E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with locally advanced or metastatic urothelial cancer. |
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E.1.1.1 | Medical condition in easily understood language |
Locally advanced or metastatic urothelial cancer |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10046714 |
E.1.2 | Term | Urothelial carcinoma bladder |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10046723 |
E.1.2 | Term | Urothelial carcinoma ureter |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10046728 |
E.1.2 | Term | Urothelial carcinoma urethra |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10064467 |
E.1.2 | Term | Urothelial carcinoma |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10077056 |
E.1.2 | Term | Urothelial carcinoma recurrent |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10077840 |
E.1.2 | Term | Urothelial cancer of renal pelvis |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10046715 |
E.1.2 | Term | Urothelial carcinoma bladder recurrent |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10046721 |
E.1.2 | Term | Urothelial carcinoma bladder stage III |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10046722 |
E.1.2 | Term | Urothelial carcinoma bladder stage IV |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10046725 |
E.1.2 | Term | Urothelial carcinoma ureter metastatic |
E.1.2 | System Organ Class | 100000004864 |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10046726 |
E.1.2 | Term | Urothelial carcinoma ureter recurrent |
E.1.2 | System Organ Class | 100000004864 |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10046730 |
E.1.2 | Term | Urothelial carcinoma urethra metastatic |
E.1.2 | System Organ Class | 100000004864 |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10046731 |
E.1.2 | Term | Urothelial carcinoma urethra recurrent |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine the antitumor activity of single-agent enfortumab vedotin as measured by confirmed ORR in patients with locally advanced or metastatic urothelial cancer who have previously received systemic therapy with a CPI and either previously received platinum-containing chemotherapy or are platinum-naïve and cisplatin-ineligible
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E.2.2 | Secondary objectives of the trial |
● To assess DOR
● To assess disease control rate (DCR)
● To assess PFS
● To assess OS
● To assess the safety and tolerability of enfortumab vedotin
● To assess the pharmacokinetics (PK) of enfortumab vedotin
● To assess the incidence of antitherapeutic antibodies (ATA) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Histologically documented urothelial (previously known as transitional cell) 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. 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. A CPI is defined as a programmed cell death protein 1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor.
• Must be one of the following:
a. Platinum-treated (Cohort 1): Patients who received prior treatment with platinumcontaining chemotherapy defined as those who received platinum in the adjuvant/neoadjuvant 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;
OR
b.Platinum-naïve and cisplatin ineligible (Cohort 2): Patients who have not received prior treatment with platinum-containing or other chemotherapy in the locally advanced or metastatic setting and are ineligible for treatment with cisplatin at time of enrollment due to one of the following: ECOG performance status score of 2; impaired renal function (defined as creatinine clearance [CrCl] ≥30 and <60 mL/min), or a ≥ Grade 2 hearing loss. Patients who received platinum in the adjuvant/neoadjuvant setting and did not progress within 12 months of completion will be considered platinum-naïve.
• 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.
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E.4 | Principal 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 monomethyl auristatin E (MMAE)-based antibody-drug conjugates (ADCs).
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of this study is the confirmed Objective Response
Rate (ORR) per IRF. The ORR is defined as the
proportion of patients with confirmed CR or PR according to RECIST
Version 1.1 . Patients who do not have at least 2 (initial response and
confirmation scan) post-baseline response assessments as described in
Section 7.2 of the
protocol will be counted as non-responders.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
The key secondary endpoints are:
- Duration of Response (DOR);
- Disease Control Rate at Week 16 (DCR16);
- Progression-free Survival (PFS);
- Overall Survival (OS);
-ORR per investigator.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 17 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
France |
Germany |
Italy |
Japan |
Korea, Republic of |
Netherlands |
Spain |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The study will be closed 5 years after enrollment of the last patient, or when no patients remain in long-term follow-up, whichever occurs first. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 6 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 26 |
E.8.9.2 | In all countries concerned by the trial years | 7 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |