Advanced Solid Tumors
Conditions
Keywords
Drug therapy
Brief summary
The purposes of this study were to estimate the relative (Rel) bioavailability (BA) of an oral solution (OS) formulation of alisertib in reference to a powder-in-capsule (PIC) formulation, to characterize the effect of food on the single-dose pharmacokinetics (PK) of alisertib OS and enteric-coated tablets (ECT), to characterize the multiple-dose safety, tolerability, and steady-state PK of alisertib administered as an OS, and to characterize the multiple-dose safety and tolerability of alisertib administered as an ECT.
Detailed description
The drug being tested in this study is called alisertib (MLN8237). Alisertib is being tested to treat people who have advanced solid tumors. This study will look at the relative bioavailability (BA) (Part A), food effect and multiple-dose PK and safety of the oral solution (OS) (Part B) and food effect and safety of the enteric-coated tablet (ECT) formulation (Part C). The study enrolled 53 patients (pts). Prior to initiation of Part A, 4 participants were enrolled in a dose escalation cohort. Participants in the study received: • Alisertib 15 mg to 50 mg orally In the first 2 cycles of all 3 parts of the study, a single dose of alisertib was administered on Day 1 (PIC or OS in Part A \[n=19 pts\]; OS, in the fed or fasted state, in Part B \[n=6 pts\]; ECT, in the fed or fasted state, in Part C \[n=24 pts\]), In Part A, participants then continued on the PIC formulation at 40 mg BID for 7 days (Days 3 - 9). In Part B, participants continued on the OS formulation at a calculated dose administered BID for 7 days (Days 3 - 9). In Part C, the ECT formulation was continued at 40 mg BID for 7 days (Days 3 - 9); however, dose escalation to 50 mg BID was permitted after Cycle 1 based on tolerability and safety findings in the prior cycles. All participants took doses at a gap of 12 hours each day for 7 days followed by a 14-day rest period in a 21-days cycle for the remaining cycles. This multi-center trial was conducted in the United States. The overall time to participate in this study was 30 months. Participants made multiple visits to the clinic, and final assessments were performed approximately 30 days after last dose of study drug.
Interventions
DRUGAlisertib
Alisertib OS Alisertib PIC Alisertib PIC
Sponsors
Millennium Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Each participant must meet all of the following inclusion criteria to be enrolled in the study: * 18 years or older * Histologically or cytologically confirmed metastatic and/or advanced solid tumor * Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 * Female participants who are post menopausal, surgically sterile, or agree to practice 2 effective methods of contraception or abstain from heterosexual intercourse * Male participants who agree to practice effective barrier contraception or agree to abstain from heterosexual intercourse * Voluntary written consent * Suitable venous access for study-required blood sampling * Measurable disease * Recovered from effects of prior antineoplastic therapy * Meet required entry laboratory and organ function levels
Exclusion criteria
Participants meeting any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Abnormal Vital Signs Reported as Adverse Events | Up to 30 days after the last dose of study drug (up to 24 months approximately) | Vital signs (blood pressure, heart rate, and oral temperature) measurements were obtained throughout the study. |
| Part A: Dose-normalized Cmax (Maximum Observed Concentration) for Estimation of Relative Bioavailability for Alisertib Oral Solution (OS) Versus Powder in Capsule Formulations (PIC) | Cycles 1 and 2 Day 1 predose and at multiple time points (up to 48 hours) postdose, and, if clinically feasible, at the time of a serious or unusual adverse event (AE) that was judged by the investigator to be treatment related. | Dose normalized Cmax was obtained using Cmax divided by alisertib dose in milligrams to provide values adjusted to a 1 mg alisertib dose. |
| Part A: Dose-normalized AUClast (Area Under the Concentration-Time Curve From Time 0 to Time of the Last Quantifiable Concentration) for Estimation of Relative Bioavailability for Alisertib Oral Solution (OS) Versus Powder in Capsule Formulations (PIC) | Cycles 1 and 2 Day 1 predose and at multiple time points (up to 48 hours) postdose, and, if clinically feasible, at the time of a serious or unusual AE that was judged by the investigator to be treatment related. | Dose normalized AUClast was obtained using Cmax divided by alisertib dose in milligrams to provide values adjusted to a 1 mg alisertib dose. |
| Part B: Cmax: Maximum Observed Concentration for Alisertib Administered as an Oral Solution With Food Versus Without Food | Cycles 1 and 2 Day 1 predose and at multiple time points (up to 48 hours) postdose, and, if clinically feasible, at the time of a serious or unusual AE that was judged by the investigator to be treatment related. | Not performed. |
| Part B: AUClast: Area Under the Concentration-Time Curve From Time 0 to Time of the Last Quantifiable Concentration for Alisertib Administered as an Oral Solution With Food Versus Without Food | Cycles 1 and 2 Day 1 predose and at multiple time points (up to 48 hours) postdose, and, if clinically feasible, at the time of a serious or unusual AE that was judged by the investigator to be treatment related. | Not performed. |
| Part B: Cmax: Maximum Plasma Concentration for Alisertib Oral Solution Following Multiple-Dose Administration | Cycle 1 Day 9 predose and at multiple time points (up to 12 hours) postdose, and, if clinically feasible, at the time of a serious or unusual AE that was judged by the investigator to be treatment related. | Not performed. |
| Part B: Tmax: Time of First Occurrence of Cmax Over the Dosing Interval for Alisertib Oral Solution Following Multiple-Dose Administration | Cycle 1 Day 9 predose and at multiple time points (up to 12 hours) postdose, and, if clinically feasible, at the time of a serious or unusual AE that was judged by the investigator to be treatment related. | Not performed. |
