Trial Outcomes & Findings for Study of MLN8237 in Participants With Advanced Hematological Malignancies (NCT NCT00697346)

Last Updated: 2019-05-31

Results Overview

DLT was evaluated according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.0 and was defined as any of the following events related to therapy with alisertib:1. Grade 4 neutropenia lasting ≥7 consecutive days, 2. Grade 4 neutropenia with fever and/or infection 3. Platelet count \<25,000/mm\^3 4. Grade 3 or greater nausea and/or emesis despite use of optimal antiemetic prophylaxis 5. Grade 3 or greater diarrhea despite maximal supportive therapy with loperamide 6. Any other Grade 3 or greater nonhematologic toxicity, with the following exceptions: Grade 3 arthralgia/myalgias, Any grade of alopecia, Brief (\<1 week) Grade 3 fatigue 7. Treatment delay of \>21 days due to failure of adequate hematologic or non-hematologic recovery from previous cycle of treatment 8. Other alisertib related non-hematologic toxicities ≥Grade 2 that, in the opinion of the investigator required a dose reduction or discontinuation of therapy with alisertib.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

58 participants

Primary outcome timeframe

From first dose of study drug to 30 days after the last dose (up to 422 days)

Results posted on

2019-05-31

Participant Flow

Participants took part in the study at 10 investigative sites in the United States from 11 July 2008 to19 October 2016.

Participants with a diagnosis of advanced hematological malignancies were enrolled 1 of 3 treatment groups, Part 1:alisertib powder-in capsule (PIC) 25 to 90 mg dose escalation cohort, Part 1: alisertib 30 to 50 mg enteric-coated tablet (ECT) dose escalation cohort, or Part 2: alisertib ECT 50 mg participants with peripheral T-cell lymphoma (PTCL).

Participant milestones

Participant milestones
Measure	Part 1: PIC Dose Escalation Alisertib 25 or 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days followed by a 7-day recovery period in 28-day cycles or alisertib 35, 45, 65 or 90 mg PIC, orally, QD for 14 days followed by a 14-day recovery period in 28-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 14 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose), followed by their respective dosage assignment.	Part 1: ECT Dose Escalation Alisertib 40 mg, Enteric-coated Tablet (ECT) formulation, orally, QD for 14 days followed by a 14-day recovery period in 28-day cycles, or alisertib 30, 40 or 50 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles).	Part 2: PTCL Participants with peripheral T-cell lymphoma (PTCL) received alisertib 50 mg ECT, orally, BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
Overall Study STARTED	28	28	2
Overall Study COMPLETED	0	2	1
Overall Study NOT COMPLETED	28	26	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Part 1: PIC Dose Escalation Alisertib 25 or 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days followed by a 7-day recovery period in 28-day cycles or alisertib 35, 45, 65 or 90 mg PIC, orally, QD for 14 days followed by a 14-day recovery period in 28-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 14 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose), followed by their respective dosage assignment.	Part 1: ECT Dose Escalation Alisertib 40 mg, Enteric-coated Tablet (ECT) formulation, orally, QD for 14 days followed by a 14-day recovery period in 28-day cycles, or alisertib 30, 40 or 50 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles).	Part 2: PTCL Participants with peripheral T-cell lymphoma (PTCL) received alisertib 50 mg ECT, orally, BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).
Overall Study Adverse Event	4	5	0
Overall Study Progressive Disease	19	18	0
Overall Study Symptomatic Deterioration	0	1	0
Overall Study Withdrawal by Subject	2	2	0
Overall Study Reason not Specified	3	0	1

