Neoplasms
Conditions
Keywords
Solid tumors
Brief summary
To evaluate the safety and tolerability of oral SKI-606 (bosutinib) administered on a daily schedule to subjects with advanced malignant solid tumors and to define a maximum tolerated dose (MTD) in this subject population.
Interventions
DRUGbosutinib
Dose levels evaluated 50mg, 100mg, 200mg, 300mg, 400mg, 500mg and 600mg. 500mg was identified as MTD, however due to GI toxicities at that dose, 400mg was selected as the RP2D. Drug was administered as long as tolerable and disease under study did not worsen.
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Advanced or recurrent solid malignancy confirmed histologically or cytologically for which no effective therapy is available. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1. * Measurable disease as outlined by the modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria. * Other inclusion applies.
Exclusion criteria
* Use of any systemic antitumor agents or any investigational agent within 28 days before the first dose of test article is administered. * Prior exposure to SKI-606 or any other Src-kinase inhibitor, major surgery or radiotherapy within 14 days before the first dose of test article (recovery from previous surgery should be complete before day 1). * Active central nervous system (CNS) metastases, as indicated by clinical symptoms, cerebral edema, requirement for corticosteroids and/or progressive growth (Treated CNS metastases must be stable for \>= 2 weeks before day 1). * Other exclusion applies.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose (MTD) in Part 1 | Part 1 Day 1 up to Day 28 | MTD: highest dose level at which not more than 1 of 6 participants experienced DLT after 21 days of treatment (Cycle 1). DLT included any grade 3 or 4 clinically-evident non-hematologic toxicity, grade 4 neutropenia of \>= 7-day duration or with fever \>= 38.5 degrees Celsius (febrile neutropenia); grade 4 thrombocytopenia \>= 2-day duration or with bleeding requiring platelet transfusion, any clinically-significant grade \>= 2 toxicity that requires \>=14 days to resolve (to =\< grade 1) which occurred in first 21 days of study and considered at least possibly related to bosutinib. |
| Number of Participants With Dose-limiting Toxicities (DLT) in Part 1 | Part 1 Baseline up to Day 28 | DLT included any grade 3 or 4 clinically-evident non-hematologic toxicity, grade 4 neutropenia of greater than or equal to (\>=) 7-day duration or with fever \>= 38.5 degrees Celsius (febrile neutropenia); grade 4 thrombocytopenia \>= 2-day duration or with bleeding requiring platelet transfusion, any clinically-significant grade \>= 2 toxicity that requires \>=14 days to resolve (to less than or equal to \[=\<\] grade 1) which occurred in first 21 days of study and considered at least possibly related to bosutinib. |
| Number of Participants With Adverse Events (AEs) by Seriousness | Baseline up to 30 days after last dose | Counts of participants who had treatment-emergent adverse events (TEAEs), defined as newly occurring or worsening after first dose. Participants with multiple occurrences of an AE within a category were counted once within the category. |
| Duration of Most Frequently Observed Adverse Events (AEs) | Baseline up to 30 days after last dose | The most frequently observed treatment-emergent AEs were gastrointestinal disorders which included diarrhea, nausea and vomiting. Duration of AE per event is calculated as AE stop date minus AE start date plus 1. |
| Number of Participants With Best Overall Response (BOR) in Part 1 | Part 1 Baseline, last week (Day 15 to 23) of cycles 2, 4, 6, 8 and thereafter every 3 cycles up to 30 days after last dose | BOR:investigator assessment by modified Response Evaluation Criteria in Solid Tumors (RECIST), recorded from treatment start until disease progression/recurrence. Complete Response:disappearance of all lesions. Partial Response (PR):\>=30% decrease in sum of longest diameters (SLDs) of target lesions (TLs) taking as reference baseline SLD. Progressive disease (PD):\>=20% increase in SLD of TLs taking as reference smallest SLD since treatment start, or appearance of \>=1 new lesion. Stable disease: neither shrinkage for PR nor increase for PD taking as reference smallest SLD since treatment start. |
| Number of Participants With Best Overall Response (BOR) in Part 2 | Part 2 Baseline, last week (Day 15 to 23) of cycles 2, 4, 6, 8 and thereafter every 3 cycles up to 30 days after last dose | BOR: investigator assessment by modified RECIST, recorded from treatment start until disease progression/recurrence. Complete Response: disappearance of all lesions. PR: \>=30% decrease in SLDs of TLs taking as reference baseline SLD. PD: \>=20% increase in SLD of TLs taking as reference smallest SLD since treatment start, or appearance of \>=1 new lesion. Stable disease: neither shrinkage for PR nor increase for PD taking as reference smallest SLD since treatment start. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Change From Baseline in Physical Examination | Baseline up to end of treatment (Week 95) | Physical examinations included body weight, height and vital signs and only finding that exceeded the criterion for PCS was weight. Criteria for weight was: an increase or decrease of \>=10% from baseline. |
| Number of Participants With Change From Baseline in Opthalmologic Examination | Baseline up to end of treatment (Week 95) | Ophthalmologic evaluation included visual acuity, funduscopic examination, and any clinically-significant abnormality. |
| Overall Survival (OS) in Part 2 | Part 2 Baseline until death or 3, 6, 9 and 12 months after treatment discontinuation | Time in weeks from the start of study treatment to date of death due to any cause. OS was calculated as (the death date minus the date of first dose of study medication plus 1) divided by 7. Death was determined from death case report forms (CRFs) or from follow-up contact data (where the participant current status was death). |
| Progression Free Survival (PFS) in Part 2 | Part 2 Baseline until death or 3, 6, 9 and 12 months after treatment discontinuation | Time in weeks from start of study treatment to first documentation of objective tumor progression or death due to any cause. PFS was calculated as (first event date minus the date of first dose of study medication plus 1) divided by 7. Tumor progression was determined from oncologic assessment data (where data meet the criteria for PD, or from death CRFs). |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) | 0 hour (pre-dose) on Day 1, 0 (pre-dose), 1, 2, 3, 4, 6, 8, 24 (0 hour [pre-dose] on Day 15) hours post-dose on Day 14 | — |
| Plasma Decay Half-Life (t1/2) | 0 hour (pre-dose) on Day 1, 0 (pre-dose), 1, 2, 3, 4, 6, 8, 24 (0 hour [pre-dose] on Day 15) hours post-dose on Day 14 | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. |
| Area Under the Concentration-Time Curve (AUC) | 0 hour (pre-dose) on Day 1, 0 (pre-dose), 1, 2, 3, 4, 6, 8, 24 (0 hour [pre-dose] on Day 15) hours post-dose on Day 14 | AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption. Steady state concentration was achieved at Day 15. |
| Maximum Observed Plasma Concentration (Cmax) | 0 hour (pre-dose) on Day 1, 0 (pre-dose), 1, 2, 3, 4, 6, 8, 24 (0 hour [pre-dose] on Day 15) hours post-dose on Day 14 | — |
| Maximum Tolerated Dose (MTD) for Prolonged Use | Part 1 Day 1 up to Day 28 | MTD for prolonged use was the highest dose level at which not more than 1 of 6 participants experienced DLT after 21 days of treatment (Cycle 1) and was selected as recommended dose in Phase 2, due to substantial number of Grade 2 gastrointestinal toxicities observed in the MTD lead-in cohort (500 mg). |
| Number of Participants With Change From Baseline in Laboratory Test Results | Baseline up to end of treatment (Week 95) | Criteria for potentially clinically significant (PCS) laboratory values: albumin \<20, hemoglobin \<80 gram/liter(g/L); alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase \>5\*upper limit of normal(ULN) milliunit/milliliter(mU/mL); bilirubin total, creatinine\>3\*ULN micromole/L; calcium \<1.75 and \>3.1,potassium \<3 and \>6, sodium \<130, glucose \<2.2,phosphorous \<0.6 millimole/L; international normalized ratio \>2\*ULN, partial thromboplastin time, prothrombin time \>2\*ULN seconds; platelet count \<50\*10\^9/L. Participants meeting at least 1 PCS criteria are reported. |
| Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | Baseline up to end of treatment (Week 95) | Number of participants with PCS ECG findings is reported on-therapy (OT) and at final visit (FV). Criteria for PCS ECG findings: heart rate (HR) =\<45 beats/minute (bpm) and decrease (Dec) \>15/\>=120 bpm and decrease of \>15 bpm; PR interval (Int) \>=220 millisecond (msec), increase (Inc) \>=20 msec, QRS Int \>=120 msec, corrected QT (QTc) and QTc using fridericia formula(QTcF) Int \>500 msec, increase \>60 msec; no sinus rhythm; overall ECG abnormal. Participants with at least 1 measurement exceeding the criteria for PCS are reported. |
| Concomitant Medications Used for Management of Adverse Events (AEs) | Day 1 up to end of treatment (Week 95) | Number of participants taking any non-study medications which were administered from Day 1 up to end of treatment (Week 95) as a management of an AE was to be reported. |
| Change From Baseline in Karnofsky Performance Score | Baseline up to end of treatment (Week 95) | Karnofsky performance score is used to quantify participant's general well-being and activities of daily life and participants are classified based on their functional impairment. Karnofsky performance score is 11 level score which ranges between 0 (death) to 100 (complete healthy status). Higher score means higher ability to perform daily tasks. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Gene Expression at Baseline | Baseline | Gene expression profile was evaluated by measuring transcript levels of messenger RNA (mRNA) in peripheral blood samples. Expression profiling of mRNA: done to measure the expressed genome of mRNA transcripts or done in a gene-specific targeted manner. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Part 1 Participants received bosutinib capsule orally once daily continuously in 21-day cycles in dose escalation schemes of 50 mg, 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, 600 mg, MTD-lead in (500 mg) until disease progression, unacceptable toxicity, or consent withdrawal. | 51 |
| RP2D 400 mg Participants with colorectal cancer, pancreatic cancer, NSCLC received RP2D of bosutinib (400 mg) capsule orally once daily continuously in 21-day cycles until disease progression, unacceptable toxicity, or consent withdrawal. | 100 |
| Total | 151 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part 1: Dose Escalation | Adverse Event | 0 | 1 | 0 | 1 | 1 | 0 | 3 | 0 | 0 | 0 | 0 |
| Part 1: Dose Escalation | Death | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Part 1: Dose Escalation | Disease Progression | 3 | 2 | 5 | 6 | 4 | 6 | 7 | 4 | 0 | 0 | 0 |
| Part 1: Dose Escalation | Symptomatic Deterioration | 1 | 1 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Part 1: Dose Escalation | Withdrawal by Subject | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 1 | 0 | 0 | 0 |
| Part 2: Recommended Phase 2 Dose (RP2D) | Death | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 21 | 29 | 15 |
| Part 2: Recommended Phase 2 Dose (RP2D) | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 2 | 3 |
| Part 2: Recommended Phase 2 Dose (RP2D) | Other | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 6 | 4 | 3 |
| Part 2: Recommended Phase 2 Dose (RP2D) | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 5 | 3 | 2 |
Baseline characteristics
| Characteristic | Part 1 | RP2D 400 mg | Total |
|---|---|---|---|
| Age Continuous | 57.00 years STANDARD_DEVIATION 12.67 | 60.30 years STANDARD_DEVIATION 11.48 | 59.10 years STANDARD_DEVIATION 11.95 |
| Sex: Female, Male Female | 29 Participants | 54 Participants | 83 Participants |
| Sex: Female, Male Male | 22 Participants | 46 Participants | 68 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 4 / 4 | 4 / 4 | 6 / 6 | 7 / 7 | 7 / 7 | 7 / 7 | 10 / 10 | 6 / 6 | 99 / 100 |
| serious Total, serious adverse events | 4 / 4 | 3 / 4 | 2 / 6 | 3 / 7 | 5 / 7 | 2 / 7 | 7 / 10 | 3 / 6 | 47 / 100 |
Outcome results
Primary
Duration of Most Frequently Observed Adverse Events (AEs)
The most frequently observed treatment-emergent AEs were gastrointestinal disorders which included diarrhea, nausea and vomiting. Duration of AE per event is calculated as AE stop date minus AE start date plus 1.