| Part B: AUCτ: Area Under the Concentration-Time Curve From Time 0 to End of Dosing Interval for Alisertib Oral Solution Following Multiple-Dose Administration | Cycle 1 Day 9 predose and at multiple time points (up to 12 hours) postdose, and, if clinically feasible, at the time of a serious or unusual AE that was judged by the investigator to be treatment related. | Not performed. |
| Part C: Cmax: Maximum Observed Concentration for Alisertib Administered as an Enteric-Coated Capsule (ECT) With Food Versus Without Food | Cycles 1 and 2 Day 1 predose and at multiple time points (up to 48 hours) postdose, and, if clinically feasible, at the time of a serious or unusual AE that was judged by the investigator to be treatment related. | Participants were randomized to receive 50-mg alisertib as an ECT (single, 50-mg strength tablets) under fasted or fed (following a standardized high-fat meal) conditions. |
| Part C: AUClast: Area Under the Concentration-Time Curve From Time 0 to Time of the Last Quantifiable Concentration for Alisertib Administered as an Enteric-Coated Capsule (ECT) With Food Versus Without Food | Cycles 1 and 2 on Day 1 predose and at multiple time points (up to 48 hours) postdose, and, if clinically feasible, at the time of a serious or unusual AE that was judged by the investigator to be treatment related. | — |
| Part C: AUC∞: Area Under the Concentration-Time Curve From Time 0 to Infinity, Calculated Using the Observed Value of the Last Quantifiable Concentration for Alisertib Administered as an Enteric-Coated Capsule (ECT) With Food Versus Without Food | Cycles 1 and 2 on Day 1 predose and at multiple time points (up to 48 hours) postdose, and, if clinically feasible, at the time of a serious or unusual AE that was judged by the investigator to be treatment related. | — |
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Up to 30 days after the last dose of study drug (up to 27.4 months) | An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A Serious Adverse Event (SAE) A serious is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant. |
| Number of Participants With Abnormal Laboratory Values Reported as Adverse Events at an Incidence of at Least 5% | Up to 30 days after the last dose of study drug (up to 27.4 months) | Laboratory AEs reported at an incidence of at least 5% overall in the following system organ classes (SOCs) are reported: blood and lymphatic system disorders, metabolism and nutrition disorders, investigations, and hepatobiliary disorders. Abnormal laboratory value were assessed as an AE if the value leads to discontinuation or delay in treatment, dose modification, therapeutic intervention, or is considered by the investigator to be a clinically significant change from baseline. A treatment--emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Best Overall Response (CR+PR) Based on Investigator's Assessment According to the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | At the completion of Cycle 2 and every 2 cycles (every 6 weeks) until Cycle 6 (18 weeks). After Cycle 6 (18 weeks), CT/MRI scans (with contrast) were to be performed every 3 cycles (9 weeks) until PD was documented. | Best overall response is defined as the number of participants with Complete Response (CR) + Partial Response (PR) as assessed by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.1 for target lesions and assessed by CT or MRI. CR is defined as disappearance of all target lesions and PR is defined as 30% decrease in the sum of the longest diameter (LD) of target lesions. Stable Disease (SD) is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Progressive Disease, taking as reference the smallest sum LD since the treatment started. |
Countries
United States
Participant flow
Recruitment details
Participants took part in the study at 3 investigative sites in the United States from 25 September 2009 to 01 July 2014.
Pre-assignment details
Participants with a diagnosis of advanced solid tumors were enrolled to receive alisertib in 1 of 4 parts: Dose Escalation, Part A (relative bioavailability), Part B (food effect and multiple-dose pharmacokinetics of alisertib oral solution \[OS\]), and Part C (food effect and safety of alisertib enteric-coated tablets \[ECT\]).
Participants by arm
| Arm | Count |
|---|---|
| Dose Escalation Cohort A single dose of alisertib 15 mg, oral solution (OS) was administered on Day 1, followed by alisertib 40 mg, powder-in-capsule (PIC), orally, twice a day (BID) on Days 3 through 9, followed by a 14-day rest period in Cycle 1 in a 23-day cycle. A single dose of alisertib 50 mg PIC, orally, was administered on Cycle 2 Day 1 followed by alisertib 40 mg on Days 3 through 9, followed by a 14-day rest period in Cycle 2 in a 23-day cycle. Subsequent cycles, alisertib 40 or 50 mg (individual dosage based on tolerability in Cycles 1 and 2), PIC, orally, BID on Days 1 through 7, followed by a 14-day rest period in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy. | 4 |
| Part A: Relative Bioavailability OS/PIC (Sequence A) A single dose of alisertib 25 mg, OS, administered on Day 1, followed by alisertib 40 mg PIC, orally, BID on Days 3 through 9, followed by a 14-day rest period in Cycle 1, in a 23-day cycle. A single dose of alisertib 50 mg PIC, orally, administered on Cycle 2 Day 1, followed by alisertib 40 mg, PIC, orally, BID on Days 3 through 9, followed by a 14-day rest period in a 23-day cycle. Subsequent cycles, alisertib 40-50 mg (individual dosage based on tolerability in Cycles 1 and 2), PIC, orally, BID on Days 1 through 7, followed by a 14-day rest period in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy. | 9 |
| Part A: Relative Bioavailability PIC/OS (Sequence B) A single dose of alisertib 50 mg, PIC, orally administered on Day 1, followed by alisertib 40 mg, PIC, orally, BID on Days 3 through 9, followed by a 14-day rest period in Cycle 1, in a 23-day cycle. Cycle 2 Day 1 alisertib 25 mg, OS, once on Day 1, followed by alisertib 40 mg, PIC, orally, BID on Days 3 through 9, followed by a 14-day rest period in a 23-day cycle. Subsequent cycles followed by alisertib 40-50 mg (individual dosage based on tolerability in Cycles 1 and 2), PIC, orally, BID on Days 1 through 7, followed by a 14-day rest period in Cycle 3, in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy. | 10 |