Baseline Characteristics

Here number analyzed is the number of participants who were evaluated for height at baseline.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part 1: PIC Dose Escalation n=28 Participants Alisertib 25 or 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days followed by a 7-day recovery period in 28-day cycles or alisertib 35, 45, 65 or 90 mg PIC, orally, QD for 14 days followed by a 14-day recovery period in 28-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 14 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose), followed by their respective dosage assignment.	Part 1: ECT Dose Escalation n=28 Participants Alisertib 40 mg, Enteric-coated Tablet (ECT) formulation, orally, QD for 14 days followed by a 14-day recovery period in 28-day cycles, or alisertib 30, 40 or 50 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles).	Part 2: PTCL n=2 Participants Participants with peripheral T-cell lymphoma (PTCL) received alisertib 50 mg ECT, orally, BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles).	Total n=58 Participants Total of all reporting groups
Age, Continuous	61.4 years STANDARD_DEVIATION 8.91 • n=28 Participants	59.5 years STANDARD_DEVIATION 14.22 • n=28 Participants	63.0 years STANDARD_DEVIATION 24.04 • n=2 Participants	60.5 years STANDARD_DEVIATION 12.03 • n=58 Participants
Sex: Female, Male Female	14 Participants n=28 Participants	15 Participants n=28 Participants	2 Participants n=2 Participants	31 Participants n=58 Participants
Sex: Female, Male Male	14 Participants n=28 Participants	13 Participants n=28 Participants	0 Participants n=2 Participants	27 Participants n=58 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	9 Participants n=28 Participants	7 Participants n=28 Participants	0 Participants n=2 Participants	16 Participants n=58 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	19 Participants n=28 Participants	20 Participants n=28 Participants	2 Participants n=2 Participants	41 Participants n=58 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=28 Participants	1 Participants n=28 Participants	0 Participants n=2 Participants	1 Participants n=58 Participants
Race/Ethnicity, Customized White	24 participants n=28 Participants	26 participants n=28 Participants	2 participants n=2 Participants	52 participants n=58 Participants
Race/Ethnicity, Customized Black or African American	3 participants n=28 Participants	1 participants n=28 Participants	0 participants n=2 Participants	4 participants n=58 Participants
Race/Ethnicity, Customized Asian	0 participants n=28 Participants	1 participants n=28 Participants	0 participants n=2 Participants	1 participants n=58 Participants
Race/Ethnicity, Customized Not Reported	1 participants n=28 Participants	0 participants n=28 Participants	0 participants n=2 Participants	1 participants n=58 Participants
Region of Enrollment United States	28 participants n=28 Participants	28 participants n=28 Participants	2 participants n=2 Participants	58 participants n=58 Participants
Height	165.9 cm STANDARD_DEVIATION 11.25 • n=28 Participants • Here number analyzed is the number of participants who were evaluated for height at baseline.	164.6 cm STANDARD_DEVIATION 10.95 • n=26 Participants • Here number analyzed is the number of participants who were evaluated for height at baseline.	160.6 cm STANDARD_DEVIATION 6.43 • n=2 Participants • Here number analyzed is the number of participants who were evaluated for height at baseline.	165.1 cm STANDARD_DEVIATION 10.89 • n=56 Participants • Here number analyzed is the number of participants who were evaluated for height at baseline.
Weight	81.40 kg STANDARD_DEVIATION 20.031 • n=28 Participants	77.62 kg STANDARD_DEVIATION 19.747 • n=28 Participants	97.65 kg STANDARD_DEVIATION 43.911 • n=2 Participants	80.13 kg STANDARD_DEVIATION 20.573 • n=58 Participants
Body Surface Area	1.93 m^2 STANDARD_DEVIATION 0.282 • n=28 Participants • Here number analyzed is the number of participants who were evaluated for body surface area at baseline.	1.88 m^2 STANDARD_DEVIATION 0.289 • n=26 Participants • Here number analyzed is the number of participants who were evaluated for body surface area at baseline.	2.05 m^2 STANDARD_DEVIATION 0.434 • n=2 Participants • Here number analyzed is the number of participants who were evaluated for body surface area at baseline.	1.91 m^2 STANDARD_DEVIATION 0.286 • n=56 Participants • Here number analyzed is the number of participants who were evaluated for body surface area at baseline.

PRIMARY outcome

Timeframe: From first dose of study drug to 30 days after the last dose (up to 422 days)

Population: DLT evaluable population included all participants who received at least 75% of their planned alisertib doses for their first cycle of treatment (unless interrupted by DLT) and had sufficient follow up data to allow the investigators and sponsor to determine whether DLT occurred.

