The purpose of this study was to combine the PDR001 checkpoint inhibitor with each of four agents with immunomodulatory activity to identify the doses and schedule for combination therapy and to preliminarily assess the safety, tolerability, pharmacological and clinical activity of these combinations.
This was a Phase Ib, multi-center, open-label study, to characterize the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and antitumor activity of PDR001 in combination with canakinumab, CJM112, trametinib and EGF816 and single agent (s.a.) canakinumab in subjects with Triple Negative Breast Cancer (TNBC), Non-Small Cell Lung Cancer (NSCLC) and Colorectal Cancer (CRC). The study comprised a dose escalation part for combination treatments only, followed by a dose expansion part.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
283
Sidney Kimmel Comprehensive Cancer Center SC-3
Baltimore, Maryland, United States
Frequency of treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) as a measure of safety
Time frame: Throughout the study at every visit, an average of 1 year
Changes between baseline and post-baseline laboratory parameters and vital signs.
Time frame: Baseline and throughout the study at every visit, an average of 1 year
Incidence of dose limiting toxicities (DLTs) of treatment (Escalation only)
Time frame: During the first two cycles; Cycle = 28 days
Frequency of dose interruptions
Time frame: Throughout the study at every visit, an average of 1 year
Dose intensities
Time frame: Throughout the study at every visit, an average of 1 year
Severity of treatment-emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) as a measure of safety
Time frame: Throughout the study at every visit, an average of 1 year
Frequency of dose reductions
Time frame: Throughout the study at every visit, an average of 1 year
Key secondary: Histopathology of tumor infiltrating lymphocytes (TILs)
Time frame: Baseline and approximately after 2 cycles of treatment and at disease progression; Cycle = 28 days
Changes from baseline in electrocardiogram (ECG) parameters
Time frame: Baseline and end of treatment, an average of 1 year
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Tablets
Tablets
Dana Farber Cancer Center
Boston, Massachusetts, United States
Sarah Cannon Research Institute
Nashville, Tennessee, United States
University of Texas MD Anderson Cancer Center
Houston, Texas, United States
Novartis Investigative Site
Brussels, Belgium
Novartis Investigative Site
Wilrijk, Belgium
Novartis Investigative Site
Toronto, Ontario, Canada
Novartis Investigative Site
Montreal, Quebec, Canada
Novartis Investigative Site
Lyon, France
Novartis Investigative Site
Paris, France
...and 13 more locations
Best overall response (BOR)
T1: treatment period 1 (6 cycles of treatment) T2: treatment period 2
Time frame: T1: Every 2 cycles until the start of T2. T2: Every 2 cycles until cycle 3 and then every 3 cycles until PD; cycle = 28 days
Progression free survival (PFS) per irRC and RECIST v1.1
T1: treatment period 1 (6 cycles of treatment) T2: treatment period 2
Time frame: T1: Every 2 cycles until the start of T2. T2: Every 2 cycles until cycle 3 and then every 3 cycles until PD; cycle = 28 days
Treatment Free Survival (TFS)
T1: treatment period 1 (6 cycles of treatment) T2: treatment period 2
Time frame: T1: Every 2 cycles until the start of T2. T2: Every 2 cycles until cycle 3 and then every 3 cycles until PD; cycle = 28 days
Presence and/or concentration of anti-PDR001 antibodies.
T1: treatment period 1 (6 cycles of treatment) T2: treatment period 2
Time frame: Cycle 1 through cycle 6 in treatment period 1 and 2 (an average of 1 year)
Serum concentration of PDR001, canakinumab, CJM112
T1: treatment period 1 (6 cycles of treatment) T2: treatment period 2
Time frame: Cycle 1 through cycle 6 in treatment period 1 and 2 (an average of 1 year)
Plasma concentrations of trametinib and EGF816
T1: treatment period 1 (6 cycles of treatment) T2: treatment period 2
Time frame: Cycle 1 through cycle 6 in treatment period 1 and 2 (an average of 1 year)
Key secondary: Histopathology of myeloid cell infiltrate by IHC (such as CD8, FoxP3 and myeloid markers as appropriate).
Time frame: Baseline and approximately after 3 cycles of treatment and at disease progression; cycle = 28 days
PK parameters (Eg. TMax) of EGF816
T1: treatment period 1 (6 cycles of treatment) T2: treatment period 2
Time frame: Cycle 1 through cycle 6 in treatment period 1 and 2 (an average of 1 year)
PK parameters (Eg. TMax) of trametinib
T1: treatment period 1 (6 cycles of treatment) T2: treatment period 2
Time frame: Cycle 1 through cycle 6 in treatment period 1 and 2 (an average of 1 year)
PK parameter (Eg. TMax) of PDR001
T1: treatment period 1 (6 cycles of treatment) T2: treatment period 2
Time frame: Cycle 1 through cycle 6 in treatment period 1 and 2 (an average of 1 year)
PK parameters (Eg. TMax) of canakinumab
T1: treatment period 1 (6 cycles of treatment) T2: treatment period 2
Time frame: Cycle 1 through cycle 6 in treatment period 1 and 2 (an average of 1 year)
PK parameters (Eg. TMax) of CJM112
T1: treatment period 1 (6 cycles of treatment) T2: treatment period 2
Time frame: Cycle 1 through cycle 6 in treatment period 1 and 2 (an average of 1 year)
Presence and/or concentration of anti-canakinumab antibodies.
T1: treatment period 1 (6 cycles of treatment) T2: treatment period 2
Time frame: Cycle 1 through cycle 6 in treatment period 1 and 2 (an average of 1 year)
Presence and/or concentration of anti-CJM112 antibodies.
T1: treatment period 1 (6 cycles of treatment) T2: treatment period 2
Time frame: Cycle 1 through cycle 6 in treatment period 1 and 2 (an average of 1 year)