| Part B: OS Food Effect Fed/Fasted (Sequence A) Alisertib 35 mg (35 mg = relative bioavailability estimate in Part A as dose of OS that was calculated to yield the area under the concentration time curve of a 50-mg PIC dose): A single dose of alisertib 35 mg oral solution (OS), in fed state, administered on Day 1, followed by alisertib 30 mg, OS, BID on Days 3-9, followed by a 14-day rest period in Cycle 1, in a 23-day cycle. Cycle 2 Day 1 alisertib 35 mg administered, OS, in fasted state, once on Day 1, followed by alisertib 30 mg, OS, BID on Days 3-9, followed by a 14-day rest period in a 23-day cycle. Cycle 3 onwards, participants received alisertib 40 mg, PIC, orally, BID on Days 1-7, with dose reduction to 30 mg BID or escalation to 50 mg BID permitted, based on individual tolerance, followed by a 14-day rest period, in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy. | 3 |
| Part B: OS Food Effect Fasted/Fed (Sequence B) A single dose of alisertib 35 mg, OS, in fasted state, administered on Day 1, followed by alisertib 30 mg, OS, BID on Days 3-9, followed by a 14-day rest period in a 23-day cycle. Cycle 2 Day 1 alisertib 30 mg, OS administered in fed state, once on Day 1, followed by alisertib 30 mg, OS, BID on Days 3-9, followed by a 14-day rest period in a 23-day cycle. Cycle 3 onwards, participants received alisertib 40 mg PIC, orally, BID on Days 1-7, with dose reduction to 30 mg BID or escalation to 50 mg BID permitted based on individual tolerance, followed by a 14-day rest period in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy. | 3 |
| Part C: ECT Food Effect Fed/Fasted (Sequence A) Alisertib 50 mg, enteric-coated tablets (ECT), orally, in fed state, once on Day 1, followed by alisertib 40 mg, ECT, orally, BID on Days 3 through 9, followed by a 14-day rest period in Cycle 1 in a 23-day cycle, followed by alisertib 50 mg, ECT, orally, in fasted state, once on Day 1, followed by alisertib 40 or 50 mg, ECT, orally, BID on Days 3 through 9, followed by a 14-day rest period in Cycle 2 in a 23-day cycle. Cycle 3 onwards, participants were administered alisertib 40 mg BID ECT on Days 1-7 with dose reduction to 30 mg BID or escalation to 50 mg BID permitted based on individual tolerance, followed by a 14-day rest period in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy. | 12 |
| Part C: ECT Food Effect Fasted/Fed (Sequence B) Alisertib 50 mg, ECT, orally, in fasted state, once on Day 1, followed by alisertib 40 mg, ECT, BID on Days 3 through 9, followed by a 14-day rest period in Cycle 1 in a 23-day cycle, followed by alisertib 50 mg, ECT, orally, in fed state, once on Day 1, followed by alisertib 40 or 50 mg, ECT, orally, BID on Days 3 through 9, followed by a 14-day rest period in Cycle 2, a 23-day cycle. Cycle 3 onwards participants were administered alisertib 40 mg BID ECT on Days 1-7, with dose reduction to 30 mg BID or escalation to 50 mg BID permitted based on individual tolerance, followed by a 14-day rest period, in 21-day cycles until disease progression, occurrence of an unacceptable alisertib-related toxicity, or the start of another anticancer therapy. | 12 |
| Total | 53 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 2 | 1 | 1 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Dose Escalation Cohort | Total | Part C: ECT Food Effect Fasted/Fed (Sequence B) | Part C: ECT Food Effect Fed/Fasted (Sequence A) | Part B: OS Food Effect Fasted/Fed (Sequence B) | Part B: OS Food Effect Fed/Fasted (Sequence A) | Part A: Relative Bioavailability PIC/OS (Sequence B) | Part A: Relative Bioavailability OS/PIC (Sequence A) |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 58.3 years | 55.5 years | 55.2 years | 57.4 years | 57.7 years | 51.7 years | 54.0 years | 54.6 years |
| Body Surface Area (BSA) | 1.84 m^2 | 1.85 m^2 | 1.68 m^2 | 1.82 m^2 | 1.90 m^2 | 1.69 m^2 | 1.97 m^2 | 2.02 m^2 |
| Height | 167.7 cm | 167.4 cm | 160.5 cm | 169.2 cm | 169.1 cm | 160.3 cm | 172.8 cm | 172.6 cm |
| Race/Ethnicity, Customized Asian | 0 participants | 1 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Black or African American | 0 participants | 3 participants | 1 participants | 0 participants | 1 participants | 0 participants | 1 participants | 0 participants |
| Race/Ethnicity, Customized Hispanic or Latino | 0 participants | 6 participants | 1 participants | 2 participants | 1 participants | 0 participants | 2 participants | 0 participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 4 participants | 47 participants | 11 participants | 10 participants | 2 participants | 3 participants | 8 participants | 9 participants |
| Race/Ethnicity, Customized White | 4 participants | 49 participants | 11 participants | 12 participants | 2 participants | 3 participants | 9 participants | 8 participants |
| Region of Enrollment United States | 4 participants | 53 participants | 12 participants | 12 participants | 3 participants | 3 participants | 10 participants | 9 participants |
| Sex: Female, Male Female | 3 Participants | 28 Participants | 9 Participants | 7 Participants | 1 Participants | 1 Participants | 5 Participants | 2 Participants |
| Sex: Female, Male Male | 1 Participants | 25 Participants | 3 Participants | 5 Participants | 2 Participants | 2 Participants | 5 Participants | 7 Participants |
| Weight | 72.7 kg | 74.7 kg | 66.1 kg | 73.0 kg | 77.7 kg | 66.3 kg | 81.4 kg | 85.5 kg |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 4 / 4 | 19 / 19 | 6 / 6 | 24 / 24 |
| serious Total, serious adverse events | 2 / 4 | 4 / 19 | 2 / 6 | 11 / 24 |
Outcome results
Primary
Number of Participants With Abnormal Laboratory Values Reported as Adverse Events at an Incidence of at Least 5%
Laboratory AEs reported at an incidence of at least 5% overall in the following system organ classes (SOCs) are reported: blood and lymphatic system disorders, metabolism and nutrition disorders, investigations, and hepatobiliary disorders. Abnormal laboratory value were assessed as an AE if the value leads to discontinuation or delay in treatment, dose modification, therapeutic intervention, or is considered by the investigator to be a clinically significant change from baseline. A treatment--emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.
