This is a Phase 1b/2, multi-center study to assess the safety and efficacy of ibrutinib in combination with durvalumab (MEDI4736) in participants with relapsed or refractory solid tumors.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
124
BTK Inhibitor
Anti PDL-1
Unnamed facility
Birmingham, Alabama, United States
Unnamed facility
Scottsdale, Arizona, United States
Unnamed facility
La Jolla, California, United States
Phase 1b: Number of Participants With Adverse Events as a Measure of Safety and Tolerability of Ibrutinib and Durvalumab (MEDI4736) and to Find the Recommended Phase II Dose.
Time frame: From the date of first study treatment until DLT or disease progression per RECIST 1.1.
Phase 2: Efficacy of Ibrutinib in Combination With Durvalumab (MEDI4736) in Participants With Relapsed or Refractory Solid Tumors by Assessing the ORR Per RECIST 1.1.
Time frame: From the date of first study treatment until progressive disease per RECIST 1.1 or unacceptable toxicity.
Phase 1b/2: Pharmacokinetics (Cmax) of Ibrutinib
Cmax = the peak (maximum) plasma concentration of ibrutinib during the dosing interval on Cycle 3 Day 1.
Time frame: 0hr, 1hr, 2hr, and 4hr post-dose
Phase 1b/2: Pharmacokinetics (AUC0-24h) of Ibrutinib
AUC0-24 = the area under the plasma concentration-time curve of ibrutinib during the dosing interval on Cycle 3 Day 1
Time frame: 0hr, 1hr, 2hr, and 4hr post-dose
Phase 1b/2: Pharmacokinetics (Cmax) of Durvalumab (MEDI4736)
Cmax = the peak (maximum) plasma concentration of durvalumab (MEDI4736) after administration on Cycle 6 Day 1.
Time frame: 60 minutes post-dose (dose administered as an infusion over a 1 hour period)
Phase 1b/2: Pharmacokinetics (Ctrough) of Durvalumab (MEDI4736)
Ctrough = the trough plasma concentration of durvalumab (MEDI4736) after administration on Cycle 6 Day 1
Time frame: Pre-dose
Phase 1b: Pharmacodynamics
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Unnamed facility
Los Angeles, California, United States
Unnamed facility
Los Angeles, California, United States
Unnamed facility
Palo Alto, California, United States
Unnamed facility
San Francisco, California, United States
Unnamed facility
Gainesville, Florida, United States
Unnamed facility
Orlando, Florida, United States
Unnamed facility
Chicago, Illinois, United States
...and 7 more locations
BTK occupancy
Time frame: From the date of first study treatment until DLT or disease progression per RECIST 1.1.
Phase 2: Number of Participants With Adverse Events as a Measure of Safety and Tolerability of Ibrutinib and Durvalumab (MEDI4736)
Time frame: From the date of first study treatment until DLT or disease progression per RECIST 1.1.
Phase 2: Pharmacodynamics
BTK binding site occupancy of ibrutinib was measured from peripheral blood samples collected from participants during Cycle 3 Day 1.
Time frame: Pre-dose