The purpose of this "first-in-human" study of FAZ053 is to characterize the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and antitumor activity of FAZ053 administered Intravenously (i.v.)as a single agent or in combination with PDR001 in adult patients with advanced solid tumors. By blocking the interaction between Programmed Death Ligand-1 (PD-L1) and its receptors, Programmed Death-1 (PD-1) and B7.1, FAZ053 inhibits the PD-L1 immune checkpoint, resulting in activation of an antitumor immune response by activating effector T-cells and inhibiting regulatory T-cells. This study has been designed as a Phase I, open-label, multi-center study with a dose escalation part of FAZ053 as single agent and in combination with PDR001, followed by a dose expansion part of FAZ053 as single agent. FAZ053 will initially be dosed every three weeks. A less frequent dosing regimen such as every 6 weeks may be evaluated in parallel. A patient may continue treatment with FAZ053 single agent or in combination with PDR001 until the patient experiences unacceptable toxicity, confirmed disease progression per immune related Response Criteria and/or treatment is discontinued at the discretion of the investigator or the patient.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
154
Memorial Sloan Kettering Cancer Ctr
New York, New York, United States
UT MD Anderson Cancer Center
Houston, Texas, United States
Novartis Investigative Site
Toronto, Ontario, Canada
Novartis Investigative Site
Toulouse, France
Novartis Investigative Site
Tel Aviv, Israel
Novartis Investigative Site
Milan, MI, Italy
Novartis Investigative Site
Modena, MO, Italy
Novartis Investigative Site
Koto Ku, Tokyo, Japan
Novartis Investigative Site
Singapore, Singapore
Novartis Investigative Site
Seville, Andalusia, Spain
...and 2 more locations
Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Incidence and severity of AEs and SAEs by treatment group, including changes in vital signs, electrocardiograms (ECGs) and laboratory parameters qualifying and reported as AEs.
Time frame: throughout the study and up to 150 days after end of treatment (up to approximately 46 months)
Incidence of Dose Limiting Toxicities (DLTs)
A DLT is defined as an adverse event or abnormal laboratory value of Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 3 assessed as unrelated to disease, disease progression, inter-current illness or concomitant medications, which occurs within the first 21 days of treatment with FAZ053 alone or within the first 42 days when FAZ053 is given in combination with PDR001 during the dose escalation part of the study. Other clinically significant toxicities may be considered to be DLTs, even if not CTCAE grade 3 or higher.
Time frame: 21 days (single agent FAZ053) and 42 days (FAZ053+PDR001)
Dose interruptions and reductions
Number of participants with dose interruptions and reductions as a measure of tolerability.
Time frame: Up to approximately 41 months
Dose intensity
Dose intensity is defined as actual dose received divided by actual duration of exposure.
Time frame: Up to approximately 41 months
Serum concentration-time profiles of FAZ053 as single agent and FAZ053 in combination with PDR001.
Time frame: 41 months
Presence of anti-FAZ053 and anti-PDR001.
Time frame: 41 months
Concentration of anti-FAZ053 and anti-PDR001.
Time frame: 41 months
Receptor Occupancy (RO) profiles when FAZ053 is given as single agent.
Time frame: 41 months
Total soluble/shed PD-L1 concentration-time profiles when FAZ053 is given as single agent and for FAZ053 in combination with PDR001.
Time frame: 41 months
Histopathology of tumor infiltrating lymphocytes (TILs) by hematoxylin.
Time frame: 41 months
Histopathology of tumor infiltrating lymphocytes (TILs) by eosin (H&E) stain.
Time frame: 41 months
Overall response rate (ORR) per RECIST v1.1
Time frame: 41 months
Best overall response per RECIST v1.1
Time frame: 41 months
Disease control rate per RECIST 1.1
Time frame: 41 months
Progression free survival (PFS) per RECIST 1.1
Time frame: 41 months
Duration of response per RECIST 1.1
Time frame: 41 months
Overall response rate (ORR) per immune related Response Criteria (irRC).
Time frame: 41 months
Progression free survival (PFS) per immune related Response Criteria (irRC).
Time frame: 41 months
Characterization of Tumor Infiltrating Lymphocytes (TILs) by Immunohistochemistry (IHC)
Time frame: 41 months
Characterization of myeloid cell infiltrate by IHC.
Time frame: 41 months
Area under the curve (AUC) for FAZ053 as single agent and FAZ053 in combination with PDR001.
Time frame: 41 months
Cmax for FAZ053 as single agent and FAZ053 in combination with PDR001.
Time frame: 41 months
Tmax for FAZ053 as single agent and FAZ053 in combination with PDR001.
Time frame: 41 months
Half-life for FAZ053 as single agent and FAZ053 in combination with PDR001.
Time frame: 41 months
Clast for FAZ053 as single agent and FAZ053 in combination with PDR001.
Time frame: 41 months
Tlast for FAZ053 as single agent and FAZ053 in combination with PDR001.
Time frame: 41 months
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