Time frame: Up to 30 days after the last dose of study drug (up to 27.4 months)
Population: Safety Population is defined as all participants who receive any amount of alisertib.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A: Alisertib OS | Number of Participants With Abnormal Laboratory Values Reported as Adverse Events at an Incidence of at Least 5% | White blood cell count decreased | 0 participants |
| Part A: Alisertib OS | Number of Participants With Abnormal Laboratory Values Reported as Adverse Events at an Incidence of at Least 5% | Hypokalaemia | 0 participants |
| Part A: Alisertib OS | Number of Participants With Abnormal Laboratory Values Reported as Adverse Events at an Incidence of at Least 5% | Lymphopenia | 0 participants |
| Part A: Alisertib OS | Number of Participants With Abnormal Laboratory Values Reported as Adverse Events at an Incidence of at Least 5% | Hyperbilirubinaemia | 1 participants |
| Part A: Alisertib OS | Number of Participants With Abnormal Laboratory Values Reported as Adverse Events at an Incidence of at Least 5% | Hyperglycaemia | 0 participants |
| Part A: Alisertib OS | Number of Participants With Abnormal Laboratory Values Reported as Adverse Events at an Incidence of at Least 5% | Hypomagnesaemia | 0 participants |
| Part A: Alisertib OS | Number of Participants With Abnormal Laboratory Values Reported as Adverse Events at an Incidence of at Least 5% | Lymphocyte count decreased | 0 participants |
| Part A: Alisertib OS | Number of Participants With Abnormal Laboratory Values Reported as Adverse Events at an Incidence of at Least 5% | Neutropenia | 3 participants |
| Part A: Alisertib OS | Number of Participants With Abnormal Laboratory Values Reported as Adverse Events at an Incidence of at Least 5% | Anaemia | 3 participants |
| Part A: Alisertib OS | Number of Participants With Abnormal Laboratory Values Reported as Adverse Events at an Incidence of at Least 5% | Neutrophil count decreased | 0 participants |
| Part A: Alisertib OS | Number of Participants With Abnormal Laboratory Values Reported as Adverse Events at an Incidence of at Least 5% | Gamma-glutamyltransferase increased | 0 participants |
| Part A: Alisertib OS | Number of Participants With Abnormal Laboratory Values Reported as Adverse Events at an Incidence of at Least 5% | Aspartate aminotransferase increased | 1 participants |
| Part A: Alisertib OS | Number of Participants With Abnormal Laboratory Values Reported as Adverse Events at an Incidence of at Least 5% | Thrombocytopenia | 4 participants |
| Part A: Alisertib OS | Number of Participants With Abnormal Laboratory Values Reported as Adverse Events at an Incidence of at Least 5% | Leukopenia | 3 participants |
| Part A: Alisertib PIC | Number of Participants With Abnormal Laboratory Values Reported as Adverse Events at an Incidence of at Least 5% | Gamma-glutamyltransferase increased | 1 participants |
| Part A: Alisertib PIC | Number of Participants With Abnormal Laboratory Values Reported as Adverse Events at an Incidence of at Least 5% | Neutropenia | 8 participants |
| Part A: Alisertib PIC | Number of Participants With Abnormal Laboratory Values Reported as Adverse Events at an Incidence of at Least 5% | Leukopenia | 7 participants |
| Part A: Alisertib PIC | Number of Participants With Abnormal Laboratory Values Reported as Adverse Events at an Incidence of at Least 5% | Anaemia | 4 participants |
| Part A: Alisertib PIC | Number of Participants With Abnormal Laboratory Values Reported as Adverse Events at an Incidence of at Least 5% | Thrombocytopenia | 3 participants |
| Part A: Alisertib PIC | Number of Participants With Abnormal Laboratory Values Reported as Adverse Events at an Incidence of at Least 5% | Lymphopenia | 3 participants |
| Part A: Alisertib PIC | Number of Participants With Abnormal Laboratory Values Reported as Adverse Events at an Incidence of at Least 5% | Hypomagnesaemia | 0 participants |
| Part A: Alisertib PIC | Number of Participants With Abnormal Laboratory Values Reported as Adverse Events at an Incidence of at Least 5% | Hyperglycaemia | 1 participants |
| Part A: Alisertib PIC | Number of Participants With Abnormal Laboratory Values Reported as Adverse Events at an Incidence of at Least 5% | Hypokalaemia | 0 participants |
| Part A: Alisertib PIC | Number of Participants With Abnormal Laboratory Values Reported as Adverse Events at an Incidence of at Least 5% | White blood cell count decreased | 0 participants |
| Part A: Alisertib PIC | Number of Participants With Abnormal Laboratory Values Reported as Adverse Events at an Incidence of at Least 5% | Aspartate aminotransferase increased | 0 participants |
| Part A: Alisertib PIC | Number of Participants With Abnormal Laboratory Values Reported as Adverse Events at an Incidence of at Least 5% | Lymphocyte count decreased | 0 participants |
| Part A: Alisertib PIC | Number of Participants With Abnormal Laboratory Values Reported as Adverse Events at an Incidence of at Least 5% | Neutrophil count decreased | 1 participants |
| Part A: Alisertib PIC | Number of Participants With Abnormal Laboratory Values Reported as Adverse Events at an Incidence of at Least 5% | Hyperbilirubinaemia | 0 participants |