Time frame: Baseline up to 30 days after last dose
Population: Safety population included all participants who had taken at least 1 dose of study medication.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Bosutinib 50 mg | Duration of Most Frequently Observed Adverse Events (AEs) | Diarrhea | 1.0 days |
| Bosutinib 50 mg | Duration of Most Frequently Observed Adverse Events (AEs) | Vomiting | 2.5 days |
| Bosutinib 50 mg | Duration of Most Frequently Observed Adverse Events (AEs) | Nausea | 2.0 days |
| Bosutinib 100 mg | Duration of Most Frequently Observed Adverse Events (AEs) | Vomiting | 1.0 days |
| Bosutinib 100 mg | Duration of Most Frequently Observed Adverse Events (AEs) | Nausea | 1.0 days |
| Bosutinib 100 mg | Duration of Most Frequently Observed Adverse Events (AEs) | Diarrhea | NA days |
| Bosutinib 200 mg | Duration of Most Frequently Observed Adverse Events (AEs) | Nausea | 1.0 days |
| Bosutinib 200 mg | Duration of Most Frequently Observed Adverse Events (AEs) | Diarrhea | 12.0 days |
| Bosutinib 200 mg | Duration of Most Frequently Observed Adverse Events (AEs) | Vomiting | NA days |
| Bosutinib 300 mg | Duration of Most Frequently Observed Adverse Events (AEs) | Nausea | 9.0 days |
| Bosutinib 300 mg | Duration of Most Frequently Observed Adverse Events (AEs) | Diarrhea | 2.0 days |
| Bosutinib 300 mg | Duration of Most Frequently Observed Adverse Events (AEs) | Vomiting | 1.0 days |
| Bosutinib 400 mg | Duration of Most Frequently Observed Adverse Events (AEs) | Diarrhea | 3.5 days |
| Bosutinib 400 mg | Duration of Most Frequently Observed Adverse Events (AEs) | Vomiting | 3.0 days |
| Bosutinib 400 mg | Duration of Most Frequently Observed Adverse Events (AEs) | Nausea | 4.0 days |
| Bosutinib 500 mg | Duration of Most Frequently Observed Adverse Events (AEs) | Nausea | 7.0 days |
| Bosutinib 500 mg | Duration of Most Frequently Observed Adverse Events (AEs) | Vomiting | 1.0 days |
| Bosutinib 500 mg | Duration of Most Frequently Observed Adverse Events (AEs) | Diarrhea | 7.0 days |
| Bosutinib 600 mg | Duration of Most Frequently Observed Adverse Events (AEs) | Nausea | 3.0 days |
| Bosutinib 600 mg | Duration of Most Frequently Observed Adverse Events (AEs) | Vomiting | 2.0 days |
| Bosutinib 600 mg | Duration of Most Frequently Observed Adverse Events (AEs) | Diarrhea | 1.0 days |
| MTD-lead in | Duration of Most Frequently Observed Adverse Events (AEs) | Vomiting | 2.5 days |
| MTD-lead in | Duration of Most Frequently Observed Adverse Events (AEs) | Diarrhea | 1.0 days |
| MTD-lead in | Duration of Most Frequently Observed Adverse Events (AEs) | Nausea | 7.0 days |
| RP2D 400 mg | Duration of Most Frequently Observed Adverse Events (AEs) | Nausea | 13.0 days |
| RP2D 400 mg | Duration of Most Frequently Observed Adverse Events (AEs) | Diarrhea | 3.0 days |
| RP2D 400 mg | Duration of Most Frequently Observed Adverse Events (AEs) | Vomiting | 2.0 days |
Primary
Maximum Tolerated Dose (MTD) in Part 1
MTD: highest dose level at which not more than 1 of 6 participants experienced DLT after 21 days of treatment (Cycle 1). DLT included any grade 3 or 4 clinically-evident non-hematologic toxicity, grade 4 neutropenia of \>= 7-day duration or with fever \>= 38.5 degrees Celsius (febrile neutropenia); grade 4 thrombocytopenia \>= 2-day duration or with bleeding requiring platelet transfusion, any clinically-significant grade \>= 2 toxicity that requires \>=14 days to resolve (to =\< grade 1) which occurred in first 21 days of study and considered at least possibly related to bosutinib.
Time frame: Part 1 Day 1 up to Day 28
Population: Safety population included all participants enrolled in a dose escalation cohort who had taken at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bosutinib 50 mg | Maximum Tolerated Dose (MTD) in Part 1 | 500 mg |
Primary
Number of Participants With Adverse Events (AEs) by Seriousness
Counts of participants who had treatment-emergent adverse events (TEAEs), defined as newly occurring or worsening after first dose. Participants with multiple occurrences of an AE within a category were counted once within the category.
Time frame: Baseline up to 30 days after last dose
Population: Safety population included all participants who had taken at least 1 dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bosutinib 50 mg | Number of Participants With Adverse Events (AEs) by Seriousness | AEs | 4 participants |
| Bosutinib 50 mg | Number of Participants With Adverse Events (AEs) by Seriousness | Serious adverse events (SAEs) | 4 participants |
| Bosutinib 100 mg | Number of Participants With Adverse Events (AEs) by Seriousness | AEs | 4 participants |
| Bosutinib 100 mg | Number of Participants With Adverse Events (AEs) by Seriousness | Serious adverse events (SAEs) | 3 participants |
| Bosutinib 200 mg | Number of Participants With Adverse Events (AEs) by Seriousness | AEs | 6 participants |
| Bosutinib 200 mg | Number of Participants With Adverse Events (AEs) by Seriousness | Serious adverse events (SAEs) | 2 participants |
| Bosutinib 300 mg | Number of Participants With Adverse Events (AEs) by Seriousness | AEs | 7 participants |
| Bosutinib 300 mg | Number of Participants With Adverse Events (AEs) by Seriousness | Serious adverse events (SAEs) | 3 participants |
| Bosutinib 400 mg | Number of Participants With Adverse Events (AEs) by Seriousness | AEs | 7 participants |
| Bosutinib 400 mg | Number of Participants With Adverse Events (AEs) by Seriousness | Serious adverse events (SAEs) | 5 participants |
| Bosutinib 500 mg | Number of Participants With Adverse Events (AEs) by Seriousness | Serious adverse events (SAEs) | 2 participants |
| Bosutinib 500 mg | Number of Participants With Adverse Events (AEs) by Seriousness | AEs | 7 participants |
| Bosutinib 600 mg | Number of Participants With Adverse Events (AEs) by Seriousness | Serious adverse events (SAEs) | 7 participants |
| Bosutinib 600 mg | Number of Participants With Adverse Events (AEs) by Seriousness | AEs | 10 participants |
| MTD-lead in | Number of Participants With Adverse Events (AEs) by Seriousness | AEs | 6 participants |
| MTD-lead in | Number of Participants With Adverse Events (AEs) by Seriousness | Serious adverse events (SAEs) | 3 participants |
| RP2D 400 mg | Number of Participants With Adverse Events (AEs) by Seriousness | AEs | 100 participants |
| RP2D 400 mg | Number of Participants With Adverse Events (AEs) by Seriousness | Serious adverse events (SAEs) | 47 participants |
Primary
Number of Participants With Best Overall Response (BOR) in Part 1
BOR:investigator assessment by modified Response Evaluation Criteria in Solid Tumors (RECIST), recorded from treatment start until disease progression/recurrence. Complete Response:disappearance of all lesions. Partial Response (PR):\>=30% decrease in sum of longest diameters (SLDs) of target lesions (TLs) taking as reference baseline SLD. Progressive disease (PD):\>=20% increase in SLD of TLs taking as reference smallest SLD since treatment start, or appearance of \>=1 new lesion. Stable disease: neither shrinkage for PR nor increase for PD taking as reference smallest SLD since treatment start.
