Outcome
| Type |
Measure |
Description |
Time frame |
Safety issue |
| Primary |
Number of participants with dose limiting toxicities (DLTs) |
DLTs will be evaluated during the first cycle. The number of DLTs will be used to determine the maximum tolerated dose (MTD) |
Baseline through day 28 |
|
| Primary |
Number of participants with treatment emergent adverse events (AEs) |
Adverse events as characterized by type, frequency, severity, timing, seriousness and relationship to study therapy |
Baseline through up to 2 years or until disease progression |
|
| Primary |
Number of participants with laboratory abnormalities |
Laboratory abnormalities as characterized by type, frequency, severity, and timing. |
Baseline through up to 2 years or until disease progression |
|
| Primary |
Objective Response Rate |
Best Overall Response by RECIST 1.1 |
Baseline through up to 2 years or until disease progression |
|
| Secondary |
Pharmacokinetic Parameters: Maximum Observed Plasma Concentration (Cmax) |
Single dose PK will be calculated including Maximum Observed Plasma Concentration (Cmax). |
Cycle 1 Days 1 and 15, predose, 0.5, 1, 2, 4, 6 and 12 hours post dose; predose on Cycle 1 Days 2, 8, 16 and 22 and predose on Day 1 of every Cycle (each cycle is 28 days) thereafter until month 24 |
|
| Secondary |
Pharmacokinetic Parameters: Time to reach Maximum Observed Plasma Concentration (Tmax) |
Single dose PK will be calculated including Time to reach Maximum Observed Plasma Concentration (Tmax). |
Cycle 1 Days 1 and 15, predose, 0.5, 1, 2, 4, 6 and 12 hours post dose; predose on Cycle 1 Days 2, 8, 16 and 22 and predose on Day 1 of every Cycle (each cycle is 28 days) thereafter until month 24 |
|
| Secondary |
Pharmacokinetic Parameters: Area Under the Curve from time 0 to the last sampling time point within the dose interval (AUClast) |
Single dose PK will be calculated including Area Under the Curve from time 0 to the last sampling time point within the dose interval (AUClast) |
Cycle 1 Days 1 and 15, predose, 0.5, 1, 2, 4, 6 and 12 hours post dose; predose on Cycle 1 Days 2, 8, 16 and 22 and predose on Day 1 of every Cycle (each cycle is 28 days) thereafter until month 24 |
|
| Secondary |
Pharmacokinetic Parameters: Terminal elimination half life (t1/2) |
Single dose PK will be calculated including, as data permit, terminal elimination half life (t1/2) |
Cycle 1 Days 1 and 15, predose, 0.5, 1, 2, 4, 6 and 12 hours post dose; predose on Cycle 1 Days 2, 8, 16 and 22 and predose on Day 1 of every Cycle (each cycle is 28 days) thereafter until month 24 |
|
| Secondary |
Pharmacokinetic Parameters: AUC from time 0 extrapolated to infinity (AUCinf) |
Single dose PK will be calculated including, as data permit, Area Under the Curve from time 0 extrapolated to infinity (AUCinf) |
Cycle 1 Days 1 and 15, predose, 0.5, 1, 2, 4, 6 and 12 hours post dose; predose on Cycle 1 Days 2, 8, 16 and 22 and predose on Day 1 of every Cycle (each cycle is 28 days) thereafter until month 24 |
|
| Secondary |
Pharmacokinetic Parameters: Apparent oral plasma clearance (CL/F) |
Single dose PK will be calculated including, as data permit, apparent oral plasma clearance (CL/F) |
Cycle 1 Days 1 and 15, predose, 0.5, 1, 2, 4, 6 and 12 hours post dose; predose on Cycle 1 Days 2, 8, 16 and 22 and predose on Day 1 of every Cycle (each cycle is 28 days) thereafter until month 24 |
|
| Secondary |
