Afatinib Monotherapy in Patients With ERBB-deregulated Metastatic Urothelial Tract Carcinoma After Failure of Platinum Based Chemotherapy

LUX-Bladder 1: Phase II Open Label Single Arm Exploratory Trial of Oral Afatinib Monotherapy Following Platinum Failure for Patients With Advanced/Metastatic Urothelial Tract Carcinoma With Genetic Alterations in ERBB Receptors.

The purpose of this trial is to assess the anti-tumour activity and safety of afatinib monotherapy in patients with urothelial tract carcinoma carrying ERBB2 or ERBB3 (Erythroblastic leukaemia viral oncogene homolog of the human epidermal growth factor family of receptors) mutations or ERBB2 amplifications (Cohort A), and EGFR (Epidermal Growth Factor Receptor) amplification positive tumours (Cohort B), progressing despite previous platinum based chemotherapy, and thereby to improve their prognosis.

The antitumour activity of afatinib monotherapy in these patients will be assessed by progression free survival rate at 6 months (PFS6). This will be the primary endpoint of the trial. A key secondary endpoint will also be defined, the objective response rate (ORR).

Inclusion criteria:

• Recurrent or metastatic urothelial cancer
• Patients must have failed prior platinum based treatment (adjuvant or 1st line)
• Archival tissue sample available for biomarker testing at pre-screening and tissue banking.
• Patients should complete a pre-screening biomarker analysis and should fulfill the following: for Cohort A tumour should show a ERBB2 (epidermal growth factor family receptor 2) or ERBB3 mutation, or ERBB2 gene amplification; for Cohort B tumour should show EGFR (Epidermal Growth Factor Receptor) amplification.
• Further inclusion criteria apply

Exclusion criteria:

• Prior use of EGFR, ERBB2 or ERBB3 targeted treatment
• Chemotherapy within 4 weeks prior to the start of study treatment. Biological therapy or investigational agents within 4 weeks prior to the start of study treatment or prior to passing 5 half-lives, i.e. systemic clearance, whatever comes first
• Known brain metastases or signs hereof, uncontrolled spinal cord compression or leptomeningeal carcinomatosis
• Further exclusion criteria apply