Time frame: Part 1 Baseline, last week (Day 15 to 23) of cycles 2, 4, 6, 8 and thereafter every 3 cycles up to 30 days after last dose
Population: Efficacy evaluable population: participants who received at least 1 cycle (15 doses) of study medication, had no eligibility violations, did not use prohibited anti-cancer treatment, had baseline disease assessment, at least 1 disease assessment post-baseline/had experienced clinical progression/death before first post-baseline disease assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bosutinib 50 mg | Number of Participants With Best Overall Response (BOR) in Part 1 | Not done | 0 participants |
| Bosutinib 50 mg | Number of Participants With Best Overall Response (BOR) in Part 1 | Complete response | 0 participants |
| Bosutinib 50 mg | Number of Participants With Best Overall Response (BOR) in Part 1 | Partial response | 0 participants |
| Bosutinib 50 mg | Number of Participants With Best Overall Response (BOR) in Part 1 | Stable disease | 0 participants |
| Bosutinib 50 mg | Number of Participants With Best Overall Response (BOR) in Part 1 | Indeterminate | 0 participants |
| Bosutinib 50 mg | Number of Participants With Best Overall Response (BOR) in Part 1 | Progressive disease | 3 participants |
| Bosutinib 100 mg | Number of Participants With Best Overall Response (BOR) in Part 1 | Stable disease | 2 participants |
| Bosutinib 100 mg | Number of Participants With Best Overall Response (BOR) in Part 1 | Complete response | 0 participants |
| Bosutinib 100 mg | Number of Participants With Best Overall Response (BOR) in Part 1 | Progressive disease | 1 participants |
| Bosutinib 100 mg | Number of Participants With Best Overall Response (BOR) in Part 1 | Not done | 0 participants |
| Bosutinib 100 mg | Number of Participants With Best Overall Response (BOR) in Part 1 | Partial response | 0 participants |
| Bosutinib 100 mg | Number of Participants With Best Overall Response (BOR) in Part 1 | Indeterminate | 0 participants |
| Bosutinib 200 mg | Number of Participants With Best Overall Response (BOR) in Part 1 | Indeterminate | 0 participants |
| Bosutinib 200 mg | Number of Participants With Best Overall Response (BOR) in Part 1 | Stable disease | 2 participants |
| Bosutinib 200 mg | Number of Participants With Best Overall Response (BOR) in Part 1 | Partial response | 0 participants |
| Bosutinib 200 mg | Number of Participants With Best Overall Response (BOR) in Part 1 | Progressive disease | 4 participants |
| Bosutinib 200 mg | Number of Participants With Best Overall Response (BOR) in Part 1 | Not done | 0 participants |
| Bosutinib 200 mg | Number of Participants With Best Overall Response (BOR) in Part 1 | Complete response | 0 participants |
| Bosutinib 300 mg | Number of Participants With Best Overall Response (BOR) in Part 1 | Indeterminate | 0 participants |
| Bosutinib 300 mg | Number of Participants With Best Overall Response (BOR) in Part 1 | Complete response | 0 participants |
| Bosutinib 300 mg | Number of Participants With Best Overall Response (BOR) in Part 1 | Partial response | 0 participants |
| Bosutinib 300 mg | Number of Participants With Best Overall Response (BOR) in Part 1 | Stable disease | 5 participants |
| Bosutinib 300 mg | Number of Participants With Best Overall Response (BOR) in Part 1 | Progressive disease | 1 participants |
| Bosutinib 300 mg | Number of Participants With Best Overall Response (BOR) in Part 1 | Not done | 0 participants |
| Bosutinib 400 mg | Number of Participants With Best Overall Response (BOR) in Part 1 | Indeterminate | 1 participants |
| Bosutinib 400 mg | Number of Participants With Best Overall Response (BOR) in Part 1 | Partial response | 0 participants |
| Bosutinib 400 mg | Number of Participants With Best Overall Response (BOR) in Part 1 | Not done | 0 participants |
| Bosutinib 400 mg | Number of Participants With Best Overall Response (BOR) in Part 1 | Complete response | 0 participants |
| Bosutinib 400 mg | Number of Participants With Best Overall Response (BOR) in Part 1 | Progressive disease | 2 participants |
| Bosutinib 400 mg | Number of Participants With Best Overall Response (BOR) in Part 1 | Stable disease | 3 participants |
| Bosutinib 500 mg | Number of Participants With Best Overall Response (BOR) in Part 1 | Stable disease | 2 participants |
| Bosutinib 500 mg | Number of Participants With Best Overall Response (BOR) in Part 1 | Progressive disease | 3 participants |
| Bosutinib 500 mg | Number of Participants With Best Overall Response (BOR) in Part 1 | Partial response | 1 participants |
| Bosutinib 500 mg | Number of Participants With Best Overall Response (BOR) in Part 1 | Indeterminate | 0 participants |
| Bosutinib 500 mg | Number of Participants With Best Overall Response (BOR) in Part 1 | Complete response | 0 participants |
| Bosutinib 500 mg | Number of Participants With Best Overall Response (BOR) in Part 1 | Not done | 0 participants |
| Bosutinib 600 mg | Number of Participants With Best Overall Response (BOR) in Part 1 | Progressive disease | 0 participants |
| Bosutinib 600 mg | Number of Participants With Best Overall Response (BOR) in Part 1 | Indeterminate | 0 participants |
| Bosutinib 600 mg | Number of Participants With Best Overall Response (BOR) in Part 1 | Complete response | 0 participants |
| Bosutinib 600 mg | Number of Participants With Best Overall Response (BOR) in Part 1 | Stable disease | 4 participants |
| Bosutinib 600 mg | Number of Participants With Best Overall Response (BOR) in Part 1 | Not done | 0 participants |
| Bosutinib 600 mg | Number of Participants With Best Overall Response (BOR) in Part 1 | Partial response | 0 participants |
| MTD-lead in | Number of Participants With Best Overall Response (BOR) in Part 1 | Progressive disease | 1 participants |
| MTD-lead in | Number of Participants With Best Overall Response (BOR) in Part 1 | Stable disease | 2 participants |
| MTD-lead in | Number of Participants With Best Overall Response (BOR) in Part 1 | Not done | 0 participants |
| MTD-lead in | Number of Participants With Best Overall Response (BOR) in Part 1 | Indeterminate | 0 participants |
| MTD-lead in | Number of Participants With Best Overall Response (BOR) in Part 1 | Complete response | 0 participants |
| MTD-lead in | Number of Participants With Best Overall Response (BOR) in Part 1 | Partial response | 0 participants |
Primary
Number of Participants With Best Overall Response (BOR) in Part 2
BOR: investigator assessment by modified RECIST, recorded from treatment start until disease progression/recurrence. Complete Response: disappearance of all lesions. PR: \>=30% decrease in SLDs of TLs taking as reference baseline SLD. PD: \>=20% increase in SLD of TLs taking as reference smallest SLD since treatment start, or appearance of \>=1 new lesion. Stable disease: neither shrinkage for PR nor increase for PD taking as reference smallest SLD since treatment start.
Time frame: Part 2 Baseline, last week (Day 15 to 23) of cycles 2, 4, 6, 8 and thereafter every 3 cycles up to 30 days after last dose
Population: Efficacy evaluable population: participants who received at least 1 cycle (15 doses) of study medication, had no eligibility violations, did not use prohibited anti-cancer treatment, had baseline disease assessment, at least 1 disease assessment post-baseline/had experienced clinical progression/death before first post-baseline disease assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bosutinib 50 mg | Number of Participants With Best Overall Response (BOR) in Part 2 | Complete response | 0 participants |
| Bosutinib 50 mg | Number of Participants With Best Overall Response (BOR) in Part 2 | Partial response | 0 participants |
| Bosutinib 50 mg | Number of Participants With Best Overall Response (BOR) in Part 2 | Stable disease | 10 participants |
| Bosutinib 50 mg | Number of Participants With Best Overall Response (BOR) in Part 2 | Progressive disease | 24 participants |
| Bosutinib 50 mg | Number of Participants With Best Overall Response (BOR) in Part 2 | Indeterminate | 0 participants |
| Bosutinib 50 mg | Number of Participants With Best Overall Response (BOR) in Part 2 | Not done | 0 participants |
| Bosutinib 100 mg | Number of Participants With Best Overall Response (BOR) in Part 2 | Not done | 1 participants |
| Bosutinib 100 mg | Number of Participants With Best Overall Response (BOR) in Part 2 | Complete response | 0 participants |
| Bosutinib 100 mg | Number of Participants With Best Overall Response (BOR) in Part 2 | Progressive disease | 18 participants |
| Bosutinib 100 mg | Number of Participants With Best Overall Response (BOR) in Part 2 | Indeterminate | 0 participants |
| Bosutinib 100 mg | Number of Participants With Best Overall Response (BOR) in Part 2 | Partial response | 0 participants |
| Bosutinib 100 mg | Number of Participants With Best Overall Response (BOR) in Part 2 | Stable disease | 3 participants |
| Bosutinib 200 mg | Number of Participants With Best Overall Response (BOR) in Part 2 | Partial response | 0 participants |
| Bosutinib 200 mg | Number of Participants With Best Overall Response (BOR) in Part 2 | Stable disease | 9 participants |
| Bosutinib 200 mg | Number of Participants With Best Overall Response (BOR) in Part 2 | Not done | 1 participants |
| Bosutinib 200 mg | Number of Participants With Best Overall Response (BOR) in Part 2 | Progressive disease | 9 participants |
| Bosutinib 200 mg | Number of Participants With Best Overall Response (BOR) in Part 2 | Complete response | 0 participants |
| Bosutinib 200 mg | Number of Participants With Best Overall Response (BOR) in Part 2 | Indeterminate | 0 participants |
Primary
Number of Participants With Dose-limiting Toxicities (DLT) in Part 1
DLT included any grade 3 or 4 clinically-evident non-hematologic toxicity, grade 4 neutropenia of greater than or equal to (\>=) 7-day duration or with fever \>= 38.5 degrees Celsius (febrile neutropenia); grade 4 thrombocytopenia \>= 2-day duration or with bleeding requiring platelet transfusion, any clinically-significant grade \>= 2 toxicity that requires \>=14 days to resolve (to less than or equal to \[=\<\] grade 1) which occurred in first 21 days of study and considered at least possibly related to bosutinib.
Time frame: Part 1 Baseline up to Day 28
Population: Safety population included all participants enrolled in a dose escalation cohort who had taken at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bosutinib 50 mg | Number of Participants With Dose-limiting Toxicities (DLT) in Part 1 | 0 participants |
| Bosutinib 100 mg | Number of Participants With Dose-limiting Toxicities (DLT) in Part 1 | 0 participants |
| Bosutinib 200 mg | Number of Participants With Dose-limiting Toxicities (DLT) in Part 1 | 1 participants |
| Bosutinib 300 mg | Number of Participants With Dose-limiting Toxicities (DLT) in Part 1 | 1 participants |
| Bosutinib 400 mg | Number of Participants With Dose-limiting Toxicities (DLT) in Part 1 | 0 participants |
| Bosutinib 500 mg | Number of Participants With Dose-limiting Toxicities (DLT) in Part 1 | 1 participants |
| Bosutinib 600 mg | Number of Participants With Dose-limiting Toxicities (DLT) in Part 1 | 3 participants |
| MTD-lead in | Number of Participants With Dose-limiting Toxicities (DLT) in Part 1 | 0 participants |
Secondary
Area Under the Concentration-Time Curve (AUC)
AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption. Steady state concentration was achieved at Day 15.
Time frame: 0 hour (pre-dose) on Day 1, 0 (pre-dose), 1, 2, 3, 4, 6, 8, 24 (0 hour [pre-dose] on Day 15) hours post-dose on Day 14
Population: Analysis population included all participants who had taken at least 1 dose of study medication. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure and 'n' signifies those participants evaluable for specific time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Bosutinib 50 mg | Area Under the Concentration-Time Curve (AUC) | Day 1 (n = 3, 4, 6, 7, 47, 13, 10) | 129.0 ng*hour/mL | Standard Deviation 131 |
| Bosutinib 50 mg | Area Under the Concentration-Time Curve (AUC) | Day 15 (n = 3, 4, 5, 4, 58, 9, 2) | 114.0 ng*hour/mL | Standard Deviation 33.3 |
| Bosutinib 100 mg | Area Under the Concentration-Time Curve (AUC) | Day 1 (n = 3, 4, 6, 7, 47, 13, 10) | 284.0 ng*hour/mL | Standard Deviation 72.8 |
| Bosutinib 100 mg | Area Under the Concentration-Time Curve (AUC) | Day 15 (n = 3, 4, 5, 4, 58, 9, 2) | 329.0 ng*hour/mL | Standard Deviation 58.1 |
| Bosutinib 200 mg | Area Under the Concentration-Time Curve (AUC) | Day 1 (n = 3, 4, 6, 7, 47, 13, 10) | 920.0 ng*hour/mL | Standard Deviation 338 |
| Bosutinib 200 mg | Area Under the Concentration-Time Curve (AUC) | Day 15 (n = 3, 4, 5, 4, 58, 9, 2) | 1670.0 ng*hour/mL | Standard Deviation 1130 |
| Bosutinib 300 mg | Area Under the Concentration-Time Curve (AUC) | Day 1 (n = 3, 4, 6, 7, 47, 13, 10) | 1200.0 ng*hour/mL | Standard Deviation 736 |
| Bosutinib 300 mg | Area Under the Concentration-Time Curve (AUC) | Day 15 (n = 3, 4, 5, 4, 58, 9, 2) | 1170.0 ng*hour/mL | Standard Deviation 699 |
| Bosutinib 400 mg | Area Under the Concentration-Time Curve (AUC) | Day 1 (n = 3, 4, 6, 7, 47, 13, 10) | 2340.0 ng*hour/mL | Standard Deviation 1230 |
| Bosutinib 400 mg | Area Under the Concentration-Time Curve (AUC) | Day 15 (n = 3, 4, 5, 4, 58, 9, 2) | 2900.0 ng*hour/mL | Standard Deviation 1700 |
| Bosutinib 500 mg | Area Under the Concentration-Time Curve (AUC) | Day 1 (n = 3, 4, 6, 7, 47, 13, 10) | 2950.0 ng*hour/mL | Standard Deviation 1470 |
| Bosutinib 500 mg | Area Under the Concentration-Time Curve (AUC) | Day 15 (n = 3, 4, 5, 4, 58, 9, 2) | 3580.0 ng*hour/mL | Standard Deviation 1820 |
| Bosutinib 600 mg | Area Under the Concentration-Time Curve (AUC) | Day 1 (n = 3, 4, 6, 7, 47, 13, 10) | 4300.0 ng*hour/mL | Standard Deviation 3310 |
| Bosutinib 600 mg | Area Under the Concentration-Time Curve (AUC) | Day 15 (n = 3, 4, 5, 4, 58, 9, 2) | 4220.0 ng*hour/mL | — |
Secondary
Change From Baseline in Karnofsky Performance Score
Karnofsky performance score is used to quantify participant's general well-being and activities of daily life and participants are classified based on their functional impairment. Karnofsky performance score is 11 level score which ranges between 0 (death) to 100 (complete healthy status). Higher score means higher ability to perform daily tasks.
