| Titre |
A Study of Enfortumab Vedotin (ASG-22CE) as Monotherapy or in Combination With Other Anticancer Therapies for the Treatment of Urothelial Cancer |
| Protocole ID |
SGN22E-002 (MK-3475-869/KEYNOTE KN-869) |
| ClinicalTrials.gov ID |
NCT03288545 |
| Type(s) de cancer |
Vessie/urothélial |
| Phase |
Phase I-II |
| Type étude |
Clinique |
| Médicament |
Enfortumab védotine seul ou en association avec d'autres thérapies |
| Institution |
CIUSSS DE L'ESTRIE – CENTRE HOSP. UNIV. DE SHERBROOKE
 HOPITAL FLEURIMONT
3001 12e Avenue Nord, Sherbrooke, QC, J1H 5N4
|
| Ville |
Sherbrooke |
| Investigateur(trice) principal(e) |
Dr Michel Pavic
|
| Coordonnateur(trice) |
Anick Champoux
819-346-1110 poste 12811
|
| Statut |
![]() Fermé |
| Critètes d'éligibilité |
-
Locally advanced or metastatic urothelial cancer (la/mUC) - Cohorts A, B, D, E, F, G and K.
- Histologically documented la/mUC, including squamous differentiation or mixed cell types.
- An Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, 1 or 2: Participants with ECOG performance status of 2 must meet the following additional criteria: hemoglobin ≥10 g/dL, GFR ≥50 mL/min, may not have NYHA Class III heart failure.
- Eligible for pembrolizumab (Dose-escalation cohorts, Cohorts A, B, G and K Combination Arm).
- Dose-escalation cohorts: Ineligible for first-line cisplatin-based chemotherapy and no prior treatment for la/mUC, or have disease progression following at least 1 platinum-containing treatment.
- Cohort A: Ineligible for cisplatin-based chemotherapy and no prior treatment for la/mUC. No prior adjuvant/neoadjuvant platinum-based therapy in at least 12 months.
- Cohort B: Must have disease progression during/following treatment with at least 1 platinum-containing regimen for la/mUC or disease recurrence.
- Cohort D: Eligible for cisplatin-based chemotherapy and no prior treatment for la/mUC. No prior adjuvant/neoadjuvant platinum-based therapy in at least 12 months.
- Cohort E: Ineligible for cisplatin-based chemotherapy, eligible for carboplatin, and no prior treatment for la/mUC. No prior adjuvant/neoadjuvant platinum-based therapy in at least 12 months.
- Cohort F: Ineligible for platinum-based chemotherapy, or disease progression during/following at least 1 prior treatment for la/mUC. Eligible for gemcitabine.
- Cohort G: Eligible for platinum-based chemotherapy (either cisplatin or carboplatin) and no prior treatment for la/mUC. No prior adjuvant/neoadjuvant platinum-based therapy in at least 12 months.
- Cohort K: Ineligible for cisplatin-based chemotherapy due to at least 1 of the following: Glomerular filtration rate (GFR) <60 mL/min and ≥30 mL/min, ECOG performance status of 2, NCI CTCAE Version 4.03 Grade ≥2 hearing loss, New York Heart Association (NYHA) Class III heart failure. No prior systemic treatment for locally advanced or metastatic disease. No adjuvant/neoadjuvant platinum-based therapy within 12 months prior to randomization.
-
Muscle Invasive Bladder Cancer (MIBC)- Cohorts H, J and L.
- Histologically confirmed MIBC with predominant >50% urothelial histology:Cohorts H and J: Clinical stage cT2-T4aN0M0; Cohort L: Clinical stage cT2-T4aN0M0 or cT1-T4aN1M0: Participants with pT1 disease are eligible only if they have N1 disease on imaging. Mixed cell types are eligible if urothelial cancer is predominant (>50%); Participants with plasmacytoid and/or neuroendocrine tumors are ineligible regardless of component percentage.
- Must be cisplatin-ineligible.
- Cohort-specific eligibility: Cohort J, H, and L: No prior systemic treatment, chemoradiation, or radiation therapy for MIBC. May have received prior intravesical Bacillus Calmette-Guerin (BCG) or intravesical chemotherapy for non-MIBC; Cohort J: Eligible for pembrolizumab.
- ECOG performance status of 0, 1, or 2.
- Anticipated life expectancy of ≥3 months.
- Tumor samples with an associated pathology report from the diagnostic transurethral resection of a bladder tumor done 90 days prior to the first dose of study treatment must be available prior to enrollment and determined to be sufficient for pathology review and biomarker analysis.
- Participants must be deemed eligible for radical cystectomy and pelvic lymph node dissection.
|
| Critètes d'exclusion |
-
la/mUC - Cohorts A, B, D, E, F, G, and K
- Received any prior treatment with a PD-1 inhibitor, PD-L1 inhibitor, or PD-L2 inhibitor, except Cohort F.
- Received any prior treatment with stimulatory or co-inhibitory T-cell receptor agents, such as CD137 agonists, OX-40 agonists, or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors (except Cohort F).
- Ongoing sensory or motor neuropathy Grade 2 or higher.
- Active central nervous system (CNS) metastases.
- Ongoing clinically significant toxicity (Grade 2 or greater) associated with prior treatment (including radiotherapy or surgery).
- Conditions requiring high doses of steroids or other immunosuppressive medications.
- Prior treatment with enfortumab vedotin or other monomethyl auristatin E (MMAE)-based antibody-drug conjugates (ADCs).
- Uncontrolled diabetes mellitus.
-
MIBC - Cohorts H, J, and L
- Received prior systemic treatment, chemoradiation, and/or radiation therapy of muscle invasive bladder cancer.
- Received any prior treatment with a CPI.
- Received any prior treatment with stimulatory or co-inhibitory T-cell receptor agents, such as CD137 agonists, CTLA-4 inhibitors, or OX-40 agonists.
- Evidence of nodal or metastatic disease on imaging per local assessment. Participants in Cohort L with pT1 disease may not have ≥N2 nodal disease on imaging.
- Ongoing sensory or motor neuropathy Grade 2 or higher.
- Conditions requiring high doses of steroids or other immunosuppressive medications.
- Prior treatment with enfortumab vedotin or other MMAE-based ADCs for urothelial cancer.
- History of another malignancy within 3 years before first dose of study drug.
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Groupe d'étude en oncologie du Québec