The purpose of this study is to evaluate the safety, tolerability and pharmacokinetics of AGS67E both without and with myeloid growth factor (GF) in subjects with refractory or relapsed lymphoid malignancies. Immunogenicity and anticancer activity of AGS67E will also be assessed.
The dose escalation study will have two parts: 1. Dose Escalation of AGS67E without myeloid growth factor (GF) 2. Dose Escalation of AGS67E with myeloid growth factor (GF) Subjects will be enrolled sequentially into dose cohorts starting with AGS67E without GF. All subjects will receive a single 30 minute intravenous (IV) infusion of AGS67E once every three weeks. Subjects will continue treatment until disease progression, intolerability of AGS67E, investigator decision or consent withdrawal. This dose escalation will first determine the maximum tolerated dose (MTD) of AGS67E without GF and then determine the MTD of AGS67E with GF. Once an MTD has been established, the study may enroll subjects into respective expansion cohorts of 12 subjects each at doses recommended by the data review team (DRT) (expansion cohort without GF and/or expansion cohort with GF). During dose escalation, the Data Review Team will review cumulative unaudited data on an interim basis to review subject safety, recommend exploring additional doses and/or schedules, or the expansion of existing cohorts.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
71
intravenous (IV) infusion
Site US0006
Duarte, California, United States
Site US0002
Stanford, California, United States
Site US0004
Fairway, Kansas, United States
Site US0001
New York, New York, United States
Site CA0005
Incidence and nature of adverse events
Time frame: up to 34 months
Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Concentration at the end of infusion (CEOI)
Time frame: Escalation: Days 1-4, 8, 15, 22, 43-46, 50, 64 for Cycles 1-4 and predose once every 3 weeks in subsequent cycles. Expansion: Days 1, 3, 8, 22, 43, 45, 64 in Cycles 1-4 and predose once every 3 weeks in subsequent Cycles up to an average of 4 months
Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Maximum observed concentration (Cmax)
Time frame: Escalation: Days 1-4, 8, 15, 22, 43-46, 50, 64 for Cycles 1-4 and predose once every 3 weeks in subsequent cycles. Expansion: Days 1, 3, 8, 22, 43, 45, 64 in Cycles 1-4 and predose once every 3 weeks in subsequent Cycles up to an average of 4 months
Pharmacokinetic parameter for Monomethyl Auristatin E (MMAE): Time to maximum concentration (Tmax)
Time frame: Escalation: Days 1-4, 8, 15, 22, 43-46, 50, 64 for Cycles 1-4 and predose once every 3 weeks in subsequent cycles. Expansion: Days 1, 3, 8, 22, 43, 45, 64 in Cycles 1-4 and predose once every 3 weeks in subsequent Cycles up to an average of 4 months
Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Partial area under the serum concentration-time curve after first dose and as appropriate (AUC0-21)
Time frame: Escalation: Days 1-4, 8, 15, 22, 43-46, 50, 64 for Cycles 1-4 and predose once every 3 weeks in subsequent cycles. Expansion: Days 1, 3, 8, 22, 43, 45, 64 in Cycles 1-4 and predose once every 3 weeks in subsequent Cycles up to an average of 4 months
Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Terminal or apparent terminal half-life (t1/2)
Time frame: Escalation: Days 1-4, 8, 15, 22, 43-46, 50, 64 for Cycles 1-4 and predose once every 3 weeks in subsequent cycles. Expansion: Days 1, 3, 8, 22, 43, 45, 64 in Cycles 1-4 and predose once every 3 weeks in subsequent Cycles up to an average of 4 months
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Vancouver, British Columbia, Canada
Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Systemic clearance (CL)
Time frame: Escalation: Days 1-4, 8, 15, 22, 43-46, 50, 64 for Cycles 1-4 and predose once every 3 weeks in subsequent cycles. Expansion: Days 1, 3, 8, 22, 43, 45, 64 in Cycles 1-4 and predose once every 3 weeks in subsequent Cycles up to an average of 4 months
Pharmacokinetic parameter for total antibody (TAb), antibody drug conjugate (ADC), and Monomethyl Auristatin E (MMAE): Volume of distribution at steady state (Vss)
Time frame: Escalation: Days 1-4, 8, 15, 22, 43-46, 50, 64 for Cycles 1-4 and predose once every 3 weeks in subsequent cycles. Expansion: Days 1, 3, 8, 22, 43, 45, 64 in Cycles 1-4 and predose once every 3 weeks in subsequent Cycles up to an average of 4 months
Incidence of Anti-Drug Antibody (ADA) formation to the fully human monoclonal antibody (AGS67C) and antibody-drug conjugate (AGS67E)
Time frame: Up to 34 months
Incidence of tumor response
Tumor response is defined as either a complete response (CR) or partial response (PR)
Time frame: Up to 34 months
Objective response rate (ORR)
ORR for a cohort is defined as the percentage of subjects who experience a best response of either complete response (CR) or partial response (PR) in that cohort.
Time frame: Up to 34 months