Time frame: Baseline up to end of treatment (Week 95)
Population: Data for this pre-specified outcome was collected but not statistically summarized for analysis as there were no clinically significant changes observed.
Secondary
Concomitant Medications Used for Management of Adverse Events (AEs)
Number of participants taking any non-study medications which were administered from Day 1 up to end of treatment (Week 95) as a management of an AE was to be reported.
Time frame: Day 1 up to end of treatment (Week 95)
Population: Data for this pre-specified outcome measure was not statistically summarized for analysis, but collected and reported in individual participant listings as planned.
Secondary
Maximum Observed Plasma Concentration (Cmax)
Time frame: 0 hour (pre-dose) on Day 1, 0 (pre-dose), 1, 2, 3, 4, 6, 8, 24 (0 hour [pre-dose] on Day 15) hours post-dose on Day 14
Population: Analysis population included all participants who had taken at least 1 dose of study medication. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure and 'n' signifies those participants evaluable for specific time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Bosutinib 50 mg | Maximum Observed Plasma Concentration (Cmax) | Day 1 (n = 4, 4, 6, 7, 54, 13, 10) | 4.89 nanogram/milliliter (ng/mL) | Standard Deviation 3.69 |
| Bosutinib 50 mg | Maximum Observed Plasma Concentration (Cmax) | Day 15 (n = 3, 4, 5, 5, 69, 10, 2) | 6.92 nanogram/milliliter (ng/mL) | Standard Deviation 3.07 |
| Bosutinib 100 mg | Maximum Observed Plasma Concentration (Cmax) | Day 1 (n = 4, 4, 6, 7, 54, 13, 10) | 17.0 nanogram/milliliter (ng/mL) | Standard Deviation 9.75 |
| Bosutinib 100 mg | Maximum Observed Plasma Concentration (Cmax) | Day 15 (n = 3, 4, 5, 5, 69, 10, 2) | 19.6 nanogram/milliliter (ng/mL) | Standard Deviation 3.31 |
| Bosutinib 200 mg | Maximum Observed Plasma Concentration (Cmax) | Day 1 (n = 4, 4, 6, 7, 54, 13, 10) | 43.1 nanogram/milliliter (ng/mL) | Standard Deviation 26.9 |
| Bosutinib 200 mg | Maximum Observed Plasma Concentration (Cmax) | Day 15 (n = 3, 4, 5, 5, 69, 10, 2) | 95.4 nanogram/milliliter (ng/mL) | Standard Deviation 60 |
| Bosutinib 300 mg | Maximum Observed Plasma Concentration (Cmax) | Day 1 (n = 4, 4, 6, 7, 54, 13, 10) | 63.7 nanogram/milliliter (ng/mL) | Standard Deviation 34.7 |
| Bosutinib 300 mg | Maximum Observed Plasma Concentration (Cmax) | Day 15 (n = 3, 4, 5, 5, 69, 10, 2) | 76.6 nanogram/milliliter (ng/mL) | Standard Deviation 37 |
| Bosutinib 400 mg | Maximum Observed Plasma Concentration (Cmax) | Day 1 (n = 4, 4, 6, 7, 54, 13, 10) | 117.0 nanogram/milliliter (ng/mL) | Standard Deviation 69 |
| Bosutinib 400 mg | Maximum Observed Plasma Concentration (Cmax) | Day 15 (n = 3, 4, 5, 5, 69, 10, 2) | 190.0 nanogram/milliliter (ng/mL) | Standard Deviation 116 |
| Bosutinib 500 mg | Maximum Observed Plasma Concentration (Cmax) | Day 1 (n = 4, 4, 6, 7, 54, 13, 10) | 125.0 nanogram/milliliter (ng/mL) | Standard Deviation 63.2 |
| Bosutinib 500 mg | Maximum Observed Plasma Concentration (Cmax) | Day 15 (n = 3, 4, 5, 5, 69, 10, 2) | 273.0 nanogram/milliliter (ng/mL) | Standard Deviation 197 |
| Bosutinib 600 mg | Maximum Observed Plasma Concentration (Cmax) | Day 1 (n = 4, 4, 6, 7, 54, 13, 10) | 206.0 nanogram/milliliter (ng/mL) | Standard Deviation 190 |
| Bosutinib 600 mg | Maximum Observed Plasma Concentration (Cmax) | Day 15 (n = 3, 4, 5, 5, 69, 10, 2) | 304.0 nanogram/milliliter (ng/mL) | — |
Secondary
Maximum Tolerated Dose (MTD) for Prolonged Use
MTD for prolonged use was the highest dose level at which not more than 1 of 6 participants experienced DLT after 21 days of treatment (Cycle 1) and was selected as recommended dose in Phase 2, due to substantial number of Grade 2 gastrointestinal toxicities observed in the MTD lead-in cohort (500 mg).
Time frame: Part 1 Day 1 up to Day 28
Population: Safety population included all participants enrolled in a dose escalation cohort who had taken at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bosutinib 50 mg | Maximum Tolerated Dose (MTD) for Prolonged Use | 400 mg |
Secondary
Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray
Number of participants with PCS ECG findings is reported on-therapy (OT) and at final visit (FV). Criteria for PCS ECG findings: heart rate (HR) =\<45 beats/minute (bpm) and decrease (Dec) \>15/\>=120 bpm and decrease of \>15 bpm; PR interval (Int) \>=220 millisecond (msec), increase (Inc) \>=20 msec, QRS Int \>=120 msec, corrected QT (QTc) and QTc using fridericia formula(QTcF) Int \>500 msec, increase \>60 msec; no sinus rhythm; overall ECG abnormal. Participants with at least 1 measurement exceeding the criteria for PCS are reported.
Time frame: Baseline up to end of treatment (Week 95)
Population: Safety population included all participants who had taken at least 1 dose of study medication. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable (at least 1 on-therapy assessment) for this measure and 'n' represents participants evaluable under each category for each group respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bosutinib 50 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: QTcF Int (>500 msec) (n=0,0,0,0,0,0,1,3,89) | 0 participants |
| Bosutinib 50 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | FV: Overall ECG abnormal (n=1,2,3,4,3,4,3,1,42) | 1 participants |
| Bosutinib 50 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT:PR Int(>=220/Inc>20msec)(n=4,4,6,7,7,7,10,6,93) | 0 participants |
| Bosutinib 50 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | FV:PR Int(>=220/Inc >20msec)(n=1,2,3,4,3,4,3,1,42) | 0 participants |
| Bosutinib 50 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: QTc Int (Inc >60 msec) (n=4,4,6,7,7,7,10,6,93) | 0 participants |
| Bosutinib 50 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | FV: No sinus rhythm (n=1,2,2,4,3,4,3,1,42) | 0 participants |
| Bosutinib 50 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: QRS Int (>=120 msec) (n=4,4,6,7,7,7,10,6,93) | 0 participants |
| Bosutinib 50 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: QTcF Int (Inc >60 msec) (n=0,0,0,0,0,0,1,3,89) | 0 participants |
| Bosutinib 50 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: Overall ECG abnormal (n=4,4,6,7,7,7,10,6,93) | 3 participants |
| Bosutinib 50 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | Chest X-ray (n=0,0,0,0,0,0,0,0,0) | NA participants |
| Bosutinib 50 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: HR (>=120/Inc >15bpm) (n=4,4,6,7,7,7,10,6,93) | 1 participants |
| Bosutinib 50 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | FV: HR (>=120/Inc >15bpm) (n=1,2,2,4,3,4,3,1,42) | 0 participants |
| Bosutinib 50 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | FV: QRS Int (>=120 msec) (n=1,2,2,4,3,4,3,1,42) | 0 participants |
| Bosutinib 50 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: QTc Int (>500 msec) (n=4,4,6,7,7,7,10,6,93) | 0 participants |
| Bosutinib 50 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: No sinus rhythm (n=4,4,6,7,7,7,10,6,93) | 0 participants |
| Bosutinib 50 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | FV: QTc Int (>500 msec) (n=1,2,3,4,3,4,3,1,42) | 0 participants |
| Bosutinib 50 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: HR (<=45/Dec >15bpm) (n=4,4,6,7,7,7,10,6,93) | 0 participants |
| Bosutinib 100 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | Chest X-ray (n=0,0,0,0,0,0,0,0,0) | NA participants |
| Bosutinib 100 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: Overall ECG abnormal (n=4,4,6,7,7,7,10,6,93) | 4 participants |
| Bosutinib 100 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: No sinus rhythm (n=4,4,6,7,7,7,10,6,93) | 0 participants |
| Bosutinib 100 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: HR (>=120/Inc >15bpm) (n=4,4,6,7,7,7,10,6,93) | 0 participants |
| Bosutinib 100 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: HR (<=45/Dec >15bpm) (n=4,4,6,7,7,7,10,6,93) | 0 participants |
| Bosutinib 100 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | FV: Overall ECG abnormal (n=1,2,3,4,3,4,3,1,42) | 1 participants |
| Bosutinib 100 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT:PR Int(>=220/Inc>20msec)(n=4,4,6,7,7,7,10,6,93) | 0 participants |
| Bosutinib 100 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | FV: No sinus rhythm (n=1,2,2,4,3,4,3,1,42) | 0 participants |
| Bosutinib 100 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: QRS Int (>=120 msec) (n=4,4,6,7,7,7,10,6,93) | 0 participants |
| Bosutinib 100 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | FV: QTc Int (>500 msec) (n=1,2,3,4,3,4,3,1,42) | 0 participants |
| Bosutinib 100 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: QTc Int (Inc >60 msec) (n=4,4,6,7,7,7,10,6,93) | 0 participants |
| Bosutinib 100 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | FV: QRS Int (>=120 msec) (n=1,2,2,4,3,4,3,1,42) | 0 participants |
| Bosutinib 100 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: QTc Int (>500 msec) (n=4,4,6,7,7,7,10,6,93) | 0 participants |
| Bosutinib 100 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | FV:PR Int(>=220/Inc >20msec)(n=1,2,3,4,3,4,3,1,42) | 0 participants |
| Bosutinib 100 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: QTcF Int (Inc >60 msec) (n=0,0,0,0,0,0,1,3,89) | 0 participants |
| Bosutinib 100 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | FV: HR (>=120/Inc >15bpm) (n=1,2,2,4,3,4,3,1,42) | 0 participants |
| Bosutinib 100 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: QTcF Int (>500 msec) (n=0,0,0,0,0,0,1,3,89) | 0 participants |
| Bosutinib 200 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | FV: QRS Int (>=120 msec) (n=1,2,2,4,3,4,3,1,42) | 0 participants |
| Bosutinib 200 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | FV:PR Int(>=220/Inc >20msec)(n=1,2,3,4,3,4,3,1,42) | 1 participants |
| Bosutinib 200 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT:PR Int(>=220/Inc>20msec)(n=4,4,6,7,7,7,10,6,93) | 0 participants |
| Bosutinib 200 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | FV: Overall ECG abnormal (n=1,2,3,4,3,4,3,1,42) | 1 participants |
| Bosutinib 200 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: QTcF Int (>500 msec) (n=0,0,0,0,0,0,1,3,89) | 0 participants |
| Bosutinib 200 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: QTcF Int (Inc >60 msec) (n=0,0,0,0,0,0,1,3,89) | 0 participants |
| Bosutinib 200 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: Overall ECG abnormal (n=4,4,6,7,7,7,10,6,93) | 5 participants |
| Bosutinib 200 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: QTc Int (>500 msec) (n=4,4,6,7,7,7,10,6,93) | 1 participants |
| Bosutinib 200 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | FV: No sinus rhythm (n=1,2,2,4,3,4,3,1,42) | 0 participants |
| Bosutinib 200 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | Chest X-ray (n=0,0,0,0,0,0,0,0,0) | NA participants |
| Bosutinib 200 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: HR (<=45/Dec >15bpm) (n=4,4,6,7,7,7,10,6,93) | 0 participants |
| Bosutinib 200 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: No sinus rhythm (n=4,4,6,7,7,7,10,6,93) | 0 participants |
| Bosutinib 200 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: QRS Int (>=120 msec) (n=4,4,6,7,7,7,10,6,93) | 1 participants |
| Bosutinib 200 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | FV: HR (>=120/Inc >15bpm) (n=1,2,2,4,3,4,3,1,42) | 0 participants |