Outcome measures

Outcome measures
Measure	Alisertib 25mg PIC QD 21D n=6 Participants Alisertib 25 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days (D) followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 21D n=4 Participants Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 14D n=3 Participants Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 45 mg PIC QD 14D n=6 Participants Alisertib 45 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity to (up 4 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 65 mg PIC QD 14D n=6 Participants Alisertib 65 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 90 mg PIC QD 14D n=2 Participants Alisertib 90 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT QD 14D n=4 Participants Alisertib 40 mg, Enteric-coated Tablet (ECT) formulation, orally, QD for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 30 mg ECT BID 7D n=3 Participants Alisertib 30 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT BID 7D n=7 Participants alisertib 40 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 50 mg ECT BID 7D n=9 Participants Alisertib 50 mg ECT, orally BID for 7 Ddays followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).
Number of Participants With Dose-Limiting Toxicity (DLT)	1 participants	2 participants	0 participants	1 participants	2 participants	2 participants	2 participants	0 participants	0 participants	1 participants

PRIMARY outcome

Timeframe: From first dose of study drug to 30 days after the last dose (up to 422 days)

MTD was defined as the highest dose at which DLT occurred in 0/3 or 1/6 participants.

Outcome measures

Outcome measures
Measure	Alisertib 25mg PIC QD 21D n=58 Participants Alisertib 25 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days (D) followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 21D Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 14D Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 45 mg PIC QD 14D Alisertib 45 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity to (up 4 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 65 mg PIC QD 14D Alisertib 65 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 90 mg PIC QD 14D Alisertib 90 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT QD 14D Alisertib 40 mg, Enteric-coated Tablet (ECT) formulation, orally, QD for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 30 mg ECT BID 7D Alisertib 30 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT BID 7D alisertib 40 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 50 mg ECT BID 7D Alisertib 50 mg ECT, orally BID for 7 Ddays followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).
Maximum Tolerated Dose (MTD) of Alisertib	50 mg BID for 7 days	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Cycle 1 Day 1 predose and at multiple timepoints (up to 24 hours) postdose

Population: Pharmacokinetic (PK) evaluable population included all participants for whom there were sufficient dosing and alisertib concentration time data to permit non-compartmental PK analysis.

Outcome measures

Outcome measures
Measure	Alisertib 25mg PIC QD 21D n=6 Participants Alisertib 25 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days (D) followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 21D n=4 Participants Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 14D Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 45 mg PIC QD 14D Alisertib 45 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity to (up 4 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 65 mg PIC QD 14D Alisertib 65 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 90 mg PIC QD 14D Alisertib 90 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT QD 14D Alisertib 40 mg, Enteric-coated Tablet (ECT) formulation, orally, QD for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 30 mg ECT BID 7D Alisertib 30 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT BID 7D alisertib 40 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 50 mg ECT BID 7D Alisertib 50 mg ECT, orally BID for 7 Ddays followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).
Cmax: Maximum Observed Concentration for Alisertib as Pill in Capsule (PIC) With Once Daily for 21 Days (QD21D) Dosing at Day 1	833.2 nM Geometric Coefficient of Variation 49.5	1078.3 nM Geometric Coefficient of Variation 26.4	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Cycle 1 Day 21 predose and at multiple timepoints (up to 6 hours) postdose

Population: PK evaluable population included all participants for whom there were sufficient dosing and alisertib concentration time data to permit non-compartmental PK analysis. Here number of participants analyzed were participants evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure	Alisertib 25mg PIC QD 21D n=6 Participants Alisertib 25 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days (D) followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 21D n=3 Participants Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 14D Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 45 mg PIC QD 14D Alisertib 45 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity to (up 4 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 65 mg PIC QD 14D Alisertib 65 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 90 mg PIC QD 14D Alisertib 90 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT QD 14D Alisertib 40 mg, Enteric-coated Tablet (ECT) formulation, orally, QD for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 30 mg ECT BID 7D Alisertib 30 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT BID 7D alisertib 40 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 50 mg ECT BID 7D Alisertib 50 mg ECT, orally BID for 7 Ddays followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).
Cmax: Maximum Observed Concentration for Alisertib as Pill in Capsule (PIC) With Once Daily for 21 Days (QD21D) Dosing at Day 21	1337.6 nM Geometric Coefficient of Variation 57.8	1451.9 nM Geometric Coefficient of Variation 26.2	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Cycle 1 Day 1 predose and at multiple timepoints (up to 24 hours) postdose

