The primary goal of this Phase 1 study is to characterize the safety and tolerability of tebotelimab and establish the maximum tolerated dose (MTD) of tebotelimab in advanced solid tumors, and tebotelimab in combination with margetuximab in HER2+ advanced solid tumors. Pharmacokinetics (PK), immunogenicity, pharmacodynamics (PD), and the anti-tumor activity of tebotelimab will also be assessed.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
277
1 mg IV every other week
3 mg IV every other week
10 mg IV every other week
30 mg IV every other week
120 mg IV every other week
300 mg IV every other wee
400 mg IV every other wee
600 mg IV every other week
800 mg IV every other week
1200 mg IV every other week
15 mg/kg IV every 3 weeks
Banner MD Anderson Cancer Center
Gilbert, Arizona, United States
USC/Norris Comprehensive Cancer Center
Los Angeles, California, United States
UCLA Hematology & Oncology Clinic
Los Angeles, California, United States
Hoag Memorial Hospital Presbyterian
Newport Beach, California, United States
Florida Cancer Specialists & Research Institute
Sarasota, Florida, United States
Number of participants with Treatment-Emergent Adverse Events (TEAE) as assessed by CTCAE v4.03 (tebotelimab monotherapy)
Safety Safety is based on evaluation of adverse events (AEs) and serious adverse events (SAEs) from the time of study drug administration through the End of Study visit.
Time frame: up to 24 months
Number of participants with Treatment-Emergent Adverse Events as assessed by CTCAE v4.03 (tebotelimab plus margetuximab)
Safety
Time frame: up to 24 months
Area Under the Plasma Concentration versus Time Curve (AUC) of tebotelimab
AUC
Time frame: From Day 1 to Day 15 after the first and second doses
Maximum Plasma Concentration (Cmax) of tebotelimab and tebotelimab plus margetuximab
Cmax
Time frame: At the end of infusion on Study Days 1, 15, 29 and 43 in Cycles 1 and 2 and on Study Day 1 for all subsequent cycles until treatment discontinuation, up to 2 years
Time to reach maximum (peak) plasma concentration (Tmax) of tebotelimab and tebotelimab plus margetuximab
Tmax
Time frame: At the end of infusion on Study Days 1, 15, 29 and 43 in Cycles 1 and 2 and on Study Day 1 for all subsequent cycles until treatment discontinuation, up to 2 years
Trough plasma concentration (Ctrough) of tebotelimab
Ctrough
Time frame: Study Days 1, 15, 29, 43 in Cycles 1 and 2 and Day 1 of each subsequent cycle s until treatment discontinuation, up to 2 years
Total body clearance of the drug from plasma (CL) of tebotelimab
CL
Time frame: Cycle 1 Day 1 out to Cycle 1 Day 15
Apparent volume of distribution at steady state (Vss) of tebotelimab
Vss
Time frame: Cycle 1 Day 1 out to Cycle 1 Day 15
Terminal half-life (t1/2) of tebotelimab
t1/2
Time frame: Cycle 1 Day 1 out to Cycle 1 Day 15
Number of patients with anti-drug antibody
immunogenicity
Time frame: Study Day 1, 15, 29, 57, 85, 113, then every 56 days up to 2 years Tebotelimab plus margetuximab: Day 1, 22, 43, and then every 6 weeks until treatment discontinuation
Objective response rate (ORR)
ORR is the percentage of participants who have a complete response or a partial response to treatment.
Time frame: Throughout the study, up to 4 years.
Median Duration of response (DoR)
DoR is defined as the time from the date of initial response (CR or PR) to the date of first documented PD or death from any cause, whichever occurs first. Median DoR is the time when 50% of responders are still in response.
Time frame: Throughout the study, up to 4 years.
Progression-free survival (PFS)
PFS is defined as the time from the first dose date to the date of first documented PD or death from any cause, whichever occurs first. Median PFS is the time when 50% of participants remain free of PD or death.
Time frame: Throughout the study, up to 4 years.
Median Overall survival (OS)
OS is defined as the time from the first dose date to the date of death from any cause. Median OS is the time when 50% of participants are still alive.
Time frame: Throughout the study, up to 4 years.
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University of Chicago Medicine
Chicago, Illinois, United States
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States
Massachusetts General Hospital and Dana-Farber Cancer Institute
Boston, Massachusetts, United States
Duke University Medical Center
Durham, North Carolina, United States
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States
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