| Bosutinib 200 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: QTc Int (Inc >60 msec) (n=4,4,6,7,7,7,10,6,93) | 1 participants |
| Bosutinib 200 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: HR (>=120/Inc >15bpm) (n=4,4,6,7,7,7,10,6,93) | 1 participants |
| Bosutinib 200 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | FV: QTc Int (>500 msec) (n=1,2,3,4,3,4,3,1,42) | 0 participants |
| Bosutinib 300 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | FV: QTc Int (>500 msec) (n=1,2,3,4,3,4,3,1,42) | 0 participants |
| Bosutinib 300 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | FV: HR (>=120/Inc >15bpm) (n=1,2,2,4,3,4,3,1,42) | 0 participants |
| Bosutinib 300 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: QTc Int (Inc >60 msec) (n=4,4,6,7,7,7,10,6,93) | 0 participants |
| Bosutinib 300 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | FV: Overall ECG abnormal (n=1,2,3,4,3,4,3,1,42) | 0 participants |
| Bosutinib 300 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | FV: QRS Int (>=120 msec) (n=1,2,2,4,3,4,3,1,42) | 0 participants |
| Bosutinib 300 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: QTcF Int (>500 msec) (n=0,0,0,0,0,0,1,3,89) | 0 participants |
| Bosutinib 300 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: HR (>=120/Inc >15bpm) (n=4,4,6,7,7,7,10,6,93) | 0 participants |
| Bosutinib 300 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: QTc Int (>500 msec) (n=4,4,6,7,7,7,10,6,93) | 0 participants |
| Bosutinib 300 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | Chest X-ray (n=0,0,0,0,0,0,0,0,0) | NA participants |
| Bosutinib 300 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | FV:PR Int(>=220/Inc >20msec)(n=1,2,3,4,3,4,3,1,42) | 0 participants |
| Bosutinib 300 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: Overall ECG abnormal (n=4,4,6,7,7,7,10,6,93) | 7 participants |
| Bosutinib 300 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: No sinus rhythm (n=4,4,6,7,7,7,10,6,93) | 0 participants |
| Bosutinib 300 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: QTcF Int (Inc >60 msec) (n=0,0,0,0,0,0,1,3,89) | 0 participants |
| Bosutinib 300 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | FV: No sinus rhythm (n=1,2,2,4,3,4,3,1,42) | 0 participants |
| Bosutinib 300 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: QRS Int (>=120 msec) (n=4,4,6,7,7,7,10,6,93) | 1 participants |
| Bosutinib 300 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: HR (<=45/Dec >15bpm) (n=4,4,6,7,7,7,10,6,93) | 0 participants |
| Bosutinib 300 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT:PR Int(>=220/Inc>20msec)(n=4,4,6,7,7,7,10,6,93) | 0 participants |
| Bosutinib 400 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: No sinus rhythm (n=4,4,6,7,7,7,10,6,93) | 0 participants |
| Bosutinib 400 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: HR (<=45/Dec >15bpm) (n=4,4,6,7,7,7,10,6,93) | 0 participants |
| Bosutinib 400 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: HR (>=120/Inc >15bpm) (n=4,4,6,7,7,7,10,6,93) | 0 participants |
| Bosutinib 400 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT:PR Int(>=220/Inc>20msec)(n=4,4,6,7,7,7,10,6,93) | 0 participants |
| Bosutinib 400 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: QRS Int (>=120 msec) (n=4,4,6,7,7,7,10,6,93) | 1 participants |
| Bosutinib 400 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: QTc Int (Inc >60 msec) (n=4,4,6,7,7,7,10,6,93) | 0 participants |
| Bosutinib 400 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: QTc Int (>500 msec) (n=4,4,6,7,7,7,10,6,93) | 0 participants |
| Bosutinib 400 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: QTcF Int (Inc >60 msec) (n=0,0,0,0,0,0,1,3,89) | 0 participants |
| Bosutinib 400 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: QTcF Int (>500 msec) (n=0,0,0,0,0,0,1,3,89) | 0 participants |
| Bosutinib 400 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: Overall ECG abnormal (n=4,4,6,7,7,7,10,6,93) | 6 participants |
| Bosutinib 400 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | FV: HR (>=120/Inc >15bpm) (n=1,2,2,4,3,4,3,1,42) | 0 participants |
| Bosutinib 400 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | FV:PR Int(>=220/Inc >20msec)(n=1,2,3,4,3,4,3,1,42) | 0 participants |
| Bosutinib 400 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | FV: QRS Int (>=120 msec) (n=1,2,2,4,3,4,3,1,42) | 0 participants |
| Bosutinib 400 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | FV: QTc Int (>500 msec) (n=1,2,3,4,3,4,3,1,42) | 0 participants |
| Bosutinib 400 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | FV: No sinus rhythm (n=1,2,2,4,3,4,3,1,42) | 0 participants |
| Bosutinib 400 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | FV: Overall ECG abnormal (n=1,2,3,4,3,4,3,1,42) | 2 participants |
| Bosutinib 400 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | Chest X-ray (n=0,0,0,0,0,0,0,0,0) | NA participants |
| Bosutinib 500 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | FV: QTc Int (>500 msec) (n=1,2,3,4,3,4,3,1,42) | 0 participants |
| Bosutinib 500 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: HR (<=45/Dec >15bpm) (n=4,4,6,7,7,7,10,6,93) | 0 participants |
| Bosutinib 500 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | FV:PR Int(>=220/Inc >20msec)(n=1,2,3,4,3,4,3,1,42) | 0 participants |
| Bosutinib 500 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT:PR Int(>=220/Inc>20msec)(n=4,4,6,7,7,7,10,6,93) | 0 participants |
| Bosutinib 500 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: QTcF Int (>500 msec) (n=0,0,0,0,0,0,1,3,89) | 0 participants |
| Bosutinib 500 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | FV: Overall ECG abnormal (n=1,2,3,4,3,4,3,1,42) | 3 participants |
| Bosutinib 500 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: QTc Int (>500 msec) (n=4,4,6,7,7,7,10,6,93) | 1 participants |
| Bosutinib 500 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: HR (>=120/Inc >15bpm) (n=4,4,6,7,7,7,10,6,93) | 0 participants |
| Bosutinib 500 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | Chest X-ray (n=0,0,0,0,0,0,0,0,0) | NA participants |
| Bosutinib 500 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: Overall ECG abnormal (n=4,4,6,7,7,7,10,6,93) | 6 participants |
| Bosutinib 500 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: No sinus rhythm (n=4,4,6,7,7,7,10,6,93) | 0 participants |
| Bosutinib 500 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | FV: QRS Int (>=120 msec) (n=1,2,2,4,3,4,3,1,42) | 0 participants |
| Bosutinib 500 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: QTcF Int (Inc >60 msec) (n=0,0,0,0,0,0,1,3,89) | 0 participants |
| Bosutinib 500 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: QRS Int (>=120 msec) (n=4,4,6,7,7,7,10,6,93) | 0 participants |
| Bosutinib 500 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | FV: HR (>=120/Inc >15bpm) (n=1,2,2,4,3,4,3,1,42) | 0 participants |
| Bosutinib 500 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: QTc Int (Inc >60 msec) (n=4,4,6,7,7,7,10,6,93) | 0 participants |
| Bosutinib 500 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | FV: No sinus rhythm (n=1,2,2,4,3,4,3,1,42) | 0 participants |
| Bosutinib 600 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: QTc Int (>500 msec) (n=4,4,6,7,7,7,10,6,93) | 0 participants |
| Bosutinib 600 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: QRS Int (>=120 msec) (n=4,4,6,7,7,7,10,6,93) | 1 participants |
| Bosutinib 600 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | FV: QTc Int (>500 msec) (n=1,2,3,4,3,4,3,1,42) | 0 participants |
| Bosutinib 600 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: HR (<=45/Dec >15bpm) (n=4,4,6,7,7,7,10,6,93) | 0 participants |
| Bosutinib 600 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | Chest X-ray (n=0,0,0,0,0,0,0,0,0) | NA participants |
| Bosutinib 600 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT:PR Int(>=220/Inc>20msec)(n=4,4,6,7,7,7,10,6,93) | 0 participants |
| Bosutinib 600 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | FV: HR (>=120/Inc >15bpm) (n=1,2,2,4,3,4,3,1,42) | 0 participants |
| Bosutinib 600 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | FV: Overall ECG abnormal (n=1,2,3,4,3,4,3,1,42) | 3 participants |
| Bosutinib 600 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: QTcF Int (>500 msec) (n=0,0,0,0,0,0,1,3,89) | 0 participants |
| Bosutinib 600 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: QTcF Int (Inc >60 msec) (n=0,0,0,0,0,0,1,3,89) | 0 participants |
| Bosutinib 600 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | FV:PR Int(>=220/Inc >20msec)(n=1,2,3,4,3,4,3,1,42) | 0 participants |
| Bosutinib 600 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: No sinus rhythm (n=4,4,6,7,7,7,10,6,93) | 0 participants |
| Bosutinib 600 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: QTc Int (Inc >60 msec) (n=4,4,6,7,7,7,10,6,93) | 0 participants |
| Bosutinib 600 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: HR (>=120/Inc >15bpm) (n=4,4,6,7,7,7,10,6,93) | 0 participants |
| Bosutinib 600 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | FV: QRS Int (>=120 msec) (n=1,2,2,4,3,4,3,1,42) | 1 participants |
| Bosutinib 600 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: Overall ECG abnormal (n=4,4,6,7,7,7,10,6,93) | 8 participants |
| Bosutinib 600 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | FV: No sinus rhythm (n=1,2,2,4,3,4,3,1,42) | 0 participants |
| MTD-lead in | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: HR (>=120/Inc >15bpm) (n=4,4,6,7,7,7,10,6,93) | 0 participants |
| MTD-lead in | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: Overall ECG abnormal (n=4,4,6,7,7,7,10,6,93) | 6 participants |
| MTD-lead in | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: QTcF Int (Inc >60 msec) (n=0,0,0,0,0,0,1,3,89) | 0 participants |
| MTD-lead in | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | FV: HR (>=120/Inc >15bpm) (n=1,2,2,4,3,4,3,1,42) | 0 participants |
| MTD-lead in | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: QTc Int (>500 msec) (n=4,4,6,7,7,7,10,6,93) | 0 participants |
| MTD-lead in | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | FV:PR Int(>=220/Inc >20msec)(n=1,2,3,4,3,4,3,1,42) | 0 participants |
| MTD-lead in | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: QTc Int (Inc >60 msec) (n=4,4,6,7,7,7,10,6,93) | 0 participants |
| MTD-lead in | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | FV: QRS Int (>=120 msec) (n=1,2,2,4,3,4,3,1,42) | 0 participants |
| MTD-lead in | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: QRS Int (>=120 msec) (n=4,4,6,7,7,7,10,6,93) | 0 participants |
| MTD-lead in | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | FV: QTc Int (>500 msec) (n=1,2,3,4,3,4,3,1,42) | 0 participants |
| MTD-lead in | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT:PR Int(>=220/Inc>20msec)(n=4,4,6,7,7,7,10,6,93) | 2 participants |
| MTD-lead in | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | FV: No sinus rhythm (n=1,2,2,4,3,4,3,1,42) | 0 participants |
| MTD-lead in | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: HR (<=45/Dec >15bpm) (n=4,4,6,7,7,7,10,6,93) | 0 participants |
| MTD-lead in | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | Chest X-ray (n=0,0,0,0,0,0,0,0,0) | NA participants |
