This is a multicentre, open label, two-part study to determine whether the focal adhesion kinase (FAK) inhibitor AMP945, when given prior to dosing with gemcitabine and nab-paclitaxel, improves response to therapy in first-line patients with unresectable or metastatic pancreatic cancer. Part A is a phase 1b dose-escalation design that will enrol at least 3 participants in each of 4 dose-level cohorts, to determine the RP2D of AMP945 to be explored in Part B. Part B will determine the efficacy of the AMP945 regimen at the RP2D, and will be run as a Simon Two-stage design; Stage 1 will enrol 26 participants. If ≤5 of the 26 participants show an objective response, then recruitment will be paused and a detailed analysis of futility will be performed. If the study is deemed futile, recruitment will cease. If the study is determined to be not futile or \>5 of the 26 participants show an objective response, recruitment will continue, and an additional 24 participants will be enrolled in Stage 2.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
62
Part A is a phase 1b dose-escalation design that will enrol at least 3 participants in each of 4 dose-level cohorts, to determine the RP2D of AMP945 to be explored in Part B. Dose escalation decisions will be made using a standard 3+3 dose-escalation phase 1 oncology study design.
Part B will determine the efficacy of the AMP945 priming regimen at the recommended phase 2 dose (RP2D) determined in Part A.
GenesisCare
St Leonards, New South Wales, Australia
Calvary Mater Newcastle
Waratah, New South Wales, Australia
Westmead Hospital
Westmead, New South Wales, Australia
Gallipolli Medical Research Foundation
Greenslopes, Queensland, Australia
Epworth Healthcare
Box Hill, Victoria, Australia
Monash Health
Clayton, Victoria, Australia
Epworth Healthcare
Richmond, Victoria, Australia
Western Health
St Albans, Victoria, Australia
National Cancer Centre
Gyeonggi-do, South Korea
Seoul National University Bundang Hospital
Gyeonggi-do, South Korea
...and 3 more locations
Number of Participants with Treatment-Emergent Adverse Events (TEAEs) from Baseline to End of Study
TEAEs during study treatment and follow up periods
Time frame: From first dose of study drug to end of study, an expected average of 6 months
Part A: Determination of RP2D
The RP2D of AMP945 will be determined based on either the maximum tolerated dose or maximum pharmacodynamic effect, which ever is reached first
Time frame: After Cycle 1 (28 days) for each Part A cohort
Part B: efficacy of AMP945
Overall response rate based on RECIST 1.1
Time frame: Imaging every 56 days per participant, with an expected average duration of 6 months
Part A: efficacy of AMP945
Overall response rate based on RECIST 1.1
Time frame: Imaging every 56 days per participant, with an expected average duration of 6 months
AMP945 levels in plasma
Measurement of maximum concentration (cmax) of AMP945
Time frame: Days -8, -7, 1, 3, 4, 8 and 10
AMP945 levels in plasma
Measurement of time to cmax (tmax)
Time frame: Days -8, -7, 1, 3, 4, 8 and 10
AMP945 levels in plasma
Measurement of clearance (CL)
Time frame: Days -8, -7, 1, 3, 4, 8 and 10
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