
city: Sacramento
country: United States
facility: University of California Davis
state: California
city: Sacramento
country: United States
facility: Kaiser Permanente Sacramento
state: California
city: San Francisco
country: United States
facility: Kaiser Permanente San Francisco
state: California
city: San Jose
country: United States
facility: Kaiser Permanente San Jose
state: California
city: San Leandro
country: United States
facility: Kaiser Permanente San Leandro
state: California
city: Santa Clara
country: United States
facility: Kaiser Permanente Santa Clara
state: California
city: South San Francisco
country: United States
facility: Kaiser Permanente South San Francisco
state: California
city: Vallejo
country: United States
facility: Kaiser Permanente Medical Center Northern California
state: California
city: Walnut Creek
country: United States
facility: Kaiser Permanente Walnut Creek
state: California
city: Aurora
country: United States
facility: Rocky Mountain Cancer Centers - Aurora
state: Colorado
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Ocala
country: United States
facility: Ocala Oncology Center
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center & Research Institute
state: Florida
city: Augusta
country: United States
facility: Augusta University
state: Georgia
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Louisville
country: United States
facility: Norton Cancer Institute, St. Matthews Campus
state: Kentucky
city: Baltimore
country: United States
facility: Johns Hopkins Medical Center
state: Maryland
city: Rockville
country: United States
facility: Maryland Oncology Hematology, P.A.
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Institute / Wayne State University
state: Michigan
city: Saint Louis
country: United States
facility: Washington University in St Louis
state: Missouri
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Albany
country: United States
facility: New York Oncology Hematology, P.C.
state: New York
city: New York
country: United States
facility: New York University (NYU) Cancer Institute
state: New York
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Rochester
country: United States
facility: James P. Wilmot Cancer Center / University of Rochester Medical Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: James Cancer Hospital / Ohio State University
state: Ohio
city: Tigard
country: United States
facility: Northwest Cancer Specialists, P.C.
state: Oregon
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center (UPMC)/Hillman Cancer Center
state: Pennsylvania
city: Greenville
country: United States
facility: Prisma Health
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Austin
country: United States
facility: Texas Oncology - Austin Central
state: Texas
city: Dallas
country: United States
facility: Texas Oncology - Baylor Sammons Cancer Center
state: Texas
city: Houston
country: United States
facility: Houston Methodist Cancer Center
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Fairfax
country: United States
facility: Virginia Cancer Specialists, PC
state: Virginia
city: Norfolk
country: United States
facility: Virginia Oncology Associates
state: Virginia
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance / University of Washington
state: Washington
city: Villejuif-Cedex-France
country: France
facility: Site FR33001
city: Muenster
country: Germany
facility: Site DE49004
city: Tübingen
country: Germany
facility: Site DE49001
city: Milano
country: Italy
facility: Site IT39001
city: Terni
country: Italy
facility: Site IT39003
city: Hirosaki
country: Japan
facility: Site JP81001
state: Aomori
city: Tsukuba
country: Japan
facility: Site JP81004
state: Ibaraki
city: Morioka
country: Japan
facility: Site JP81002
state: Iwate
city: Osakasayama
country: Japan
facility: Site JP81008
state: Osaka
city: Shinjuku-ku
country: Japan
facility: Site JP81006
state: Tokyo
city: Ube
country: Japan
facility: Site JP81009
state: Yamaguchi
city: Chiba
country: Japan
facility: Site JP81005
city: Fukuoka
country: Japan
facility: Site JP81011
city: Fukuoka
country: Japan
facility: Site JP81012
city: Nigata
country: Japan
facility: Site JP81003
city: Osaka
country: Japan
facility: Site JP81007
city: Tokushima
country: Japan
facility: Site JP81010
city: Daejeon
country: Korea, Republic of
facility: Site KR82005
city: Seongnam-si
country: Korea, Republic of
facility: Site KR82003
city: Seoul
country: Korea, Republic of
facility: Site KR82001
city: Seoul
country: Korea, Republic of
facility: Site KR82002
city: Seoul
country: Korea, Republic of
facility: Site KR82004
city: Amsterdam
country: Netherlands
facility: Site NL31001
city: Barcelona
country: Spain
facility: Site ES34002
city: Barcelona
country: Spain
facility: Site ES34005
city: Santander
country: Spain
facility: Site ES34003
city: Sevilla
country: Spain
facility: Site ES34004
Study officials:
affiliation: Seagen Inc.
name: Janet Trowbridge, MD, PhD
role: STUDY_DIRECTOR
References:
citation: McGregor B, O'Donnell PH, Balar A, Petrylak D, Rosenberg J, Yu EY, Quinn DI, Heath EI, Campbell M, Hepp Z, McKay C, Steinberg J, Regnault A, Mazerolle F, Galsky MD. Health-related Quality of Life of Patients with Locally Advanced or Metastatic Urothelial Cancer Treated with Enfortumab Vedotin after Platinum and PD-1/PD-L1 Inhibitor Therapy: Results from Cohort 1 of the Phase 2 EV-201 Clinical Trial. Eur Urol. 2022 May;81(5):515-522. doi: 10.1016/j.eururo.2022.01.032. Epub 2022 Feb 12.
citation: Yu EY, Petrylak DP, O'Donnell PH, Lee JL, van der Heijden MS, Loriot Y, Stein MN, Necchi A, Kojima T, Harrison MR, Hoon Park S, Quinn DI, Heath EI, Rosenberg JE, Steinberg J, Liang SY, Trowbridge J, Campbell M, McGregor B, Balar AV. Enfortumab vedotin after PD-1 or PD-L1 inhibitors in cisplatin-ineligible patients with advanced urothelial carcinoma (EV-201): a multicentre, single-arm, phase 2 trial. Lancet Oncol. 2021 Jun;22(6):872-882. doi: 10.1016/S1470-2045(21)00094-2. Epub 2021 May 12.
citation: Rosenberg JE, O'Donnell PH, Balar AV, McGregor BA, Heath EI, Yu EY, Galsky MD, Hahn NM, Gartner EM, Pinelli JM, Liang SY, Melhem-Bertrandt A, Petrylak DP. Pivotal Trial of Enfortumab Vedotin in Urothelial Carcinoma After Platinum and Anti-Programmed Death 1/Programmed Death Ligand 1 Therapy. J Clin Oncol. 2019 Oct 10;37(29):2592-2600. doi: 10.1200/JCO.19.01140. Epub 2019 Jul 29.