| MTD-lead in | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | FV: Overall ECG abnormal (n=1,2,3,4,3,4,3,1,42) | 1 participants |
| MTD-lead in | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: No sinus rhythm (n=4,4,6,7,7,7,10,6,93) | 0 participants |
| MTD-lead in | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: QTcF Int (>500 msec) (n=0,0,0,0,0,0,1,3,89) | 0 participants |
| RP2D 400 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: No sinus rhythm (n=4,4,6,7,7,7,10,6,93) | 29 participants |
| RP2D 400 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | Chest X-ray (n=0,0,0,0,0,0,0,0,0) | NA participants |
| RP2D 400 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: QTc Int (Inc >60 msec) (n=4,4,6,7,7,7,10,6,93) | 3 participants |
| RP2D 400 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT:PR Int(>=220/Inc>20msec)(n=4,4,6,7,7,7,10,6,93) | 3 participants |
| RP2D 400 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | FV:PR Int(>=220/Inc >20msec)(n=1,2,3,4,3,4,3,1,42) | 0 participants |
| RP2D 400 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: QTc Int (>500 msec) (n=4,4,6,7,7,7,10,6,93) | 3 participants |
| RP2D 400 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: QTcF Int (>500 msec) (n=0,0,0,0,0,0,1,3,89) | 1 participants |
| RP2D 400 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | FV: Overall ECG abnormal (n=1,2,3,4,3,4,3,1,42) | 18 participants |
| RP2D 400 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: HR (<=45/Dec >15bpm) (n=4,4,6,7,7,7,10,6,93) | 1 participants |
| RP2D 400 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | FV: HR (>=120/Inc >15bpm) (n=1,2,2,4,3,4,3,1,42) | 1 participants |
| RP2D 400 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: QTcF Int (Inc >60 msec) (n=0,0,0,0,0,0,1,3,89) | 3 participants |
| RP2D 400 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | FV: QTc Int (>500 msec) (n=1,2,3,4,3,4,3,1,42) | 1 participants |
| RP2D 400 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: QRS Int (>=120 msec) (n=4,4,6,7,7,7,10,6,93) | 8 participants |
| RP2D 400 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | FV: QRS Int (>=120 msec) (n=1,2,2,4,3,4,3,1,42) | 4 participants |
| RP2D 400 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: Overall ECG abnormal (n=4,4,6,7,7,7,10,6,93) | 63 participants |
| RP2D 400 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | FV: No sinus rhythm (n=1,2,2,4,3,4,3,1,42) | 2 participants |
| RP2D 400 mg | Number of Participants With Change From Baseline in Electrocardiogram (ECG) and Chest X-ray | OT: HR (>=120/Inc >15bpm) (n=4,4,6,7,7,7,10,6,93) | 3 participants |
Secondary
Number of Participants With Change From Baseline in Laboratory Test Results
Criteria for potentially clinically significant (PCS) laboratory values: albumin \<20, hemoglobin \<80 gram/liter(g/L); alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase \>5\*upper limit of normal(ULN) milliunit/milliliter(mU/mL); bilirubin total, creatinine\>3\*ULN micromole/L; calcium \<1.75 and \>3.1,potassium \<3 and \>6, sodium \<130, glucose \<2.2,phosphorous \<0.6 millimole/L; international normalized ratio \>2\*ULN, partial thromboplastin time, prothrombin time \>2\*ULN seconds; platelet count \<50\*10\^9/L. Participants meeting at least 1 PCS criteria are reported.
Time frame: Baseline up to end of treatment (Week 95)
Population: Safety population included all participants who had taken at least 1 dose of study medication. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable (at least 1 on-therapy laboratory assessment) for this measure for each group respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bosutinib 50 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Platelets (<50*10^9/L) | 0 participants |
| Bosutinib 50 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Hemoglobin (<80 g/L) | 0 participants |
| Bosutinib 50 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Bilirubin total (>3*ULN) | 0 participants |
| Bosutinib 50 mg | Number of Participants With Change From Baseline in Laboratory Test Results | International normalized ratio (>2*ULN) | 0 participants |
| Bosutinib 50 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Calcium (<1.75 mmol/L) | 0 participants |
| Bosutinib 50 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Potassium (<3 mmol/L) | 0 participants |
| Bosutinib 50 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Alkaline phosphatase (>5*ULN) | 0 participants |
| Bosutinib 50 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Phosphorus (<0.6 mmol/L) | 0 participants |
| Bosutinib 50 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Prothrombin time (>2*ULN) | 0 participants |
| Bosutinib 50 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Glucose (<2.2 mmol/L) | 0 participants |
| Bosutinib 50 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Alanine aminotransferase (> 5*ULN) | 0 participants |
| Bosutinib 50 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Sodium (<130 mmol/L) | 0 participants |
| Bosutinib 50 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Aspartate aminotransferase (> 5*ULN)) | 0 participants |
| Bosutinib 50 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Creatinine (>3*ULN) | 0 participants |
| Bosutinib 50 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Partial thromboplastin time (>2*ULN) | 0 participants |
| Bosutinib 50 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Calcium (>3.1 mmol/L) | 0 participants |
| Bosutinib 50 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Albumin (<20 g/L) | 0 participants |
| Bosutinib 50 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Potassium (>6 mmol/L) | 0 participants |
| Bosutinib 100 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Alanine aminotransferase (> 5*ULN) | 0 participants |
| Bosutinib 100 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Aspartate aminotransferase (> 5*ULN)) | 0 participants |
| Bosutinib 100 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Alkaline phosphatase (>5*ULN) | 1 participants |
| Bosutinib 100 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Platelets (<50*10^9/L) | 1 participants |
| Bosutinib 100 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Bilirubin total (>3*ULN) | 0 participants |
| Bosutinib 100 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Albumin (<20 g/L) | 0 participants |
| Bosutinib 100 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Hemoglobin (<80 g/L) | 0 participants |
| Bosutinib 100 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Calcium (<1.75 mmol/L) | 0 participants |
| Bosutinib 100 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Calcium (>3.1 mmol/L) | 0 participants |
| Bosutinib 100 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Partial thromboplastin time (>2*ULN) | 0 participants |
| Bosutinib 100 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Creatinine (>3*ULN) | 0 participants |
| Bosutinib 100 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Glucose (<2.2 mmol/L) | 0 participants |
| Bosutinib 100 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Prothrombin time (>2*ULN) | 1 participants |
| Bosutinib 100 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Phosphorus (<0.6 mmol/L) | 0 participants |
| Bosutinib 100 mg | Number of Participants With Change From Baseline in Laboratory Test Results | International normalized ratio (>2*ULN) | 1 participants |
| Bosutinib 100 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Potassium (<3 mmol/L) | 1 participants |
| Bosutinib 100 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Potassium (>6 mmol/L) | 0 participants |
| Bosutinib 100 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Sodium (<130 mmol/L) | 0 participants |
| Bosutinib 200 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Partial thromboplastin time (>2*ULN) | 0 participants |
| Bosutinib 200 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Prothrombin time (>2*ULN) | 0 participants |
| Bosutinib 200 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Alanine aminotransferase (> 5*ULN) | 0 participants |
| Bosutinib 200 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Aspartate aminotransferase (> 5*ULN)) | 0 participants |
| Bosutinib 200 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Glucose (<2.2 mmol/L) | 0 participants |
| Bosutinib 200 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Bilirubin total (>3*ULN) | 0 participants |
| Bosutinib 200 mg | Number of Participants With Change From Baseline in Laboratory Test Results | International normalized ratio (>2*ULN) | 0 participants |
| Bosutinib 200 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Potassium (>6 mmol/L) | 0 participants |
| Bosutinib 200 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Sodium (<130 mmol/L) | 0 participants |
| Bosutinib 200 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Albumin (<20 g/L) | 0 participants |
| Bosutinib 200 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Phosphorus (<0.6 mmol/L) | 0 participants |
| Bosutinib 200 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Alkaline phosphatase (>5*ULN) | 0 participants |
| Bosutinib 200 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Calcium (<1.75 mmol/L) | 0 participants |
| Bosutinib 200 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Creatinine (>3*ULN) | 0 participants |
| Bosutinib 200 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Calcium (>3.1 mmol/L) | 0 participants |
| Bosutinib 200 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Hemoglobin (<80 g/L) | 0 participants |
| Bosutinib 200 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Potassium (<3 mmol/L) | 0 participants |
| Bosutinib 200 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Platelets (<50*10^9/L) | 0 participants |
| Bosutinib 300 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Bilirubin total (>3*ULN) | 0 participants |
| Bosutinib 300 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Partial thromboplastin time (>2*ULN) | 2 participants |
| Bosutinib 300 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Aspartate aminotransferase (> 5*ULN)) | 0 participants |
| Bosutinib 300 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Calcium (>3.1 mmol/L) | 0 participants |
| Bosutinib 300 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Albumin (<20 g/L) | 0 participants |
| Bosutinib 300 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Alkaline phosphatase (>5*ULN) | 0 participants |
| Bosutinib 300 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Sodium (<130 mmol/L) | 1 participants |
| Bosutinib 300 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Creatinine (>3*ULN) | 0 participants |
| Bosutinib 300 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Prothrombin time (>2*ULN) | 0 participants |
| Bosutinib 300 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Glucose (<2.2 mmol/L) | 0 participants |
| Bosutinib 300 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Alanine aminotransferase (> 5*ULN) | 0 participants |
| Bosutinib 300 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Potassium (>6 mmol/L) | 0 participants |
| Bosutinib 300 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Phosphorus (<0.6 mmol/L) | 1 participants |
