The purpose of the study was to identify doses and schedules of VOB560 and MIK665 that can be safely given and to learn if the combination can have possible benefits for patients with Non-Hodgkin lymphoma (NHL), Multiple Myeloma (MM) or Acute Myeloid Leukemia (AML). VOB560 and MIK665 are selective and potent blockers respectively of the B-cell lymphoma 2 (BCL2) protein and of the myeloid cell leukaemia 1 (MCL1) protein, proteins that may protect tumor cells from undergoing cell death. VOB560 and MIK665 are designed to block the functions of the BCL2 and MCL1 proteins, so that the tumor cells that rely on these proteins undergo cell death. Preclinical data suggest that concomitant treatment with VOB560 in combination with MIK665 induces robust anti-tumor activity.
This was an open-label, non-randomized multi-center phase Ib dose-escalation study with dose expansion arms in four different patient populations. Patients received VOB560 in combination with MIK665 in a once a week (QW) schedule over 21 days cycle. Less frequent dosing schedules could be explored based on emerging data. Patients were to be treated until disease progression or unacceptable toxicities occurred. The study included a dose escalation part (Part 1) and a dose expansion part (Part 2). The following escalation arms were planned: * Arm A: relapsed/refractory (R/R) NHL and R/R MM * Arm B: R/R AML There were 4 expansion arms planned. However, the expansion part of the study was not initiated.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
37
Uni of TX MD Anderson Cancer Cntr UT MD Anderson Cancer Ctr
Houston, Texas, United States
Novartis Investigative Site
Ghent, Belgium
Novartis Investigative Site
HUS, Finland
Novartis Investigative Site
Hong Kong, Hong Kong
Novartis Investigative Site
Tel Aviv, Israel
Novartis Investigative Site
Rozzano, MI, Italy
Novartis Investigative Site
Sunto Gun, Shizuoka, Japan
Novartis Investigative Site
Seoul, South Korea
Novartis Investigative Site
Santander, Cantabria, Spain
Incidence and severity of AEs and SAEs, including changes in lab values, vital signs, and ECGs
Month 18 is assumed to be study end
Time frame: at month 18
Incidence of Dose Limiting Toxicities (DLTs) during the first cycle of treatment with VOB560 and MIK665 in combination
Month 18 is assumed to be study end
Time frame: at month 18
Frequency of dose interruptions
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
Overall Response Rate (ORR)
Month 18 is assumed to be study end As per European LeukemiaNet (ELN) 2017 for relapse/refractory (R/R) AML As per International Myeloma Working Group (IMWG) 2016 for R/R MM As per Lugano Classification 2014 for R/R NHL
Time frame: at month 18
Complete Response (CR) rate (and rate of CR or sCR in R/R MM)
Month 18 is assumed to be study end As per European LeukemiaNet (ELN) 2017 for relapse/refractory (R/R) AML As per International Myeloma Working Group (IMWG) 2016 for R/R MM As per Lugano Classification 2014 for R/R NHL
Time frame: at month 18
Best Overall Response (BOR)
Month 18 is assumed to be study end As per European LeukemiaNet (ELN) 2017 for relapse/refractory (R/R) AML As per International Myeloma Working Group (IMWG) 2016 for R/R MM As per Lugano Classification 2014 for R/R NHL
Time frame: at month 18
Duration Of Response (DOR)
Month 18 is assumed to be study end Month 18 is assumed to be study end As per European LeukemiaNet (ELN) 2017 for relapse/refractory (R/R) AML As per International Myeloma Working Group (IMWG) 2016 for R/R MM As per Lugano Classification 2014 for R/R NHL
Time frame: at month 18
Progression Free Survival (PFS)
Month 18 is assumed to be study end As per European LeukemiaNet (ELN) 2017 for relapse/refractory (R/R) AML As per International Myeloma Working Group (IMWG) 2016 for R/R MM As per Lugano Classification 2014 for R/R NHL
Time frame: at month 18
Area Under Curve (AUC) of VOB560
PK parameter
Time frame: At the end of Cycle 6 (each cycle is 21 days)
Maximum Plasma Concentration (Cmax) ok VOB560
PK parameter
Time frame: At the end of Cycle 6 (each cycle is 21 days)
Terminal elimination half-life (T1/2) of VOB560
PK parameter
Time frame: At the end of Cycle 6 (each cycle is 21 days)
Clearance (CL) of VOB560
PK parameter
Time frame: At the end of Cycle 6 (each cycle is 21 days)
Apparent volume of distribution (Vz) of VOB560
PK parameter
Time frame: At the end of Cycle 6 (each cycle is 21 days)
Area Under Curve (AUC) of MIK665
PK parameter
Time frame: At the end of Cycle 6 (each cycle is 21 days)
Maximum Plasma Concentration (Cmax) ok MIK665
PK parameter
Time frame: At the end of Cycle 6 (each cycle is 21 days)
Terminal elimination half-life (T1/2) of MIK665
PK parameter
Time frame: At the end of Cycle 6 (each cycle is 21 days)
Clearance (CL) of MIK665
PK parameter
Time frame: At the end of Cycle 6 (each cycle is 21 days)
Apparent volume of distribution (Vz) of MIK665
PK parameter
Time frame: At the end of Cycle 6 (each cycle is 21 days)
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