Pharmacokinetic Parameters: Apparent volume of distribution (Vz/F) |
Single dose PK will be calculated including, as data permit, apparent volume of distribution (Vz/F) |
Cycle 1 Days 1 and 15, predose, 0.5, 1, 2, 4, 6 and 12 hours post dose; predose on Cycle 1 Days 2, 8, 16 and 22 and predose on Day 1 of every Cycle (each cycle is 28 days) thereafter until month 24 |
|
| Secondary |
Pharmacokinetic Parameters: Maximum Observed Steady State Plasma Concentration (Css,max) |
Multiple dose PK will be calculated including Maximum Observed Steady State Plasma Concentration (Css,max). |
Cycle 1 Days 1 and 15, predose, 0.5, 1, 2, 4, 6 and 12 hours post dose; predose on Cycle 1 Days 2, 8, 16 and 22 and predose on Day 1 of every Cycle (each cycle is 28 days) thereafter until month 24 |
|
| Secondary |
Pharmacokinetic Parameters: Time to reach Maximum Observed Steady State Plasma Concentration (Tss,max) |
Multiple dose PK will be calculated including Time to reach Maximum Observed Steady State Plasma Concentration (Tss,max). |
Cycle 1 Days 1 and 15, predose, 0.5, 1, 2, 4, 6 and 12 hours post dose; predose on Cycle 1 Days 2, 8, 16 and 22 and predose on Day 1 of every Cycle (each cycle is 28 days) thereafter until month 24 |
|
| Secondary |
Pharmacokinetic Parameters: Area Under the Curve within one dose interval (AUCss,t) |
Multiple dose PK will be calculated including Area Under the Curve within one dose interval (AUCss,t) |
Cycle 1 Days 1 and 15, predose, 0.5, 1, 2, 4, 6 and 12 hours post dose; predose on Cycle 1 Days 2, 8, 16 and 22 and predose on Day 1 of every Cycle (each cycle is 28 days) thereafter until month 24 |
|
| Secondary |
Pharmacokinetic Parameters: Steady state apparent oral plasma clearance (CL/F) |
Multiple dose PK will be calculated including, as data permit, steady state apparent oral plasma clearance (CL/F) |
Cycle 1 Days 1 and 15, predose, 0.5, 1, 2, 4, 6 and 12 hours post dose; predose on Cycle 1 Days 2, 8. 16 and 22 and predose on Day 1 of every Cycle (each cycle is 28 days) thereafter until month 24 |
|
| Secondary |
Pharmacokinetic Parameters: Steady state apparent volume of distribution (Vss/F) |
Multiple dose PK will be calculated including, as data permit, steady state apparent volume of distribution (Vss/F) |
Cycle 1 Days 1 and 15, predose, 0.5, 1, 2, 4, 6 and 12 hours post dose; predose on Cycle 1 Days 2, 8, 16 and 22 and predose on Day 1 of every Cycle (each cycle is 28 days) thereafter until month 24 |
|
| Secondary |
Pharmacokinetic Parameters: Accumulation ratio (Rac) |
Multiple dose PK will be calculated including, as data permit, accumulation ratio (Rac) |
Cycle 1 Days 1 and 15, predose, 0.5, 1, 2, 4, 6 and 12 hours post dose; predose on Cycle 1 Days 2, 8, 16 and 22 and predose on Day 1 of every Cycle (each cycle is 28 days) thereafter until month 24 |
|
| Secondary |
Duration of response (DOR) |
DOR as assessed using RECIST 1.1 |
Baseline through up to 2 years or until disease progression |
|
| Secondary |
Progression free survival (PFS) |
PFS as assessed using RECIST 1.1. |
Baseline through up to 2 years or until disease progression |
|
| Secondary |
Time to progression (TTP) |
TTP as assessed using RECIST 1.1. |
Baseline through up to 2 years or until disease progression |
|
| Secondary |
Overall Survival (OS) |
Proportion of participants alive at 6 months, 1 year and 2 years. |
Baseline through up to 2 years |
|