| Bosutinib 300 mg | Number of Participants With Change From Baseline in Laboratory Test Results | International normalized ratio (>2*ULN) | 1 participants |
| Bosutinib 300 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Potassium (<3 mmol/L) | 0 participants |
| Bosutinib 300 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Hemoglobin (<80 g/L) | 0 participants |
| Bosutinib 300 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Platelets (<50*10^9/L) | 0 participants |
| Bosutinib 300 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Calcium (<1.75 mmol/L) | 0 participants |
| Bosutinib 400 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Glucose (<2.2 mmol/L) | 0 participants |
| Bosutinib 400 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Potassium (>6 mmol/L) | 0 participants |
| Bosutinib 400 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Aspartate aminotransferase (> 5*ULN)) | 0 participants |
| Bosutinib 400 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Prothrombin time (>2*ULN) | 2 participants |
| Bosutinib 400 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Albumin (<20 g/L) | 0 participants |
| Bosutinib 400 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Partial thromboplastin time (>2*ULN) | 0 participants |
| Bosutinib 400 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Bilirubin total (>3*ULN) | 0 participants |
| Bosutinib 400 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Hemoglobin (<80 g/L) | 0 participants |
| Bosutinib 400 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Calcium (<1.75 mmol/L) | 0 participants |
| Bosutinib 400 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Creatinine (>3*ULN) | 0 participants |
| Bosutinib 400 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Potassium (<3 mmol/L) | 0 participants |
| Bosutinib 400 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Alanine aminotransferase (> 5*ULN) | 0 participants |
| Bosutinib 400 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Sodium (<130 mmol/L) | 0 participants |
| Bosutinib 400 mg | Number of Participants With Change From Baseline in Laboratory Test Results | International normalized ratio (>2*ULN) | 2 participants |
| Bosutinib 400 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Alkaline phosphatase (>5*ULN) | 0 participants |
| Bosutinib 400 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Phosphorus (<0.6 mmol/L) | 1 participants |
| Bosutinib 400 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Platelets (<50*10^9/L) | 0 participants |
| Bosutinib 400 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Calcium (>3.1 mmol/L) | 0 participants |
| Bosutinib 500 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Glucose (<2.2 mmol/L) | 0 participants |
| Bosutinib 500 mg | Number of Participants With Change From Baseline in Laboratory Test Results | International normalized ratio (>2*ULN) | 0 participants |
| Bosutinib 500 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Albumin (<20 g/L) | 0 participants |
| Bosutinib 500 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Alkaline phosphatase (>5*ULN) | 1 participants |
| Bosutinib 500 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Bilirubin total (>3*ULN) | 0 participants |
| Bosutinib 500 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Calcium (<1.75 mmol/L) | 0 participants |
| Bosutinib 500 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Calcium (>3.1 mmol/L) | 0 participants |
| Bosutinib 500 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Creatinine (>3*ULN) | 0 participants |
| Bosutinib 500 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Phosphorus (<0.6 mmol/L) | 0 participants |
| Bosutinib 500 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Potassium (<3 mmol/L) | 0 participants |
| Bosutinib 500 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Potassium (>6 mmol/L) | 0 participants |
| Bosutinib 500 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Aspartate aminotransferase (> 5*ULN)) | 1 participants |
| Bosutinib 500 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Alanine aminotransferase (> 5*ULN) | 1 participants |
| Bosutinib 500 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Sodium (<130 mmol/L) | 1 participants |
| Bosutinib 500 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Prothrombin time (>2*ULN) | 0 participants |
| Bosutinib 500 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Partial thromboplastin time (>2*ULN) | 0 participants |
| Bosutinib 500 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Hemoglobin (<80 g/L) | 0 participants |
| Bosutinib 500 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Platelets (<50*10^9/L) | 0 participants |
| Bosutinib 600 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Albumin (<20 g/L) | 0 participants |
| Bosutinib 600 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Glucose (<2.2 mmol/L) | 0 participants |
| Bosutinib 600 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Partial thromboplastin time (>2*ULN) | 1 participants |
| Bosutinib 600 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Sodium (<130 mmol/L) | 0 participants |
| Bosutinib 600 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Creatinine (>3*ULN) | 0 participants |
| Bosutinib 600 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Platelets (<50*10^9/L) | 0 participants |
| Bosutinib 600 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Prothrombin time (>2*ULN) | 0 participants |
| Bosutinib 600 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Potassium (>6 mmol/L) | 0 participants |
| Bosutinib 600 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Calcium (>3.1 mmol/L) | 0 participants |
| Bosutinib 600 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Alkaline phosphatase (>5*ULN) | 0 participants |
| Bosutinib 600 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Potassium (<3 mmol/L) | 1 participants |
| Bosutinib 600 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Hemoglobin (<80 g/L) | 0 participants |
| Bosutinib 600 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Aspartate aminotransferase (> 5*ULN)) | 0 participants |
| Bosutinib 600 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Phosphorus (<0.6 mmol/L) | 0 participants |
| Bosutinib 600 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Bilirubin total (>3*ULN) | 1 participants |
| Bosutinib 600 mg | Number of Participants With Change From Baseline in Laboratory Test Results | International normalized ratio (>2*ULN) | 0 participants |
| Bosutinib 600 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Alanine aminotransferase (> 5*ULN) | 0 participants |
| Bosutinib 600 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Calcium (<1.75 mmol/L) | 0 participants |
| MTD-lead in | Number of Participants With Change From Baseline in Laboratory Test Results | Platelets (<50*10^9/L) | 1 participants |
| MTD-lead in | Number of Participants With Change From Baseline in Laboratory Test Results | Potassium (>6 mmol/L) | 0 participants |
| MTD-lead in | Number of Participants With Change From Baseline in Laboratory Test Results | Potassium (<3 mmol/L) | 0 participants |
| MTD-lead in | Number of Participants With Change From Baseline in Laboratory Test Results | Sodium (<130 mmol/L) | 0 participants |
| MTD-lead in | Number of Participants With Change From Baseline in Laboratory Test Results | Phosphorus (<0.6 mmol/L) | 0 participants |
| MTD-lead in | Number of Participants With Change From Baseline in Laboratory Test Results | International normalized ratio (>2*ULN) | 1 participants |
| MTD-lead in | Number of Participants With Change From Baseline in Laboratory Test Results | Glucose (<2.2 mmol/L) | 0 participants |
| MTD-lead in | Number of Participants With Change From Baseline in Laboratory Test Results | Creatinine (>3*ULN) | 0 participants |
| MTD-lead in | Number of Participants With Change From Baseline in Laboratory Test Results | Prothrombin time (>2*ULN) | 0 participants |
| MTD-lead in | Number of Participants With Change From Baseline in Laboratory Test Results | Calcium (>3.1 mmol/L) | 0 participants |
| MTD-lead in | Number of Participants With Change From Baseline in Laboratory Test Results | Calcium (<1.75 mmol/L) | 0 participants |
| MTD-lead in | Number of Participants With Change From Baseline in Laboratory Test Results | Partial thromboplastin time (>2*ULN) | 1 participants |
| MTD-lead in | Number of Participants With Change From Baseline in Laboratory Test Results | Bilirubin total (>3*ULN) | 0 participants |
| MTD-lead in | Number of Participants With Change From Baseline in Laboratory Test Results | Hemoglobin (<80 g/L) | 0 participants |
| MTD-lead in | Number of Participants With Change From Baseline in Laboratory Test Results | Alkaline phosphatase (>5*ULN) | 0 participants |
| MTD-lead in | Number of Participants With Change From Baseline in Laboratory Test Results | Aspartate aminotransferase (> 5*ULN)) | 0 participants |
| MTD-lead in | Number of Participants With Change From Baseline in Laboratory Test Results | Albumin (<20 g/L) | 0 participants |
| MTD-lead in | Number of Participants With Change From Baseline in Laboratory Test Results | Alanine aminotransferase (> 5*ULN) | 0 participants |
| RP2D 400 mg | Number of Participants With Change From Baseline in Laboratory Test Results | International normalized ratio (>2*ULN) | 6 participants |
| RP2D 400 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Bilirubin total (>3*ULN) | 2 participants |
| RP2D 400 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Aspartate aminotransferase (> 5*ULN)) | 5 participants |
| RP2D 400 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Glucose (<2.2 mmol/L) | 2 participants |
| RP2D 400 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Alkaline phosphatase (>5*ULN) | 5 participants |
| RP2D 400 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Alanine aminotransferase (> 5*ULN) | 5 participants |
| RP2D 400 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Phosphorus (<0.6 mmol/L) | 0 participants |
| RP2D 400 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Potassium (>6 mmol/L) | 1 participants |
| RP2D 400 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Hemoglobin (<80 g/L) | 3 participants |
| RP2D 400 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Calcium (>3.1 mmol/L) | 1 participants |
| RP2D 400 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Potassium (<3 mmol/L) | 1 participants |
| RP2D 400 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Prothrombin time (>2*ULN) | 7 participants |
| RP2D 400 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Calcium (<1.75 mmol/L) | 1 participants |
| RP2D 400 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Sodium (<130 mmol/L) | 7 participants |
| RP2D 400 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Platelets (<50*10^9/L) | 0 participants |
| RP2D 400 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Creatinine (>3*ULN) | 2 participants |
| RP2D 400 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Albumin (<20 g/L) | 1 participants |
| RP2D 400 mg | Number of Participants With Change From Baseline in Laboratory Test Results | Partial thromboplastin time (>2*ULN) | 1 participants |
Secondary
Number of Participants With Change From Baseline in Opthalmologic Examination
Ophthalmologic evaluation included visual acuity, funduscopic examination, and any clinically-significant abnormality.