Outcome measures

Outcome measures
Measure	Alisertib 25mg PIC QD 21D n=6 Participants Alisertib 25 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days (D) followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 21D n=4 Participants Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 14D Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 45 mg PIC QD 14D Alisertib 45 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity to (up 4 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 65 mg PIC QD 14D Alisertib 65 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 90 mg PIC QD 14D Alisertib 90 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT QD 14D Alisertib 40 mg, Enteric-coated Tablet (ECT) formulation, orally, QD for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 30 mg ECT BID 7D Alisertib 30 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT BID 7D alisertib 40 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 50 mg ECT BID 7D Alisertib 50 mg ECT, orally BID for 7 Ddays followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).
Tmax: Time of First Occurrence of Cmax for Alisertib as Pill in Capsule (PIC) With Once Daily for 21 Days (QD21D) Dosing at Day 1	2.0 hours (h) Interval 2.0 to 3.3	2.0 hours (h) Interval 1.1 to 5.2	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Cycle 1 Day 21 predose and at multiple timepoints (up to 6 hours) postdose

Outcome measures

Outcome measures
Measure	Alisertib 25mg PIC QD 21D n=6 Participants Alisertib 25 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days (D) followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 21D n=3 Participants Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 14D Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 45 mg PIC QD 14D Alisertib 45 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity to (up 4 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 65 mg PIC QD 14D Alisertib 65 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 90 mg PIC QD 14D Alisertib 90 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT QD 14D Alisertib 40 mg, Enteric-coated Tablet (ECT) formulation, orally, QD for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 30 mg ECT BID 7D Alisertib 30 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT BID 7D alisertib 40 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 50 mg ECT BID 7D Alisertib 50 mg ECT, orally BID for 7 Ddays followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).
Tmax: Time of First Occurrence of Cmax for Alisertib as Pill in Capsule (PIC) With Once Daily for 21 Days (QD21D) Dosing at Day 21	2.0 h Interval 1.0 to 5.0	2.0 h Interval 2.0 to 2.0	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Cycle 1 Day 21 predose and at multiple time points (up to 6 hours) postdose

Outcome measures

Outcome measures
Measure	Alisertib 25mg PIC QD 21D n=6 Participants Alisertib 25 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days (D) followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 21D n=3 Participants Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 14D Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 45 mg PIC QD 14D Alisertib 45 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity to (up 4 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 65 mg PIC QD 14D Alisertib 65 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 90 mg PIC QD 14D Alisertib 90 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT QD 14D Alisertib 40 mg, Enteric-coated Tablet (ECT) formulation, orally, QD for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 30 mg ECT BID 7D Alisertib 30 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT BID 7D alisertib 40 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 50 mg ECT BID 7D Alisertib 50 mg ECT, orally BID for 7 Ddays followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).
AUCt: Area Under the Concentration Time Curve From Time 0 to Time t for Alisertib as Pill in Capsule (PIC) With Once Daily for 21 Days (QD21D) Dosing at Day 21	14846 nM*h Geometric Coefficient of Variation 69.7	16528 nM*h Geometric Coefficient of Variation 35.6	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Cycle 1 Day 21 predose and at multiple time points (up to 6 hours) postdose

Outcome measures

Outcome measures
Measure	Alisertib 25mg PIC QD 21D n=5 Participants Alisertib 25 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days (D) followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 21D n=3 Participants Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 14D Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 45 mg PIC QD 14D Alisertib 45 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity to (up 4 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 65 mg PIC QD 14D Alisertib 65 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 90 mg PIC QD 14D Alisertib 90 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT QD 14D Alisertib 40 mg, Enteric-coated Tablet (ECT) formulation, orally, QD for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 30 mg ECT BID 7D Alisertib 30 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT BID 7D alisertib 40 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 50 mg ECT BID 7D Alisertib 50 mg ECT, orally BID for 7 Ddays followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).
Terminal Half-Life (t1/2) for Alisertib as Pill in Capsule (PIC) With Once Daily for 21 Days (QD21D) Dosing at Day 21	20.5 h Standard Deviation 7.3	19.5 h Standard Deviation 6.0	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Cycle 1 Day 21 predose and at multiple time points (up to 6 hours) postdose

