The purpose of this study is to characterize the safety and tolerability of KFA115 and KFA115 in combination with pembrolizumab in patients with select advanced cancers, and to identify the maximum tolerated dose and/or recommended dose.
This is a phase I, open-label, multi-center study of KFA115 as a single agent and in combination with pembrolizumab. The study consists of a dose escalation part, followed by dose expansion part(s) for single-agent KFA115 and KFA115 in combination with pembrolizumab. The escalation parts will characterize safety and tolerability. After the determination of the maximum tolerated dose (MTD) / recommended dose (RD), the dose expansion parts will assess the preliminary anti-tumor activity in defined patient populations and further assess the safety and tolerability at MTD/RD.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
126
Immunomodulatory agent
Anti-PD-1 antibody
Massachusetts General Hospital .
Boston, Massachusetts, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
NYU School of Medicine
New York, New York, United States
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States
SCRI Oncology Partners
Nashville, Tennessee, United States
Novartis Investigative Site
Toronto, Ontario, Canada
Novartis Investigative Site
Guangzhou, Guangdong, China
Novartis Investigative Site
Beijing, China
Novartis Investigative Site
Lyon, France
Novartis Investigative Site
Dresden, Saxony, Germany
...and 9 more locations
Incidence and severity of dose limiting toxicities (DLTs) during the DLT evaluation period of single-agent KFA115 (dose escalation only)
A DLT is defined as an adverse event or abnormal laboratory value that occurs during the DLT evaluation period where the relationship to study treatment cannot be ruled out, and is not primarily related to disease, disease progression, intercurrent illness, or concomitant medications and meets the criteria defined in the study protocol
Time frame: 28 days
Incidence and severity of dose limiting toxicities (DLTs) during the DLT evaluation period of KFA115 in combination with pembrolizumab (dose escalation only)
A DLT is defined as an adverse event or abnormal laboratory value that occurs during the DLT evaluation period where the relationship to study treatment cannot be ruled out, and is not primarily related to disease, disease progression, intercurrent illness, or concomitant medications and meets the criteria defined in the study protocol
Time frame: 28 days
Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)
Incidence and severity of adverse events and serious adverse events, including changes in laboratory values, vital signs, and electrocardiograms qualifying and reported as AEs
Time frame: 35 months
Frequency of dose interruptions, reductions
Number of dose interruptions of KFA115 and pembrolizumab, and number of dose reductions of KFA115
Time frame: 35 months
Dose intensity
Dose intensity of KFA115 and pembrolizumab is defined as the ratio of actual cumulative dose received and actual duration of exposure
Time frame: 35 months
Best overall response (BOR) per RECIST v1.1
BOR is defined as the best response recorded from the start of the treatment until disease progression/recurrence
Time frame: 35 months
Progression free survival (PFS) per RECIST v1.1
PFS is defined as the time from date of start of treatment to the date of event defined as the first documented progression or death due to any cause
Time frame: 35 months
Duration of response (DOR) per RECIST v1.1
DOR is defined as the time from the date of the first documented response (CR or PR) to the date of the first documented progression as per RECIST v1.1 or death due to underlying cancer
Time frame: 35 months
Time to progression (TTP) per RECIST v1.1
TTP is defined as the time from date of start of treatment to the date of event defined as the first documented progression or death due to underlying cancer
Time frame: 35 months
Area under the concentration time curve (AUC) of KFA115 or pembrolizumab
Area under the concentration time curve
Time frame: During the first 168 days of treatment for single-agent KFA115 and 35 months for KFA115 in combination with pembrolizumab
Peak plasma or serum concentration (Cmax) of KFA115 or pembrolizumab
The maximum (peak) observed plasma or serum drug concentration after single dose administration
Time frame: During the first 168 days of treatment for single-agent KFA115 and 35 months for KFA115 in combination with pembrolizumab
Minimum plasma or serum concentration (Cmin) of KFA115 or pembrolizumab
The minimum observed plasma or serum drug concentration reached during the time interval between two dose administrations
Time frame: During the first 168 days of treatment for single-agent KFA115 and 35 months for KFA115 in combination with pembrolizumab
Time to reach peak plasma or serum concentration (Tmax) of KFA115 or pembrolizumab
The time to reach maximum (peak) plasma or serum drug concentration after single dose administration
Time frame: During the first 168 days of treatment for single-agent KFA115 and 35 months for KFA115 in combination with pembrolizumab
Elimination half-life (T1/2) of KFA115 or pembrolizumab
The elimination half-life associated with the terminal slope of a semi logarithmic concentration-time curve
Time frame: During the first 168 days of treatment for single-agent KFA115 and 35 months for KFA115 in combination with pembrolizumab
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