Time frame: Baseline up to end of treatment (Week 95)
Population: Safety population included all participants who had taken at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bosutinib 50 mg | Number of Participants With Change From Baseline in Opthalmologic Examination | 0 participants |
| Bosutinib 100 mg | Number of Participants With Change From Baseline in Opthalmologic Examination | 0 participants |
| Bosutinib 200 mg | Number of Participants With Change From Baseline in Opthalmologic Examination | 0 participants |
| Bosutinib 300 mg | Number of Participants With Change From Baseline in Opthalmologic Examination | 1 participants |
| Bosutinib 400 mg | Number of Participants With Change From Baseline in Opthalmologic Examination | 0 participants |
| Bosutinib 500 mg | Number of Participants With Change From Baseline in Opthalmologic Examination | 0 participants |
| Bosutinib 600 mg | Number of Participants With Change From Baseline in Opthalmologic Examination | 0 participants |
| MTD-lead in | Number of Participants With Change From Baseline in Opthalmologic Examination | 0 participants |
| RP2D 400 mg | Number of Participants With Change From Baseline in Opthalmologic Examination | 4 participants |
Secondary
Number of Participants With Change From Baseline in Physical Examination
Physical examinations included body weight, height and vital signs and only finding that exceeded the criterion for PCS was weight. Criteria for weight was: an increase or decrease of \>=10% from baseline.
Time frame: Baseline up to end of treatment (Week 95)
Population: Safety population included all participants who had taken at least 1 dose of study medication. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable (at least 1 on-therapy assessment) for this measure for each group respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bosutinib 50 mg | Number of Participants With Change From Baseline in Physical Examination | Weight (decrease >=10%) | 0 participants |
| Bosutinib 50 mg | Number of Participants With Change From Baseline in Physical Examination | Weight (increase >=10%) | 1 participants |
| Bosutinib 100 mg | Number of Participants With Change From Baseline in Physical Examination | Weight (decrease >=10%) | 0 participants |
| Bosutinib 100 mg | Number of Participants With Change From Baseline in Physical Examination | Weight (increase >=10%) | 1 participants |
| Bosutinib 200 mg | Number of Participants With Change From Baseline in Physical Examination | Weight (decrease >=10%) | 2 participants |
| Bosutinib 200 mg | Number of Participants With Change From Baseline in Physical Examination | Weight (increase >=10%) | 0 participants |
| Bosutinib 300 mg | Number of Participants With Change From Baseline in Physical Examination | Weight (decrease >=10%) | 2 participants |
| Bosutinib 300 mg | Number of Participants With Change From Baseline in Physical Examination | Weight (increase >=10%) | 1 participants |
| Bosutinib 400 mg | Number of Participants With Change From Baseline in Physical Examination | Weight (decrease >=10%) | 0 participants |
| Bosutinib 400 mg | Number of Participants With Change From Baseline in Physical Examination | Weight (increase >=10%) | 0 participants |
| Bosutinib 500 mg | Number of Participants With Change From Baseline in Physical Examination | Weight (increase >=10%) | 1 participants |
| Bosutinib 500 mg | Number of Participants With Change From Baseline in Physical Examination | Weight (decrease >=10%) | 0 participants |
| Bosutinib 600 mg | Number of Participants With Change From Baseline in Physical Examination | Weight (increase >=10%) | 1 participants |
| Bosutinib 600 mg | Number of Participants With Change From Baseline in Physical Examination | Weight (decrease >=10%) | 0 participants |
| MTD-lead in | Number of Participants With Change From Baseline in Physical Examination | Weight (decrease >=10%) | 0 participants |
| MTD-lead in | Number of Participants With Change From Baseline in Physical Examination | Weight (increase >=10%) | 0 participants |
| RP2D 400 mg | Number of Participants With Change From Baseline in Physical Examination | Weight (decrease >=10%) | 3 participants |
| RP2D 400 mg | Number of Participants With Change From Baseline in Physical Examination | Weight (increase >=10%) | 3 participants |
Secondary
Overall Survival (OS) in Part 2
Time in weeks from the start of study treatment to date of death due to any cause. OS was calculated as (the death date minus the date of first dose of study medication plus 1) divided by 7. Death was determined from death case report forms (CRFs) or from follow-up contact data (where the participant current status was death).
Time frame: Part 2 Baseline until death or 3, 6, 9 and 12 months after treatment discontinuation
Population: Efficacy evaluable population: participants who received at least 1 cycle (15 doses) of study medication, had no eligibility violations, did not use prohibited anti-cancer treatment, had baseline disease assessment, at least 1 disease assessment post-baseline/had experienced clinical progression/death before first post-baseline disease assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bosutinib 50 mg | Overall Survival (OS) in Part 2 | 27.7 weeks |
| Bosutinib 100 mg | Overall Survival (OS) in Part 2 | 14.7 weeks |
| Bosutinib 200 mg | Overall Survival (OS) in Part 2 | 34.0 weeks |
Secondary
Plasma Decay Half-Life (t1/2)
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Time frame: 0 hour (pre-dose) on Day 1, 0 (pre-dose), 1, 2, 3, 4, 6, 8, 24 (0 hour [pre-dose] on Day 15) hours post-dose on Day 14
Population: Analysis population included all participants who had taken at least 1 dose of study medication. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure and 'n' signifies those participants evaluable for specific time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Bosutinib 50 mg | Plasma Decay Half-Life (t1/2) | Day 1 (n = 3, 4, 6, 7, 47, 13, 10) | 12.86 hours | Standard Deviation 7.36 |
| Bosutinib 50 mg | Plasma Decay Half-Life (t1/2) | Day 15 (n = 3, 4, 5, 4, 53, 9, 2) | 25.84 hours | Standard Deviation 12.26 |
| Bosutinib 100 mg | Plasma Decay Half-Life (t1/2) | Day 1 (n = 3, 4, 6, 7, 47, 13, 10) | 18.61 hours | Standard Deviation 4.91 |
| Bosutinib 100 mg | Plasma Decay Half-Life (t1/2) | Day 15 (n = 3, 4, 5, 4, 53, 9, 2) | 64.65 hours | Standard Deviation 67.31 |
| Bosutinib 200 mg | Plasma Decay Half-Life (t1/2) | Day 1 (n = 3, 4, 6, 7, 47, 13, 10) | 20.80 hours | Standard Deviation 6.07 |
| Bosutinib 200 mg | Plasma Decay Half-Life (t1/2) | Day 15 (n = 3, 4, 5, 4, 53, 9, 2) | 30.04 hours | Standard Deviation 20.13 |
| Bosutinib 300 mg | Plasma Decay Half-Life (t1/2) | Day 1 (n = 3, 4, 6, 7, 47, 13, 10) | 17.12 hours | Standard Deviation 6.01 |
| Bosutinib 300 mg | Plasma Decay Half-Life (t1/2) | Day 15 (n = 3, 4, 5, 4, 53, 9, 2) | 19.35 hours | Standard Deviation 7.54 |
| Bosutinib 400 mg | Plasma Decay Half-Life (t1/2) | Day 1 (n = 3, 4, 6, 7, 47, 13, 10) | 18.63 hours | Standard Deviation 7.67 |
| Bosutinib 400 mg | Plasma Decay Half-Life (t1/2) | Day 15 (n = 3, 4, 5, 4, 53, 9, 2) | 19.89 hours | Standard Deviation 16.72 |
| Bosutinib 500 mg | Plasma Decay Half-Life (t1/2) | Day 1 (n = 3, 4, 6, 7, 47, 13, 10) | 21.87 hours | Standard Deviation 7.39 |
| Bosutinib 500 mg | Plasma Decay Half-Life (t1/2) | Day 15 (n = 3, 4, 5, 4, 53, 9, 2) | 23.25 hours | Standard Deviation 15 |
| Bosutinib 600 mg | Plasma Decay Half-Life (t1/2) | Day 1 (n = 3, 4, 6, 7, 47, 13, 10) | 19.94 hours | Standard Deviation 5.47 |
| Bosutinib 600 mg | Plasma Decay Half-Life (t1/2) | Day 15 (n = 3, 4, 5, 4, 53, 9, 2) | 16.29 hours | — |
Secondary
Progression Free Survival (PFS) in Part 2
Time in weeks from start of study treatment to first documentation of objective tumor progression or death due to any cause. PFS was calculated as (first event date minus the date of first dose of study medication plus 1) divided by 7. Tumor progression was determined from oncologic assessment data (where data meet the criteria for PD, or from death CRFs).
Time frame: Part 2 Baseline until death or 3, 6, 9 and 12 months after treatment discontinuation
Population: Efficacy evaluable population: participants who received at least 1 cycle (15 doses) of study medication, had no eligibility violations, did not use prohibited anti-cancer treatment, had baseline disease assessment, at least 1 disease assessment post-baseline/had experienced clinical progression/death before first post-baseline disease assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bosutinib 50 mg | Progression Free Survival (PFS) in Part 2 | 6.0 weeks |
| Bosutinib 100 mg | Progression Free Survival (PFS) in Part 2 | 6.0 weeks |
| Bosutinib 200 mg | Progression Free Survival (PFS) in Part 2 | 5.7 weeks |
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Time frame: 0 hour (pre-dose) on Day 1, 0 (pre-dose), 1, 2, 3, 4, 6, 8, 24 (0 hour [pre-dose] on Day 15) hours post-dose on Day 14
Population: Analysis population included all participants who had taken at least one dose of study medication. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure and 'n' signifies those participants evaluable for specific time points.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Bosutinib 50 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) | Day 1 (n = 4, 4, 6, 7, 54, 13, 10) | 6.01 hours |
| Bosutinib 50 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) | Day 15 (n = 3, 4, 5, 5, 69, 10, 2) | 4.00 hours |
| Bosutinib 100 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) | Day 1 (n = 4, 4, 6, 7, 54, 13, 10) | 4.08 hours |
| Bosutinib 100 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) | Day 15 (n = 3, 4, 5, 5, 69, 10, 2) | 3.50 hours |
| Bosutinib 200 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) | Day 1 (n = 4, 4, 6, 7, 54, 13, 10) | 6.00 hours |
| Bosutinib 200 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) | Day 15 (n = 3, 4, 5, 5, 69, 10, 2) | 4.00 hours |
| Bosutinib 300 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) | Day 1 (n = 4, 4, 6, 7, 54, 13, 10) | 6.00 hours |
| Bosutinib 300 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) | Day 15 (n = 3, 4, 5, 5, 69, 10, 2) | 4.02 hours |
| Bosutinib 400 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) | Day 1 (n = 4, 4, 6, 7, 54, 13, 10) | 4.00 hours |
| Bosutinib 400 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) | Day 15 (n = 3, 4, 5, 5, 69, 10, 2) | 4.00 hours |
| Bosutinib 500 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) | Day 1 (n = 4, 4, 6, 7, 54, 13, 10) | 4.00 hours |
| Bosutinib 500 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) | Day 15 (n = 3, 4, 5, 5, 69, 10, 2) | 5.00 hours |
| Bosutinib 600 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) | Day 1 (n = 4, 4, 6, 7, 54, 13, 10) | 6.00 hours |
| Bosutinib 600 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) | Day 15 (n = 3, 4, 5, 5, 69, 10, 2) | 3.53 hours |
Other Pre-specified
Gene Expression at Baseline
Gene expression profile was evaluated by measuring transcript levels of messenger RNA (mRNA) in peripheral blood samples. Expression profiling of mRNA: done to measure the expressed genome of mRNA transcripts or done in a gene-specific targeted manner.
Time frame: Baseline
Population: Data was not analyzed as the analysis was cancelled due to lack of samples provided from sites.