Outcome measures

Outcome measures
Measure	Alisertib 25mg PIC QD 21D n=6 Participants Alisertib 25 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days (D) followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 21D n=3 Participants Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 14D Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 45 mg PIC QD 14D Alisertib 45 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity to (up 4 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 65 mg PIC QD 14D Alisertib 65 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 90 mg PIC QD 14D Alisertib 90 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT QD 14D Alisertib 40 mg, Enteric-coated Tablet (ECT) formulation, orally, QD for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 30 mg ECT BID 7D Alisertib 30 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT BID 7D alisertib 40 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 50 mg ECT BID 7D Alisertib 50 mg ECT, orally BID for 7 Ddays followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).
Accumulation Ratio (Rac) for Alisertib as Pill in Capsule (PIC) With Once Daily for 21 Days (QD21D) Dosing at Day 21	1.9 ratio Standard Deviation 1.1	1.5 ratio Standard Deviation 0.5	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Cycle 1 Day 21 predose and at multiple timepoints (up to 6 hours) postdose

Population: PK evaluable population included all participants for whom there were sufficient dosing and alisertib concentration time data to permit non-compartmental PK analysis, with data available at the given time point. Here number of participants analyzed were participants evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure	Alisertib 25mg PIC QD 21D n=6 Participants Alisertib 25 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days (D) followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 21D n=3 Participants Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 14D Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 45 mg PIC QD 14D Alisertib 45 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity to (up 4 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 65 mg PIC QD 14D Alisertib 65 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 90 mg PIC QD 14D Alisertib 90 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT QD 14D Alisertib 40 mg, Enteric-coated Tablet (ECT) formulation, orally, QD for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 30 mg ECT BID 7D Alisertib 30 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT BID 7D alisertib 40 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 50 mg ECT BID 7D Alisertib 50 mg ECT, orally BID for 7 Ddays followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).
Peak/Trough Ratio for Alisertib as Pill in Capsule (PIC) With Once Daily for 21 Days (QD21D) Dosing at Day 21	6.0 ratio Standard Deviation 4.4	4.3 ratio Standard Deviation 1.5	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Cycle 1 Day 21 predose and at multiple timepoints (up to 6 hours) postdose

Population: PK evaluable population included all participants for whom there were sufficient dosing and alisertib concentration time data to permit non-compartmental PK analysis, with data available at the given time point. Here number of participants analyzed were participants evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure	Alisertib 25mg PIC QD 21D n=6 Participants Alisertib 25 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days (D) followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 21D n=3 Participants Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 14D Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 45 mg PIC QD 14D Alisertib 45 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity to (up 4 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 65 mg PIC QD 14D Alisertib 65 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 90 mg PIC QD 14D Alisertib 90 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT QD 14D Alisertib 40 mg, Enteric-coated Tablet (ECT) formulation, orally, QD for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 30 mg ECT BID 7D Alisertib 30 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT BID 7D alisertib 40 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 50 mg ECT BID 7D Alisertib 50 mg ECT, orally BID for 7 Ddays followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).
CLss/F: Apparent Oral Clearance at Steady State for Alisertib as Pill in Capsule (PIC) With Once Daily for 21 Days (QD21D) Dosing at Day 21	3.2 L/h Geometric Coefficient of Variation 113	4.1 L/h Geometric Coefficient of Variation 45	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Cycle 1 Day 1 predose and at multiple timepoints (up to 24 hours) postdose

Population: PK evaluable population included all participants for whom there were sufficient dosing and alisertib concentration time data to permit non-compartmental PK analysis.

