Testing Combination Erdafitinib and Enfortumab Vedotin in Metastatic Bladder Cancer After Treatment With Chemotherapy and Immunotherapy

Titre officiel

Phase Ib Trial of Erdafitinib Combined With Enfortumab Vedotin Following Platinum and PD1/L1 Inhibitors for Metastatic Urothelial Carcinoma With FGFR2/3 Genetic Alterations

Sommaire:

Cet essai de phase Ib évalue la dose optimale, les avantages potentiels et/ou les effets secondaires de l’erdafitinib en association avec l’enfortumab védotine dans le traitement des patients atteints d’un cancer de la vessie qui s’est propagé à d’autres parties de l’organisme (cancer métastatique) et qui présente des modifications génétiques des gènes FGFR2/3. L’erdafitinib appartient à une classe de médicaments appelés inhibiteurs de kinase. Son rôle consiste à bloquer l’action d’une protéine FGFR anormale indiquant aux cellules cancéreuses de se multiplier. Cela peut contribuer à empêcher les cellules cancéreuses de se développer et à les éliminer. L’enfortumab védotine est un anticorps monoclonal, l’enfortumab, lié à un agent anticancéreux appelé védotine. L’enfortumab se fixe de manière ciblée à une protéine, appelée protéine nectine-4, sur les cellules cancéreuses, et libère la védotine pour détruire ces cellules. Il s’agit d’un type de conjugué anticorps-médicament. L’administration d’erdafitinib en association avec l’enfortumab védotine peut réduire ou stabiliser le cancer de la vessie métastatique présentant des modifications des gènes FGFR 2/3.

Description de l'essai

Primary Outcome:

• Incidence of adverse events
• Recommended phase II dose
• Maximum tolerated dose of enfortumab vedotin

Secondary Outcome:

• Overall response rate
• Duration of response
• Progression free survival
• Overall survival

Primary Objectives:

• To determine the feasibility and safety of erdafitinib when combined with enfortumab vedotin (EV) for patients with metastatic urothelial carcinoma (mUC) harboring FGFR2/3 activating genomic alterations who are progressing following platinum-based chemotherapy and PD1/L1 inhibitors.
• To determine the maximally tolerated dose (MTD) and the recommended phase 2 dose (RP2D) of EV when combined with erdafitinib.

Secondary Objectives:

• To observe and record anti-tumour activity.
• To observe and record overall response rate (ORR).
• To observe and record duration of response (DOR).
• To observe and record progression-free survival (PFS).
• To observe and record overall survival (OS).

Exploratory Objectives:

• Assess association of tumour PD-L1 and nectin-4 protein expression with response.
• Use commercial tissue next generation sequencing (NGS) assay to confirm FGFR status as well as to describe the genomic landscape of metastatic UC.
• Assess genomic changes by circulating tumour (ct)-deoxyribonucleic acid (DNA) assessment to study mechanisms of resistance with treatment.
• Assess pharmacokinetic (PK) of monomethyl auristatin E (MMAE) and erdafitinib.

Outline:
This is a dose-escalation study of enfortumab vedotin in combination with fixed dose erdafitinib followed by a dose-expansion study of the drug combination. Patients receive erdafitinib orally (PO) once daily (QD) on days 1-28 and enfortumab vedotin intravenously (IV) over 30 minutes on days 1, 8, and 15 of each cycle. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for up to 2 years.

Voir cet essai sur ClinicalTrials.gov