Outcome
Type |
Measure |
Description |
Time frame |
Safety issue |
Primary |
Maximum Tolerated Dose (MTD) |
Assessed by National Cancer Institute Common Terminology for Adverse Events Criteria (NCI CTCAE v4.03) |
Approximately 6 months |
|
Primary |
Recommended Phase 2 Dose (RP2D) of F1 Formulation In Pediatric Participants Able To Swallow Intact Capsules |
Assessed by NCI CTCAE v4.03 |
Approximately 6 months |
|
Primary |
Recommended Phase 2 Dose (RP2D) of F06 Formulation In Pediatric Participants Able To Swallow Intact Capsules |
Assessed by NCI CTCAE v4.03 |
Approximately 6 months |
|
Primary |
Recommended Phase 2 Dose (RP2D) of F06 Formulation In Pediatric In Participants Dosed Via Feeding Tube (Nasogastric Tube Or Gastric Tube) |
Assessed by NCI CTCAE v4.03 |
Approximately 6 months |
|
Primary |
Recommended Phase 2 Dose (RP2D) Of Minitablets/F15 Formulation In Pediatric Participants Unable To Swallow Intact Capsules |
Assessed by NCI CTCAE v4.03 |
Approximately 6 months |
|
Primary |
Cohort B: Objective Response Rate (ORR) |
Assessed by RANO per the BICR |
Approximately 6 months |
|
Primary |
Cohort D: ORR |
Assessed by RECIST v1.1 per the BICR |
Approximately 6 months |
|
Secondary |
Safety and Tolerability - AE, ECG and Labs assessed by NCI CTCAE v4.03 |
AE, ECG and Labs assessed by NCI CTCAE v4.03 |
Approximately 24 months |
|
Secondary |
Maximum observed plasma drug concentration (Cmax) using F1 Formulation |
Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter |
Approximately 24 months |
|
Secondary |
Maximum observed plasma drug concentration (Cmax) using F06 Formulation given intact |
Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter |
Approximately 24 months |
|
Secondary |
Maximum observed plasma drug concentration (Cmax) using F06 Formulation administered via feeding tube |
Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter |
Approximately 24 months |
|
Secondary |
Maximum observed plasma drug concentration (Cmax) using minitablets/F15 |
Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter |
Approximately 24 months |
|
Secondary |
Time to Cmax, by inspection (Tmax) using F1 Formulation |
Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter |
Approximately 24 months |
|
Secondary |
Time to Cmax, by inspection (Tmax) using F06 Formulation given intact |
Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter |
Approximately 24 months |
|
Secondary |
Time to Cmax, by inspection (Tmax) using F06 Formulation administered via feeding tube |
Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter |
Approximately 24 months |
|
Secondary |
Time to Cmax, by inspection (Tmax) using minitablets/F15 |
Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter |
Approximately 24 months |
|
Secondary |
AUC at steady state (AUCss) using F1 Formulation |
Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter |
Approximately 24 months |
|
Secondary |
AUC at steady state (AUCss) using F06 Formulation given intact |
Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter |
Approximately 24 months |
|
Secondary |
AUC at steady state (AUCss) using F06 Formulation administered via feeding tube |
Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter |
Approximately 24 months |
|
Secondary |
AUC at steady state (AUCss) using minitablets/F15 |
Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter |
Approximately 24 months |
|
Secondary |
Terminal half life (t½) using F1 Formulation |
Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter |
Approximately 24 months |
|
Secondary |
Terminal half life (t½) using F06 Formulation given intact |
Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter |
Approximately 24 months |
|
Secondary |
Terminal half life (t½) using F06 Formulation administered via feeding tube |
Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter |
Approximately 24 months |
|
Secondary |
Terminal half life (t½) using minitablets/F15 |
Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter |
Approximately 24 months |
|
Secondary |
Area under the drug concentration by time curve (AUC) using F1 Formulation |
Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter |
Approximately 24 months |
|
Secondary |
Area under the drug concentration by time curve (AUC) using F06 Formulation given intact |
Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter |
Approximately 24 months |
|
Secondary |
Area under the drug concentration by time curve (AUC) using F06 Formulation administered via feeding tube |
Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter |
Approximately 24 months |
|
Secondary |
Area under the drug concentration by time curve (AUC) using minitablets/F15 |
Assessed by plasma concentrations obtained on Days 1, 2, 8, 15, 22 (Cycle 1), Days 1, 2 (Cycle 2) and on Day 1 of every cycle thereafter |
Approximately 24 months |
|
Secondary |
Cohort A, D, or E: Clinical Benefit Rate (CBR) |
Assessed by RECIST v1.1 per the BICR and investigator |
Approximately 6 months |
|
Secondary |
Cohort B or E: CBR |
Assessed by RANO per the BICR and investigator |
Approximately 6 months |
|
Secondary |
Cohort C: CBR |
Assessed by the Curie scale per the BICR and investigator |
Approximately 6 months |
|
Secondary |
Cohort A, D, or E: Progression-free Survival (PFS) |
Assessed by RECIST v1.1 per the BICR and investigator |
Approximately 6 months |
|
Secondary |
Cohort B or E: PFS |
Assessed by RANO per the BICR and investigator |
Approximately 6 months |
|
Secondary |
Cohort C: PFS |
Assessed by the Curie scale per the BICR and investigator |
Approximately 6 months |
|
Secondary |
Cohort A, D, or E: Overall Survival (OS) |
Assessed by RECIST v1.1 |
Approximately 6 months |
|
Secondary |
Cohort B or E: OS |
Assessed by RANO |
Approximately 6 months |
|
Secondary |
Cohort A, D, or E: ORR |
Assessed by RECIST v1.1 per the BICR and investigator |
Approximately 6 months |
|
Secondary |
Cohort B or E: ORR |
Assessed by RANO per the BICR and investigator |
Approximately 6 months |
|
Secondary |
Cohort C: ORR |
Assessed by the Curie scale per the BICR and investigator |
Approximately 6 months |
|
Secondary |
Cohort A, D, or E: Time to response (TTR) |
Assessed by RECIST v1.1 per the BICR and investigator |
Approximately 6 months |
|
Secondary |
Cohort B or E: TTR |
Assessed by RANO per the BICR and investigator |
Approximately 6 months |
|
Secondary |
Cohort C: TTR |
Assessed by the Curie scale per the BICR and investigator |
Approximately 6 months |
|
Secondary |
Cohort A, D, or E: Duration of Response (DOR) |
Assessed by RECIST v1.1 per the BICR and investigator |
Approximately 6 months |
|
Secondary |
Cohort B or E: DOR |
Assessed by RANO per the BICR and investigator |
Approximately 6 months |
|
Secondary |
Cohort C: DOR |
Assessed by the Curie scale per the BICR and investigator |
Approximately 6 months |
|
Secondary |
Phase 2 Participants with NTRK1/2/3 or ROS1 gene fusions (Cohort B or E): ORR |
Assessed by RANO per the investigator |
Approximately 6 months |
|
Secondary |
Phase 2 Participants with NTRK1/2/3 or ROS1 gene fusions (Cohort D or E): ORR |
Assessed by RECIST v1.1 per the investigator |
Approximately 6 months |
|
Secondary |
Phase 1/2 Participants with NTRK1/2/3 gene fusions (Cohort A, D, or E): ORR |