Outcome measures

Outcome measures
Measure	Alisertib 25mg PIC QD 21D n=3 Participants Alisertib 25 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days (D) followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 21D n=6 Participants Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 14D n=7 Participants Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 45 mg PIC QD 14D n=2 Participants Alisertib 45 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity to (up 4 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 65 mg PIC QD 14D Alisertib 65 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 90 mg PIC QD 14D Alisertib 90 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT QD 14D Alisertib 40 mg, Enteric-coated Tablet (ECT) formulation, orally, QD for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 30 mg ECT BID 7D Alisertib 30 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT BID 7D alisertib 40 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 50 mg ECT BID 7D Alisertib 50 mg ECT, orally BID for 7 Ddays followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).
Cmax: Maximum Observed Concentration for Alisertib as Pill in Capsule (PIC) With Once Daily for 14 Days (QD14D) Dosing at Day 1	726.5 nM Geometric Coefficient of Variation 34.8	1637.0 nM Geometric Coefficient of Variation 58.0	1773.4 nM Geometric Coefficient of Variation 44.3	2497.4 nM Geometric Coefficient of Variation 24.3	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Cycle 1 Day 14 predose and at multiple timepoints (up to 8 hours) postdose

Outcome measures

Outcome measures
Measure	Alisertib 25mg PIC QD 21D n=2 Participants Alisertib 25 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days (D) followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 21D n=5 Participants Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 14D n=6 Participants Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 45 mg PIC QD 14D Alisertib 45 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity to (up 4 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 65 mg PIC QD 14D Alisertib 65 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 90 mg PIC QD 14D Alisertib 90 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT QD 14D Alisertib 40 mg, Enteric-coated Tablet (ECT) formulation, orally, QD for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 30 mg ECT BID 7D Alisertib 30 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT BID 7D alisertib 40 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 50 mg ECT BID 7D Alisertib 50 mg ECT, orally BID for 7 Ddays followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).
Cmax: Maximum Observed Concentration for Alisertib as Pill in Capsule (PIC) With Once Daily for 14 Days (QD14D) Dosing at Day 14	2193.5 nM Geometric Coefficient of Variation NA Geometric Coefficient of Variation was not calculated for 2 participants.	1634.4 nM Geometric Coefficient of Variation 52.5	2300.2 nM Geometric Coefficient of Variation 40.3	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Cycle 1 Day 1 predose and at multiple timepoints (up to 24 hours) postdose

Population: PK evaluable population included all participants for whom there were sufficient dosing and alisertib concentration time data to permit non-compartmental PK analysis.

Outcome measures

Outcome measures
Measure	Alisertib 25mg PIC QD 21D n=3 Participants Alisertib 25 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days (D) followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 21D n=6 Participants Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 14D n=7 Participants Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 45 mg PIC QD 14D n=2 Participants Alisertib 45 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity to (up 4 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 65 mg PIC QD 14D Alisertib 65 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 90 mg PIC QD 14D Alisertib 90 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT QD 14D Alisertib 40 mg, Enteric-coated Tablet (ECT) formulation, orally, QD for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 30 mg ECT BID 7D Alisertib 30 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT BID 7D alisertib 40 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 50 mg ECT BID 7D Alisertib 50 mg ECT, orally BID for 7 Ddays followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).
Tmax: Time of First Occurrence of Cmax for Alisertib as Pill in Capsule (PIC) With Once Daily for 14 Days (QD14D) Dosing at Day 1	2.0 h Full Range 34.8 • Interval 1.9 to 4.0	3.0 h Full Range 58.0 • Interval 1.1 to 4.0	2.0 h Full Range 44.3 • Interval 1.9 to 6.0	2.9 h Full Range 24.3 • Interval 1.5 to 4.3	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Cycle 1 Day 14 predose and at multiple timepoints (up to 8 hours) postdose