| Part B: OS Food Effect | Number of Participants With Abnormal Laboratory Values Reported as Adverse Events at an Incidence of at Least 5% | Gamma-glutamyltransferase increased | 0 participants |
| Part B: OS Food Effect | Number of Participants With Abnormal Laboratory Values Reported as Adverse Events at an Incidence of at Least 5% | Neutrophil count decreased | 0 participants |
| Part B: OS Food Effect | Number of Participants With Abnormal Laboratory Values Reported as Adverse Events at an Incidence of at Least 5% | Leukopenia | 2 participants |
| Part B: OS Food Effect | Number of Participants With Abnormal Laboratory Values Reported as Adverse Events at an Incidence of at Least 5% | Thrombocytopenia | 3 participants |
| Part B: OS Food Effect | Number of Participants With Abnormal Laboratory Values Reported as Adverse Events at an Incidence of at Least 5% | Lymphocyte count decreased | 0 participants |
| Part B: OS Food Effect | Number of Participants With Abnormal Laboratory Values Reported as Adverse Events at an Incidence of at Least 5% | Neutropenia | 2 participants |
| Part B: OS Food Effect | Number of Participants With Abnormal Laboratory Values Reported as Adverse Events at an Incidence of at Least 5% | Aspartate aminotransferase increased | 0 participants |
| Part B: OS Food Effect | Number of Participants With Abnormal Laboratory Values Reported as Adverse Events at an Incidence of at Least 5% | Hypokalaemia | 1 participants |
| Part B: OS Food Effect | Number of Participants With Abnormal Laboratory Values Reported as Adverse Events at an Incidence of at Least 5% | Hypomagnesaemia | 1 participants |
| Part B: OS Food Effect | Number of Participants With Abnormal Laboratory Values Reported as Adverse Events at an Incidence of at Least 5% | Anaemia | 2 participants |
| Part B: OS Food Effect | Number of Participants With Abnormal Laboratory Values Reported as Adverse Events at an Incidence of at Least 5% | Lymphopenia | 0 participants |
| Part B: OS Food Effect | Number of Participants With Abnormal Laboratory Values Reported as Adverse Events at an Incidence of at Least 5% | Hyperbilirubinaemia | 0 participants |
| Part B: OS Food Effect | Number of Participants With Abnormal Laboratory Values Reported as Adverse Events at an Incidence of at Least 5% | Hyperglycaemia | 1 participants |
| Part B: OS Food Effect | Number of Participants With Abnormal Laboratory Values Reported as Adverse Events at an Incidence of at Least 5% | White blood cell count decreased | 1 participants |
| Part C: ECT Food Effect | Number of Participants With Abnormal Laboratory Values Reported as Adverse Events at an Incidence of at Least 5% | Hyperglycaemia | 3 participants |
| Part C: ECT Food Effect | Number of Participants With Abnormal Laboratory Values Reported as Adverse Events at an Incidence of at Least 5% | Hypokalaemia | 3 participants |
| Part C: ECT Food Effect | Number of Participants With Abnormal Laboratory Values Reported as Adverse Events at an Incidence of at Least 5% | Neutrophil count decreased | 2 participants |
| Part C: ECT Food Effect | Number of Participants With Abnormal Laboratory Values Reported as Adverse Events at an Incidence of at Least 5% | White blood cell count decreased | 5 participants |
| Part C: ECT Food Effect | Number of Participants With Abnormal Laboratory Values Reported as Adverse Events at an Incidence of at Least 5% | Anaemia | 15 participants |
| Part C: ECT Food Effect | Number of Participants With Abnormal Laboratory Values Reported as Adverse Events at an Incidence of at Least 5% | Aspartate aminotransferase increased | 6 participants |
| Part C: ECT Food Effect | Number of Participants With Abnormal Laboratory Values Reported as Adverse Events at an Incidence of at Least 5% | Leukopenia | 17 participants |
| Part C: ECT Food Effect | Number of Participants With Abnormal Laboratory Values Reported as Adverse Events at an Incidence of at Least 5% | Gamma-glutamyltransferase increased | 2 participants |
| Part C: ECT Food Effect | Number of Participants With Abnormal Laboratory Values Reported as Adverse Events at an Incidence of at Least 5% | Hyperbilirubinaemia | 3 participants |
| Part C: ECT Food Effect | Number of Participants With Abnormal Laboratory Values Reported as Adverse Events at an Incidence of at Least 5% | Lymphocyte count decreased | 3 participants |
| Part C: ECT Food Effect | Number of Participants With Abnormal Laboratory Values Reported as Adverse Events at an Incidence of at Least 5% | Lymphopenia | 3 participants |
| Part C: ECT Food Effect | Number of Participants With Abnormal Laboratory Values Reported as Adverse Events at an Incidence of at Least 5% | Neutropenia | 21 participants |
| Part C: ECT Food Effect | Number of Participants With Abnormal Laboratory Values Reported as Adverse Events at an Incidence of at Least 5% | Hypomagnesaemia | 7 participants |
| Part C: ECT Food Effect | Number of Participants With Abnormal Laboratory Values Reported as Adverse Events at an Incidence of at Least 5% | Thrombocytopenia | 10 participants |
Primary
Number of Participants With Abnormal Vital Signs Reported as Adverse Events
Vital signs (blood pressure, heart rate, and oral temperature) measurements were obtained throughout the study.