Assessed by RECIST v1.1 per the BICR and investigator |
Approximately 6 months |
|
Secondary |
Phase 1/2 Participants with NTRK1/2/3 gene fusions (Cohort B or E): ORR |
Assessed by RANO per the BICR and investigator |
Approximately 6 months |
|
Secondary |
Phase 1/2 Participants with ROS1 gene fusions (Cohort A, D, or E): ORR |
Assessed by RECIST v1.1 per the BICR and investigator |
Approximately 6 months |
|
Secondary |
Phase 1/2 Participants with ROS1 gene fusions (Cohort B or E): ORR |
Assessed by RANO per the BICR and investigator |
Approximately 6 months |
|
Secondary |
Phase 1/2 Participants with NTRK1/2/3 or ROS1 gene fusions (Cohort A, D, or E): ORR |
Assessed by RECIST v1.1 per the BICR and investigator |
Approximately 6 months |
|
Secondary |
Phase 1/2 Participants with NTRK1/2/3 or ROS1 gene fusions (Cohort B or E): ORR |
Assessed by RANO per the BICR and investigator |
Approximately 6 months |
|
Secondary |
Phase 2 Participants with NTRK1/2/3 or ROS1 gene fusions (Cohort B or E): DOR |
Assessed by RANO per the BICR and investigator |
Approximately 6 months |
|
Secondary |
Phase 2 Participants with NTRK1/2/3 or ROS1 gene fusions (Cohort D or E): DOR |
Assessed by RECIST v1.1 per the BICR and investigator |
Approximately 6 months |
|
Secondary |
Phase 1/2 Participants with NTRK1/2/3 gene fusions (Cohort A, D, or E): DOR |
Assessed by RECIST v1.1 per the BICR and investigator |
Approximately 6 months |
|
Secondary |
Phase 1/2 Participants with NTRK1/2/3 gene fusions (Cohort B or E): DOR |
Assessed by RANO per the BICR and investigator |
Approximately 6 months |
|
Secondary |
Phase 1/2 Participants with ROS1 gene fusions (Cohort A, D, or E): DOR |
Assessed by RECIST v1.1 per the BICR and investigator |
Approximately 6 months |
|
Secondary |
Phase 1/2 Participants with ROS1 gene fusions (Cohort B or E): DOR |
Assessed by RANO per the BICR and investigator |
Approximately 6 months |
|
Secondary |
Phase 1/2 Participants with NTRK1/2/3 or ROS1 gene fusions (Cohort A, D, or E): DOR |
Assessed by RECIST v1.1 per the BICR and investigator |
Approximately 6 months |
|
Secondary |
Phase 1/2 Participants with NTRK1/2/3 or ROS1 gene fusions (Cohort B or E): DOR |
Assessed by RANO per the BICR and investigator |
Approximately 6 months |
|
Secondary |
Phase 2 Participants with NTRK1/2/3 or ROS1 gene fusions (Cohort B or E): TTR |
Assessed by RANO per the BICR and investigator |
Approximately 6 months |
|
Secondary |
Phase 2 Participants with NTRK1/2/3 or ROS1 gene fusions (Cohort D or E): TTR |
Assessed by RECIST v1.1 per the BICR and investigator |
Approximately 6 months |
|
Secondary |
Phase 1/2 Participants with NTRK1/2/3 gene fusions (Cohort A, D, or E): TTR |
Assessed by RECIST v1.1 per the BICR and investigator |
Approximately 6 months |
|
Secondary |
Phase 1/2 Participants with NTRK1/2/3 gene fusions (Cohort B or E): TTR |
Assessed by RANO per the BICR and investigator |
Approximately 6 months |
|
Secondary |
Phase 1/2 Participants with ROS1 gene fusions (Cohort A, D, or E): TTR |
Assessed by RECIST v1.1 per the BICR and investigator |
Approximately 6 months |
|
Secondary |
Phase 1/2 Participants with ROS1 gene fusions (Cohort B or E): TTR |
Assessed by RANO per the BICR and investigator |
Approximately 6 months |
|
Secondary |
Phase 1/2 Participants with NTRK1/2/3 or ROS1 gene fusions (Cohort A, D, or E): TTR |
Assessed by RECIST v1.1 per the BICR and investigator |
Approximately 6 months |
|
Secondary |
Phase 1/2 Participants with NTRK1/2/3 or ROS1 gene fusions (Cohort B or E): TTR |
Assessed by RANO per the BICR and investigator |
Approximately 6 months |
|