Study BT8009-100 in Subjects With Nectin-4 Expressing Advanced Solid Tumours Malignancies

Official Title

Phase I/II Study of the Safety, Pharmacokinetics, and Preliminary Clinical Activity of BT8009 in Patients With Nectin-4 Expressing Advanced Malignancies

Summary:

This clinical trial is evaluating a drug called BT8009 alone and in combination with nivolumab in participants with advanced solid tumours associated with Nectin-4 expression or in participants with advanced solid tumour malignancies having renal insufficiency. The main goals of this study are to:

• Find the recommended dose of BT8009 that can be given safely to participants alone and in combination with nivolumab
• Learn more about the side effects and effectiveness of BT8009 alone and in combination with nivolumab
• Learn more about BT8009 alone and in combination with nivolumab
• Learn more about BT8009 alone in patients with kidney disease

Trial Description

Primary Outcome:

• Cohorts A-1, A-2 and C: Number of participants with treatment emergent adverse events receiving BT8009 alone and in combination with nivolumab to assess safety and tolerability
• Cohort A-1 and A-2 (escalations): Number of participants with dose limiting toxicities on BT8009 alone and in combination with nivolumab
• Cohort B-1 and B-2 (expansions): Objective response rate (ORR) to assess the clinical activity of BT8009 as a monotherapy and in combination with nivolumab
• Cohort B-1 and B-2 (expansions): Duration of response to assess the clinical activity of BT8009 as a monotherapy and in combination with nivolumab
• Cohort B-1 and B-2 (expansions): Clinical benefit rate to assess the clinical activity of BT8009 as a monotherapy and in combination with nivolumab
• Cohort B-1 and B-2 (expansions): Time to tumour progression to assess the clinical activity of BT8009 as a monotherapy and in combination
• Cohort B-1 and B-2 (expansions): Progression free survival time to assess the clinical activity of BT8009 as a monotherapy and in combination with nivolumab
• Cohort B-1 and B-2 (expansions): Progression free survival rate at 6 months to assess the clinical activity of BT8009 as a monotherapy and in combination with nivolumab using RECIST 1.1
• Cohort B-1 and B-2 (expansions): Overall survival rate at 12 months to assess the clinical activity of BT8009 as a monotherapy and in combination with nivolumab using RECIST 1.1

Secondary Outcome:

• Part A-1 and A-2 and C: Objective response rate to assess preliminary anti-tumour activity of BT8009 as a monotherapy and in combination with nivolumab
• Cohort A-1 and A-2 and C: Duration of Response time to assess preliminary anti-tumour activity of BT8009 as a monotherapy and in combination with nivolumab
• Cohort A-1 and A-2 and C: Clinical benefit rate to assess preliminary anti-tumour activity of BT8009 as a monotherapy and in combination with nivolumab
• Cohort A-1 and A-2 and C: Time to progression to assess preliminary anti-tumour activity of BT8009 as a monotherapy and in combination with nivolumab
• Cohort A-1 and A-2 and C: Progression free survival time to assess preliminary anti-tumour activity of BT8009 as a monotherapy and in combination with nivolumab
• Cohort A-1 and A-2 and C: Progression free survival rate at 6 months to assess preliminary anti-tumour activity of BT8009 as a monotherapy and in combination with nivolumab
• Cohort A-1 and A-2 and C: Overall survival rate to assess preliminary anti-tumour activity of BT8009 as a monotherapy and in combination with nivolumab
• Cohort B1 and B2 (expansion): Number of participants with treatment emergent adverse events receiving BT8009 alone and in combination with nivolumab to assess safety and tolerability
• All cohorts: Plasma concentrations of BT8009 and MMAE to determine its PK parameters
• All cohorts: Number of participants positive for anti-drug antibodies (ADA) to determine incidence of ADA

BT8009 consists of a Bicycle peptide (Bicycle®) which binds selectively to Nectin-4, and is covalently attached to a spacer and a cleavable linker attached to a cytotoxin (MMAE).

This study is a Phase I/II, multicentre, first-in-human, open-label dose-escalation study of BT8009 given as a single agent given once weekly and in combination with nivolumab. There are three parts to this study. Part A is a dose escalation in patients with select advanced solid tumours primarily designed to evaluate safety and tolerability of BT8009 as monotherapy or in combination with nivolumab and to determine a recommended Phase II dose (RP2D). Following a selection of a recommended Phase II dose (RP2D), part B, a dose expansion portion, will be initiated with the primary objective of clinical activity of BT8009 as a monotherapy or in combination with nivolumab in patients with select advanced solid tumours. Part C will evaluate safety and tolerability of chosen RP2D of BT8009 in patients with renal insufficiency.

View this trial on ClinicalTrials.gov