This multi-center, open-label study will evaluate the safety, pharmacokinetics, pharmacodynamics and preliminary efficacy of vanucizumab as a single agent or in combination with atezolizumab in participants with locally advanced or metastatic solid tumors. Cohorts of participants will receive escalating doses of vanucizumab, fixed dose of vanucizumab (MTD and/or recommended phase two dose \[RP2D\]), and fixed dose of vanucizumab in combination with atezolizumab, intravenously every 2 weeks.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
132
Participants will receive atezolizumab at a fixed dose of 840 mg, intravenously every 2 weeks.
Participants will receive escalating doses of vanucizumab (starting dose: 3 milligram \[mg\] per kilogram) and fixed dose of vanucizumab (MTD/RP2D: 30 mg/kg), intravenously every 2 weeks.
Cliniques Universitaires St-Luc
Brussels, Belgium
UZ Leuven Gasthuisberg
Leuven, Belgium
Institut Bergonie; Oncologie
Bordeaux, France
Maximum Tolerated Dose (MTD) of Vanucizumab
Time frame: approximately 28 days
Number of Participants With Objective Response According to RECIST 1.1 Criteria
Time frame: approximately 3 years
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: approximately 3 years
Number of Participants With Dose-limiting Toxicities (DLTs)
Time frame: approximately 28 days
Elimination Half-life (t1/2) of Vanucizumab
Time frame: Cycle 1 & 4: 0 hour (pre-dose), end of infusion (maximum up to 120 minutes); Cycle 2, 3, 8, every 8 weeks after cycle 8: 0 hour (pre-dose)
Area Under the Plasma Concentration-time Curve During one Dosing Interval (AUCtau) of Vanucizumab
Time frame: Cycle 1 & 4: 0 hour (pre-dose), end of infusion (maximum up to 120 minutes); Cycle 2, 3, 8, every 8 weeks after cycle 8: 0 hour (pre-dose)
Clearance of Study Drug From the Body (CL)
Time frame: Cycle 1 & 4: 0 hour (pre-dose), end of infusion (maximum up to 120 minutes); Cycle 2, 3, 8, every 8 weeks after cycle 8: 0 hour (pre-dose)
Volume of Distribution at Steady-State (Vss) of Vanucizumab
Time frame: Cycle 1 & 4: 0 hour (pre-dose), end of infusion (maximum up to 120 minutes); Cycle 2, 3, 8, every 8 weeks after cycle 8: 0 hour (pre-dose)
Accumulation Ratio (RA) of Vanucizumab
Time frame: Cycle 1 & 4: 0 hour (pre-dose), end of infusion (maximum up to 120 minutes); Cycle 2, 3, 8, every 8 weeks after cycle 8: 0 hour (pre-dose)
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Centre Francois Baclesse; Oncologie
Caen, France
Centre Leon Berard; Departement Oncologie Medicale
Lyon, France
Institut Curie; Oncologie Medicale
Paris, France
ICO - Site René Gauducheau
Saint-Herblain, France
Institut Gustave Roussy; Sitep
Villejuif, France
Clinica Universitaria de Navarra; Servicio de Oncologia
Pamplona, Navarre, Spain
Hospital del Mar; Servicio de Oncologia
Barcelona, Spain
...and 4 more locations
Number of Participants With Objective Response According to RECIST 1.1 Criteria, CA-125 Response Criteria, and Immune-modified RECIST Criteria
Time frame: approximately 3 years
Number of Participants With Disease Control According to RECIST 1.1 Criteria
Time frame: approximately 3 years
Progression Free Survival (PFS) According to RECIST 1.1 Criteria
Time frame: Baseline until disease progression or death (up to approximately 3 years)
Biological Progression-free Interval (PFIbio) According to RECIST 1.1 Criteria
Time frame: Baseline until biologic progression or death (up to approximately 3 years)
Overall Survival (OS)
Time frame: Baseline until death (up to approximately 3 years)
Change From Baseline in Micro Vessel Density (MVD) Assessed by Paired Tumor Biopsies
Time frame: approximately 2 years
Change From Baseline in Proliferation and Apoptosis of Endothelial cells and Tumor Cells Assessed by Paired Tumor Biopsies
Time frame: approximately 2 years
Change From Baseline in Maturity of Blood Vessels Assessed by Paired Tumor Biopsies
Time frame: approximately 2 years
Change From Baseline in Targets and Receptors Assessed by Paired Tumor Biopsies
Time frame: approximately 2 years
Change From Baseline in Blood Plasma Volume (Vp), Extracellular Extravascular Space Volume (Ve), and Volume Transfer Coefficient, Assessed by Bio-Imaging
Time frame: approximately 2 years
Change From Baseline in Apparent Diffusion Coefficient (ADC) Assessed by Bio-Imaging
Time frame: approximately 2 years
Percentage of Participants With Human Anti-Human Antibodies (HAHA) to Vanucizumab and Atezolizumab (ATA)
Time frame: 0 hours (pre-dose) in Part I, II, and III (Cycle 1, 5, 6, end of study [EoS] visit) Part IV (Cycle 1, 3, 4, 8, every 8 weeks after cycle 8, EoS visit)
Area under the Concentration-time Curve (AUC) of Vanucizumab
Time frame: Cycle 1 & 4: 0 hour (pre-dose), end of infusion (maximum up to 120 minutes); Cycle 2, 3, 8, every 8 weeks after cycle 8: 0 hour (pre-dose)
Maximum Observed Plasma Concentration (Cmax) of Vanucizumab
Time frame: Cycle 1 & 4: 0 hour (pre-dose), end of infusion (maximum up to 120 minutes); Cycle 2, 3, 8, every 8 weeks after cycle 8: 0 hour (pre-dose)
Minimum Observed Plasma Concentration (Cmin) of Vanucizumab
Time frame: Cycle 1 & 4: 0 hour (pre-dose); Cycle 2, 3, 8, every 8 weeks after cycle 8: 0 hour (pre-dose)
Time of Observed Maximum Plasma Concentration (Tmax)
Time frame: Cycle 1 & 4: 0 hour (pre-dose), end of infusion (maximum up to 120 minutes); Cycle 2, 3, 8, every 8 weeks after cycle 8: 0 hour (pre-dose)