Time frame: Up to 30 days after the last dose of study drug (up to 24 months approximately)
Population: Safety Population is defined as all participants who receive any amount of alisertib.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A: Alisertib OS | Number of Participants With Abnormal Vital Signs Reported as Adverse Events | Hypotension | 0 participants |
| Part A: Alisertib OS | Number of Participants With Abnormal Vital Signs Reported as Adverse Events | Sinus bradycardia | 0 participants |
| Part A: Alisertib OS | Number of Participants With Abnormal Vital Signs Reported as Adverse Events | Tachycardia | 1 participants |
| Part A: Alisertib OS | Number of Participants With Abnormal Vital Signs Reported as Adverse Events | Hypertension | 1 participants |
| Part A: Alisertib PIC | Number of Participants With Abnormal Vital Signs Reported as Adverse Events | Tachycardia | 1 participants |
| Part A: Alisertib PIC | Number of Participants With Abnormal Vital Signs Reported as Adverse Events | Sinus bradycardia | 0 participants |
| Part A: Alisertib PIC | Number of Participants With Abnormal Vital Signs Reported as Adverse Events | Hypotension | 1 participants |
| Part A: Alisertib PIC | Number of Participants With Abnormal Vital Signs Reported as Adverse Events | Hypertension | 0 participants |
| Part B: OS Food Effect | Number of Participants With Abnormal Vital Signs Reported as Adverse Events | Hypotension | 1 participants |
| Part B: OS Food Effect | Number of Participants With Abnormal Vital Signs Reported as Adverse Events | Hypertension | 1 participants |
| Part B: OS Food Effect | Number of Participants With Abnormal Vital Signs Reported as Adverse Events | Tachycardia | 1 participants |
| Part B: OS Food Effect | Number of Participants With Abnormal Vital Signs Reported as Adverse Events | Sinus bradycardia | 0 participants |
| Part C: ECT Food Effect | Number of Participants With Abnormal Vital Signs Reported as Adverse Events | Hypertension | 1 participants |
| Part C: ECT Food Effect | Number of Participants With Abnormal Vital Signs Reported as Adverse Events | Sinus bradycardia | 1 participants |
| Part C: ECT Food Effect | Number of Participants With Abnormal Vital Signs Reported as Adverse Events | Hypotension | 0 participants |
| Part C: ECT Food Effect | Number of Participants With Abnormal Vital Signs Reported as Adverse Events | Tachycardia | 0 participants |
Primary
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A Serious Adverse Event (SAE) A serious is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.
Time frame: Up to 30 days after the last dose of study drug (up to 27.4 months)
Population: Safety population was defined as all participants who receive any amount of alisertib.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A: Alisertib OS | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AE | 4 participants |
| Part A: Alisertib OS | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAE | 2 participants |
| Part A: Alisertib PIC | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAE | 4 participants |
| Part A: Alisertib PIC | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AE | 19 participants |
| Part B: OS Food Effect | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AE | 6 participants |
| Part B: OS Food Effect | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAE | 2 participants |
| Part C: ECT Food Effect | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AE | 24 participants |
| Part C: ECT Food Effect | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAE | 11 participants |
Primary
Part A: Dose-normalized AUClast (Area Under the Concentration-Time Curve From Time 0 to Time of the Last Quantifiable Concentration) for Estimation of Relative Bioavailability for Alisertib Oral Solution (OS) Versus Powder in Capsule Formulations (PIC)
Dose normalized AUClast was obtained using Cmax divided by alisertib dose in milligrams to provide values adjusted to a 1 mg alisertib dose.
Time frame: Cycles 1 and 2 Day 1 predose and at multiple time points (up to 48 hours) postdose, and, if clinically feasible, at the time of a serious or unusual AE that was judged by the investigator to be treatment related.
Population: PK evaluable population including all participants with sufficient dosing and PK data to reliably estimate PK parameters, with data available for analysis. Data for Cycle 1 and Cycle 2 were combined for analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Alisertib OS | Part A: Dose-normalized AUClast (Area Under the Concentration-Time Curve From Time 0 to Time of the Last Quantifiable Concentration) for Estimation of Relative Bioavailability for Alisertib Oral Solution (OS) Versus Powder in Capsule Formulations (PIC) | 530.18 nM*hr/mg | Standard Deviation 177.75 |
| Part A: Alisertib PIC | Part A: Dose-normalized AUClast (Area Under the Concentration-Time Curve From Time 0 to Time of the Last Quantifiable Concentration) for Estimation of Relative Bioavailability for Alisertib Oral Solution (OS) Versus Powder in Capsule Formulations (PIC) | 372.53 nM*hr/mg | Standard Deviation 145.19 |
90% CI: [1.08, 1.78]
Primary
Part A: Dose-normalized Cmax (Maximum Observed Concentration) for Estimation of Relative Bioavailability for Alisertib Oral Solution (OS) Versus Powder in Capsule Formulations (PIC)
Dose normalized Cmax was obtained using Cmax divided by alisertib dose in milligrams to provide values adjusted to a 1 mg alisertib dose.
