Enfortumab Vedotin With or Without Pembrolizumab in Rare Genitourinary Tumors (E-VIRTUE) : A Phase II Multicenter Study of Enfortumab Vedotin With or Without Pembrolizumab in Rare Genitourinary Tumors (E-VIRTUE)

Background:Rare genitourinary (GU) tumors are tumors of aberrant histology occurring in the GU tract including kidney, unrinary tract, ureters, testes, and penis. Due to their rarity, they are not systematically captured by currently available registries, treatment protocols or tissue banks.Large randomized clinical trials are logistically difficult in these small patient populations. Therefore, treatment information is obtained from case reports, retrospective studies, and small clinical trials, and is frequently extrapolated from trials on similar tumor types.Pembrolizumab is a potent and highly selective humanized monoclonal antibody that targets immune checkpoint programmed cell death protein 1 (PD-1) receptor.Nectin-4 is a type 1 transmembrane protein and member of a family of related immunoglobulinlike adhesion molecules implicated in cell-cell adhesion.Nectin-4 is highly expressed in cancer cells, particularly in urothelial carcinomas (UCs).Enfortumab vedotin (EV) is an antibody-drug conjugate consisting of a human monoclonal antibody to nectin-4 and monomethyl auristatin E (MMAE), a microtubule disrupting cytotoxic agent. EV has demonstrated a survival benefit in the setting of metastatic urothelial carcinoma, which has almost universally high nectin-4 expression.There is data in UC and unrinary tract cancer variants showing co-existence of nectin-4 expression and programmed cell death 1 ligand 1 (PD-L1) expression and mismatch repair deficiency.There is currently very limited data on the level of nectin-4 expression in rare GU tumors and no evidence for the activity of EV in these tumors.Objective:-To assess the objective response rate (ORR) per RECIST v 1.1 in participants with rare genitourinary (GU) tumors treated with enfortumab vedotin (EV) with or without pembrolizumab.Eligibility:Age >= 18 yearsHistologically confirmed diagnosis of locally advanced or metastatic pure adenocarcinoma of the unrinary tract, pure squamous cell carcinoma of the unrinary tract, or treatment-refractory testicular germ cell tumors.Participants may have received any number of prior anti-cancer treatments or be treatment na(SqrRoot) ve (with the exception of participants with testicular germ cell tumors, whom must have exhausted all standard curative-intent options).Design:This multisite study is a phase II, open label, multicohort, nonrandomized study with two arms.Participants with:Adenocarcinoma of the unrinary tract will be enrolled in Cohort A (Cohort A1: prior anti-1/PD-L1 therapy; Cohort A2: no prior anti-PD-1/PD-L1 therapy).Squamous cell carcinoma of the unrinary tract will be enrolled in Cohort B (Cohort B1: prior anti-PD-1/PD-L1 therapy; Cohort B2: no prior anti-PD-1/PD-L1 therapy).Testicular germ cell tumors will be enrolled in Cohort C (Cohort C1: prior anti-PD-1/PDL1 therapy; Cohort C2: no prior anti-PD-1/PD-L1 therapy).All participants will receive EV.Participants without prior immune checkpoint inhibitor (ICI) exposure will be eligible to receive concurrent pembrolizumab.Arm 1: EV monotherapy will be given in 28-day cycles for a maximum of 5 years, or until disease progression or intolerable side effects. EV will be administered I.V. at 1.25 mg/kg on days 1, 8, and 15 of each cycle.Arm 2: EV and pembrolizumab will be given in 21-day cycles. EV will be administered I.V. at 1.25 mg/kg on days 1 and 8 of each cycle. Pembrolizumab will be administered I.V. at 200 mg on day 1.EV and pembrolizumab will be given for 35 cycles, or until a confirmed complete response, disease progression or intolerable side effects.After the 35th cycle, EV may be continued to be given for a maximum of 5 years, or until disease progression or intolerable side effects.Participants who have completed 35 cycles of pembrolizumab or stopped pembrolizumab for confirmed complete response may be eligible for up to additional 17 cycles of pembrolizumab if there is investigator-determined progressive disease by RECIST 1.1 after initial treatment.The accrual ceiling will be set at 68 participants to allow for inevaluable participants..

Medienart:	Klinische Studie

Erscheinungsjahr:	2024
Erschienen:	2024

Enthalten in:	ClinicalTrials.gov - (2024) vom: 02. Apr. Zur Gesamtaufnahme - year:2024

Sprache:	Englisch

Links:	Volltext [kostenfrei]

Themen:	610 Neoplasms, Germ Cell and Embryonal Phase: Phase 2 Recruitment Status: Not yet recruiting Study Type: Interventional Urinary Bladder Neoplasms

Anmerkungen:	Source: Link to the current ClinicalTrials.gov record., First posted: September 18, 2023, Last downloaded: ClinicalTrials.gov processed this data on April 03, 2024, Last updated: April 03, 2024

Study ID:	NCT06041503 10001533 001533-C
Veröffentlichungen zur Studie:

fisyears:
Förderinstitution / Projekttitel:

PPN (Katalog-ID):	CTG000015040