This is a Phase 1, open-label, dose-escalation, and dose-expansion, with a gated randomization portion, study to evaluate the safety, tolerability, pharmacokinetic, pharmacodynamic and clinical activity of AB680 in combination with zimberelimab (AB122), nab-paclitaxel and gemcitabine in participants with advanced pancreatic cancer.
Dose escalation of AB680 in combination with zimberelimab (AB122), nab-paclitaxel and gemcitabine will be assessed in participants with advanced pancreatic cancer. In this dose escalation combination study, participants with advanced pancreatic cancer will receive escalating doses of AB680 in combination with zimberelimab at the recommended phase 2 dose (RP2D), and nab-paclitaxel and gemcitabine at standard doses. AB680, zimberelimab, nab-paclitaxel and gemcitabine are all administered via IV infusion. In the dose expansion portion of the study in front-line (1L) pancreatic patients, participants will receive AB680 at the RP2D determined from the dose escalation study in combination with zimberelimab at the RP2D and nab-paclitaxel and gemcitabine at standard doses or AB680 at the RP2D in combination with nab-paclitaxel and gemcitabine at standard doses. In the dose-expansion portion of the study in second-line (2L) pancreatic patients, participants will receive AB680 at the RP2D determined from the dose-escalation study in combination with zimberelimab at the RP2D and nab-paclitaxel and gemcitabine at standard doses.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
196
AB680 is a Cluster of Differentiation (CD)73 Inhibitor.
Zimberelimab is a fully human immunoglobulin G4 (IgG4) monoclonal antibody targeting human PD-1.
Nab-paclitaxel is a chemotherapy agent. Chemotherapy agents are medicines that kill cancer cells.
Research Site
Santa Monica, California, United States
Research Site
St Louis, Missouri, United States
Research Site
New York, New York, United States
Research Site
New York, New York, United States
Number of participants with Treatment Emergent Adverse Events (TEAEs)
Safety will be assessed by monitoring adverse events and clinically relevant changes in 12 lead Electrocardiogram (ECG) and Physical examination findings
Time frame: From first dose date to 90 days after the last dose (approximately 1 year)
Number of Participants With Dose Limiting Toxicities
Time frame: From First dose to day 28
Duration of response
Time at which response criteria are met for complete response or partial response (whichever occurs first) until the first date of recurrence, progression or death per RECIST v1.1
Time frame: Start date of response to first progression/death, up to 1 year
Disease control rate
Number of participants with complete response, partial response, or stable disease for greater than 6 months per RECIST v1.1
Time frame: First dose date to first progression/death
Overall survival
Overall survival rate, defined as time between first dose date and date of death
Time frame: First dose date to date of death, up to 1 year
Progression free survival
Number of participants without disease progression per RECIST v1.1
Time frame: First dose date to first progression/death
AB680 peak plasma concentration (Cmax)
Peak plasma concentration (Cmax) of AB680
Time frame: Day 1 (sequential), day 2, day 3, day 8, day 15, day 29, day 36, day 43, day 57, day 85, day 197, day 309, day 421, 30 days after last dose, and 90 days after last dose
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Gemcitabine is a chemotherapy agent. Chemotherapy agents are medicines that kill cancer cells.
Research Site
Philadelphia, Pennsylvania, United States
Research Site
Pittsburgh, Pennsylvania, United States
Research Site
Houston, Texas, United States
Research Site
San Antonio, Texas, United States
Research Site
Madison, Wisconsin, United States
Zimberelimab peak plasma concentration (Cmax)
Peak plasma concentration (Cmax) of zimberelimab
Time frame: Day 1 (sequential), day 2, day 3, day 8, day 15, day 29, day 43, day 57, day 85, day 197, day 309, day 421, 30 days after last dose, and 90 days after last dose
AB680 time of peak concentration (Tmax)
Time of peak concentration (Tmax) of AB680
Time frame: Day 1 (sequential), day 2, day 3, day 8, day 15, day 29, day 36, day 43, day 57, day 85, day 197, day 309, day 421, 30 days after last dose, and 90 days after last dose
Zimberelimab time of peak concentration (Tmax)
Time of peak concentration of zimberelimab
Time frame: Day 1 (sequential), day 2, day 3, day 8, day 15, day 29, day 43, day 57, day 85, day 197, day 309, day 421, 30 days after last dose, and 90 days after last dose
AB680 area under the plasma concentration versus time curve (AUC)
Area under the plasma concentration versus time curve (AUC) of AB680
Time frame: Day 1 (sequential), day 2, day 3, day 8, day 15, day 29, day 36, day 43, day 57, day 85, day 197, day 309, day 421, 30 days after last dose, and 90 days after last dose
Zimberelimab area under the plasma concentration versus time curve (AUC)
Area under the plasma concentration versus time curve (AUC) of zimberelimab
Time frame: Day 1 (sequential), day 2, day 3, day 8, day 15, day 29, day 43, day 57, day 85, day 197, day 309, day 421, 30 days after last dose, and 90 days after last dose
Immunogenicity indicators: anti-drug antibodies (ADA)
Number of participants who develop anti-drug antibodies to zimberelimab
Time frame: Day 1, day 15, day 29, day 57, day 85, day 197, day 309, and day 421
Overall response rate
Number of Participants with Complete or Partial Response per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v.1.1
Time frame: First dose date to progression or last tumor assessment, up to 1 year