Time frame: Cycles 1 and 2 Day 1 predose and at multiple time points (up to 48 hours) postdose, and, if clinically feasible, at the time of a serious or unusual adverse event (AE) that was judged by the investigator to be treatment related.
Population: Pharmacokinetic (PK)-evaluable population including all participants with sufficient dosing and PK data to reliably estimate PK parameters, with data available for analysis. Data for Cycle 1 and Cycle 2 were combined for analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Alisertib OS | Part A: Dose-normalized Cmax (Maximum Observed Concentration) for Estimation of Relative Bioavailability for Alisertib Oral Solution (OS) Versus Powder in Capsule Formulations (PIC) | 58.78 nM/mg | Standard Deviation 22.583 |
| Part A: Alisertib PIC | Part A: Dose-normalized Cmax (Maximum Observed Concentration) for Estimation of Relative Bioavailability for Alisertib Oral Solution (OS) Versus Powder in Capsule Formulations (PIC) | 31.40 nM/mg | Standard Deviation 11.404 |
90% CI: [1.52, 2.37]
Primary
Part B: AUClast: Area Under the Concentration-Time Curve From Time 0 to Time of the Last Quantifiable Concentration for Alisertib Administered as an Oral Solution With Food Versus Without Food
Not performed.
Time frame: Cycles 1 and 2 Day 1 predose and at multiple time points (up to 48 hours) postdose, and, if clinically feasible, at the time of a serious or unusual AE that was judged by the investigator to be treatment related.
Population: Data from Part B were not analyzed as planned because this part of the study was terminated after only 6 of the planned 14 PK-evaluable participants were enrolled, as the OS was not stable and gelled prior to dosing. With PK evaluability being compromised by gelling of the OS, the data were not analyzed as planned.
Primary
Part B: AUCτ: Area Under the Concentration-Time Curve From Time 0 to End of Dosing Interval for Alisertib Oral Solution Following Multiple-Dose Administration
Not performed.
Time frame: Cycle 1 Day 9 predose and at multiple time points (up to 12 hours) postdose, and, if clinically feasible, at the time of a serious or unusual AE that was judged by the investigator to be treatment related.
Population: Data from Part B were not analyzed as planned because this part of the study was terminated after only 6 of the planned 14 PK-evaluable participants were enrolled, as the OS was not stable and gelled prior to dosing. With PK evaluability being compromised by gelling of the OS, the data were not analyzed as planned.
Primary
Part B: Cmax: Maximum Observed Concentration for Alisertib Administered as an Oral Solution With Food Versus Without Food
Not performed.
Time frame: Cycles 1 and 2 Day 1 predose and at multiple time points (up to 48 hours) postdose, and, if clinically feasible, at the time of a serious or unusual AE that was judged by the investigator to be treatment related.
Population: Data from Part B were not analyzed as planned because this part of the study was terminated after only 6 of the planned 14 PK-evaluable participants were enrolled, as the OS was not stable and gelled prior to dosing. With PK evaluability being compromised by gelling of the OS, the data were not analyzed as planned.
Primary
Part B: Cmax: Maximum Plasma Concentration for Alisertib Oral Solution Following Multiple-Dose Administration
Not performed.
Time frame: Cycle 1 Day 9 predose and at multiple time points (up to 12 hours) postdose, and, if clinically feasible, at the time of a serious or unusual AE that was judged by the investigator to be treatment related.
Population: Data from Part B were not analyzed as planned because this part of the study was terminated after only 6 of the planned 14 PK-evaluable participants were enrolled, as the OS was not stable and gelled prior to dosing. With PK evaluability being compromised by gelling of the OS, the data were not analyzed as planned.
Primary
Part B: Tmax: Time of First Occurrence of Cmax Over the Dosing Interval for Alisertib Oral Solution Following Multiple-Dose Administration
Not performed.
Time frame: Cycle 1 Day 9 predose and at multiple time points (up to 12 hours) postdose, and, if clinically feasible, at the time of a serious or unusual AE that was judged by the investigator to be treatment related.
Population: Data from Part B were not analyzed as planned because this part of the study was terminated after only 6 of the planned 14 PK-evaluable participants were enrolled, as the OS was not stable and gelled prior to dosing. With PK evaluability being compromised by gelling of the OS, the data were not analyzed as planned.
Primary
Part C: AUC∞: Area Under the Concentration-Time Curve From Time 0 to Infinity, Calculated Using the Observed Value of the Last Quantifiable Concentration for Alisertib Administered as an Enteric-Coated Capsule (ECT) With Food Versus Without Food
Time frame: Cycles 1 and 2 on Day 1 predose and at multiple time points (up to 48 hours) postdose, and, if clinically feasible, at the time of a serious or unusual AE that was judged by the investigator to be treatment related.
Population: The PK evaluable population including all participants with sufficient dosing and PK data to reliably estimate PK parameters, with data available for analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Alisertib OS | Part C: AUC∞: Area Under the Concentration-Time Curve From Time 0 to Infinity, Calculated Using the Observed Value of the Last Quantifiable Concentration for Alisertib Administered as an Enteric-Coated Capsule (ECT) With Food Versus Without Food | 30627.3 nM*h | Standard Error 21000.29 |
| Part A: Alisertib PIC | Part C: AUC∞: Area Under the Concentration-Time Curve From Time 0 to Infinity, Calculated Using the Observed Value of the Last Quantifiable Concentration for Alisertib Administered as an Enteric-Coated Capsule (ECT) With Food Versus Without Food | 28507.1 nM*h | Standard Error 15637.5 |
90% CI: [0.68, 1.32]
Primary
Part C: AUClast: Area Under the Concentration-Time Curve From Time 0 to Time of the Last Quantifiable Concentration for Alisertib Administered as an Enteric-Coated Capsule (ECT) With Food Versus Without Food
Time frame: Cycles 1 and 2 on Day 1 predose and at multiple time points (up to 48 hours) postdose, and, if clinically feasible, at the time of a serious or unusual AE that was judged by the investigator to be treatment related.
