This is a Phase Ib, open label, dose escalation study of spartalizumab + LAG525 in combination with NIR178, capmatinib, MCS110, or canakinumab, followed by a dose expansion in adult patients with advanced or metastatic TNBC. During the dose-escalation part of each treatment arm, patients will be treated with fixed doses of spartalizumab + LAG525 in combination with partner investigational drugs to be escalated until the MTD is reached or a lower RDE is established: NIR178, capmatinib, MCS110, or canakinumab. It is anticipated that other partner study drugs may be added in the future by protocol amendment. After the determination of the MTD/RDE for a particular treatment arm, dose expansion may begin in that arm in order to further assess safety, tolerability, PK/PD, and anti-tumor activity of each combination at the MTD/RDE. Dose expansion arms may initiate only after consideration by the Investigators and Novartis of all available toxicity information, the assessment of risk to future patients from the BLRM, and the available PK, preliminary efficacy, and PD information. There is no requirement for dose-escalation treatment arms reaching an MTD/RDE to proceed to dose expansion.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
64
LIVI (Liquid in vial) Concentrate for Solution for infusion
LAG525 LIVI (Liquid in vial) Concentrate for Solution for infusion
Capsule
Tablet
LIVI (Liquid in vial) Concentrate for Solution for infusion
LIVI (Liquid in vial) Solution for injection
Columbia University Medical Center- New York Presbyterian Columbia
New York, New York, United States
Sarah Cannon Research Institute Sarah Cannon Research
Nashville, Tennessee, United States
Novartis Investigative Site
Westmead, New South Wales, Australia
Novartis Investigative Site
Shatin, New Territories, Hong Kong, Hong Kong
Novartis Investigative Site
Tel Aviv, Israel
Novartis Investigative Site
Milan, MI, Italy
Novartis Investigative Site
Milan, MI, Italy
Novartis Investigative Site
Kashiwa, Chiba, Japan
Novartis Investigative Site
Amsterdam, Netherlands
Novartis Investigative Site
Singapore, Singapore
...and 3 more locations
Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) as a measure of safety
Month 18 is assumed to be study end
Time frame: at month 18
Severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) as a measure of safety
Month 18 is assumed to be study end
Time frame: at month 18
Incidence of dose limiting toxicities (DLTs) of treatment (Escalation only)
end of first cycle
Time frame: at Day 28
Frequency of dose interuptions
Month 18 is assumed to be study end
Time frame: at month 18
Frequency of dose reductions
Month 18 is assumed to be study end
Time frame: at month 18
Dose intensities
Month 18 is assumed to be study end
Time frame: at month 18
Best overall response (BOR)
Month 18 is assumed to be study end
Time frame: at month 18
Progression free survival (PFS) per RECIST v1.1 and iRECIST
Month 18 is assumed to be study end
Time frame: at month 18
Presence of anti-spartalizumab antibodies
Time frame: at Day 1, Day 29, Day 57, Day 85, Day 113, Day 141, Day 197, Day 253, Day 309 and EOT
Presence of anti-LAG525 antibodies
Time frame: at Day 1, Day 29, Day 57, Day 85, Day 113, Day 141, Day 197, Day 253, Day 309 and EOT
Presence of anti-MCS110 antibodies
Time frame: at Day 1, Day 29, Day 57, Day 85, Day 113, Day 141, Day 197, Day 253, Day 309 and EOT
Presence of anti-canakinumab antibodies
Time frame: at Day 1, Day 29, Day 57, Day 85, Day 113, Day 141, Day 197, Day 253, Day 309 and EOT
Serum concentration of spartalizumab, LAG525, MCS110, canakinumab
Time frame: at Day 1, Day 8, Day 15, Day 29, Day 57, Day 65, Day 70, Day 85, Day 113, Day 141, Day 197, Day 253, Day 309 and EOT
Plasma concentration of NIR178, NJI675, capmatinib
Time frame: at Day 1, Day 29, Day 57, Day 85, Day 113, Day 141, Day 197, Day 253, Day 309 and EOT
PK parameter (Tmax) of spartalizumab
cycle 12
Time frame: at month 12
PK parameter (Cmax) of spartalizumab
cycle 12
Time frame: at month 12
PK parameter (AUC) of spartalizumab
cycle 12
Time frame: at month 12
PK parameter (Tmax) of LAG525
cycle 12
Time frame: at month 12
PK parameter (Cmax) of LAG525
cycle 12
Time frame: at month 12
PK parameter (AUC) of LAG525
cycle 12
Time frame: at month 12
PK parameter (Tmax) of NIR178
cycle 12
Time frame: at month 12
PK parameter (Cmax) of NIR178
cycle 12
Time frame: at month 12
PK parameter (AUC) of NIR178
cycle 12
Time frame: at month 12
PK parameter (Tmax) of capmatinib
cycle 12
Time frame: at month 12
PK parameter (Cmax) of capmatinib
cycle 12
Time frame: at month 12
PK parameter (AUC) of capmatinib
cycle 12
Time frame: at month 12
PK parameter (Tmax) of MCS110
cycle 12
Time frame: at month 12
PK parameter (Cmax) of MCS110
cycle 12
Time frame: at month 12
PK parameter (AUC) of MCS110
cycle 12
Time frame: at month 12
PK parameter (Tmax) of canakinumab
cycle 12
Time frame: at month 12
PK parameter (Cmax) of canakinumab
cycle 12
Time frame: at month 12
PK parameter (AUC) of canakinumab
cycle 12
Time frame: at month 12
Changes from baseline of PD markers in tumor tissue (TILs, CD8, PD-L1, LAG-3)
Time frame: at baseline and at Day 43
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