Population: The PK evaluable population including all participants with sufficient dosing and PK data to reliably estimate PK parameters, with data available for analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Alisertib OS | Part C: AUClast: Area Under the Concentration-Time Curve From Time 0 to Time of the Last Quantifiable Concentration for Alisertib Administered as an Enteric-Coated Capsule (ECT) With Food Versus Without Food | 23928.6 nM*h | Standard Deviation 14343.56 |
| Part A: Alisertib PIC | Part C: AUClast: Area Under the Concentration-Time Curve From Time 0 to Time of the Last Quantifiable Concentration for Alisertib Administered as an Enteric-Coated Capsule (ECT) With Food Versus Without Food | 24135.0 nM*h | Standard Deviation 11757.15 |
90% CI: [0.8, 1.34]
Primary
Part C: Cmax: Maximum Observed Concentration for Alisertib Administered as an Enteric-Coated Capsule (ECT) With Food Versus Without Food
Participants were randomized to receive 50-mg alisertib as an ECT (single, 50-mg strength tablets) under fasted or fed (following a standardized high-fat meal) conditions.
Time frame: Cycles 1 and 2 Day 1 predose and at multiple time points (up to 48 hours) postdose, and, if clinically feasible, at the time of a serious or unusual AE that was judged by the investigator to be treatment related.
Population: PK-evaluable population including all participants with sufficient dosing and PK data to reliably estimate PK parameters, with data available for analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Alisertib OS | Part C: Cmax: Maximum Observed Concentration for Alisertib Administered as an Enteric-Coated Capsule (ECT) With Food Versus Without Food | 1757.9 nM | Standard Deviation 924.5 |
| Part A: Alisertib PIC | Part C: Cmax: Maximum Observed Concentration for Alisertib Administered as an Enteric-Coated Capsule (ECT) With Food Versus Without Food | 1401.2 nM | Standard Deviation 501 |
90% CI: [0.66, 1.06]
Secondary
Best Overall Response (CR+PR) Based on Investigator's Assessment According to the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Best overall response is defined as the number of participants with Complete Response (CR) + Partial Response (PR) as assessed by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.1 for target lesions and assessed by CT or MRI. CR is defined as disappearance of all target lesions and PR is defined as 30% decrease in the sum of the longest diameter (LD) of target lesions. Stable Disease (SD) is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Progressive Disease, taking as reference the smallest sum LD since the treatment started.
Time frame: At the completion of Cycle 2 and every 2 cycles (every 6 weeks) until Cycle 6 (18 weeks). After Cycle 6 (18 weeks), CT/MRI scans (with contrast) were to be performed every 3 cycles (9 weeks) until PD was documented.
Population: Efficacy analysis included all participants who had a baseline response assessment and at least one on-study response assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A: Alisertib OS | Best Overall Response (CR+PR) Based on Investigator's Assessment According to the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | Best Overall Response of CR or PR | 0 participants |
| Part A: Alisertib OS | Best Overall Response (CR+PR) Based on Investigator's Assessment According to the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | Best Overall Response of Stable Disease | 0 participants |
| Part A: Alisertib PIC | Best Overall Response (CR+PR) Based on Investigator's Assessment According to the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | Best Overall Response of CR or PR | 0 participants |
| Part A: Alisertib PIC | Best Overall Response (CR+PR) Based on Investigator's Assessment According to the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | Best Overall Response of Stable Disease | 1 participants |
| Part B: OS Food Effect | Best Overall Response (CR+PR) Based on Investigator's Assessment According to the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | Best Overall Response of CR or PR | 0 participants |
| Part B: OS Food Effect | Best Overall Response (CR+PR) Based on Investigator's Assessment According to the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | Best Overall Response of Stable Disease | 5 participants |
| Part C: ECT Food Effect | Best Overall Response (CR+PR) Based on Investigator's Assessment According to the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | Best Overall Response of CR or PR | 0 participants |
| Part C: ECT Food Effect | Best Overall Response (CR+PR) Based on Investigator's Assessment According to the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | Best Overall Response of Stable Disease | 2 participants |
| Part B: OS Food Effect Fasted/Fed (Sequence B) | Best Overall Response (CR+PR) Based on Investigator's Assessment According to the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | Best Overall Response of CR or PR | 0 participants |
| Part B: OS Food Effect Fasted/Fed (Sequence B) | Best Overall Response (CR+PR) Based on Investigator's Assessment According to the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | Best Overall Response of Stable Disease | 1 participants |
| Part C: ECT Food Effect Fed/Fasted (Sequence A) | Best Overall Response (CR+PR) Based on Investigator's Assessment According to the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | Best Overall Response of CR or PR | 0 participants |
| Part C: ECT Food Effect Fed/Fasted (Sequence A) | Best Overall Response (CR+PR) Based on Investigator's Assessment According to the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | Best Overall Response of Stable Disease | 6 participants |
| Part C: ECT Food Effect Fasted/Fed (Sequence B) | Best Overall Response (CR+PR) Based on Investigator's Assessment According to the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | Best Overall Response of CR or PR | 0 participants |
| Part C: ECT Food Effect Fasted/Fed (Sequence B) | Best Overall Response (CR+PR) Based on Investigator's Assessment According to the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 | Best Overall Response of Stable Disease | 6 participants |