Outcome measures

Outcome measures
Measure	Alisertib 25mg PIC QD 21D n=2 Participants Alisertib 25 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days (D) followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 21D n=5 Participants Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 14D n=6 Participants Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 45 mg PIC QD 14D Alisertib 45 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity to (up 4 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 65 mg PIC QD 14D Alisertib 65 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 90 mg PIC QD 14D Alisertib 90 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT QD 14D Alisertib 40 mg, Enteric-coated Tablet (ECT) formulation, orally, QD for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 30 mg ECT BID 7D Alisertib 30 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT BID 7D alisertib 40 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 50 mg ECT BID 7D Alisertib 50 mg ECT, orally BID for 7 Ddays followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).
Tmax: Time of First Occurrence of Cmax for Alisertib as Pill in Capsule (PIC) With Once Daily for 14 Days (QD14D) Dosing at Day 14	3.4 h Full Range NA • Interval 0.8 to 6.1	2.0 h Full Range 52.5 • Interval 2.0 to 4.0	2.0 h Full Range 40.3 • Interval 1.5 to 2.1	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Cycle 1 Day 14 predose and at multiple timepoints (up to 8 hours) postdose

Outcome measures

Outcome measures
Measure	Alisertib 25mg PIC QD 21D n=2 Participants Alisertib 25 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days (D) followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 21D n=5 Participants Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 14D n=6 Participants Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 45 mg PIC QD 14D Alisertib 45 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity to (up 4 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 65 mg PIC QD 14D Alisertib 65 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 90 mg PIC QD 14D Alisertib 90 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT QD 14D Alisertib 40 mg, Enteric-coated Tablet (ECT) formulation, orally, QD for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 30 mg ECT BID 7D Alisertib 30 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT BID 7D alisertib 40 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 50 mg ECT BID 7D Alisertib 50 mg ECT, orally BID for 7 Ddays followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).
AUCt: Area Under the Concentration Time Curve From Time 0 to Time t for Alisertib as Pill in Capsule (PIC) With Once Daily for 14 Days (QD14D) Dosing at Day 14	23444 nM*h Geometric Coefficient of Variation NA • Interval 1.9 to 4.0 Geometric Coefficient of Variation was not calculated for 2 participants.	19671 nM*h Geometric Coefficient of Variation 64.8 • Interval 1.1 to 4.0	28864 nM*h Geometric Coefficient of Variation 39.9 • Interval 1.9 to 6.0	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Cycle 1 Day 14 predose and at multiple timepoints (up to 8 hours) postdose

Outcome measures

Outcome measures
Measure	Alisertib 25mg PIC QD 21D n=2 Participants Alisertib 25 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days (D) followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 21D n=5 Participants Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 14D n=6 Participants Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 45 mg PIC QD 14D Alisertib 45 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity to (up 4 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 65 mg PIC QD 14D Alisertib 65 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 90 mg PIC QD 14D Alisertib 90 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT QD 14D Alisertib 40 mg, Enteric-coated Tablet (ECT) formulation, orally, QD for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 30 mg ECT BID 7D Alisertib 30 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT BID 7D alisertib 40 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 50 mg ECT BID 7D Alisertib 50 mg ECT, orally BID for 7 Ddays followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).
Accumulation Ratio (Rac) for Alisertib as Pill in Capsule (PIC) With Once Daily for 14 Days (QD14D) Dosing at Day 14	2.4 ratio Standard Deviation 0.00 • Interval 1.9 to 4.0	1.5 ratio Standard Deviation 0.5 • Interval 1.1 to 4.0	1.9 ratio Standard Deviation 1.6 • Interval 1.9 to 6.0	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Cycle 1 Day 14 predose and at multiple timepoints (up to 8 hours) postdose

Population: PK evaluable population included all participants for whom there were sufficient dosing and alisertib concentration time data to permit non-compartmental PK analysis.

Outcome measures

Outcome measures
Measure	Alisertib 25mg PIC QD 21D n=2 Participants Alisertib 25 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days (D) followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 21D n=5 Participants Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 14D n=6 Participants Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 45 mg PIC QD 14D Alisertib 45 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity to (up 4 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 65 mg PIC QD 14D Alisertib 65 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 90 mg PIC QD 14D Alisertib 90 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT QD 14D Alisertib 40 mg, Enteric-coated Tablet (ECT) formulation, orally, QD for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 30 mg ECT BID 7D Alisertib 30 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT BID 7D alisertib 40 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 50 mg ECT BID 7D Alisertib 50 mg ECT, orally BID for 7 Ddays followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).
Peak/Trough Ratio for Alisertib as Pill in Capsule (PIC) With Once Daily for 14 Days (QD14D) Dosing at Day 14	4.1 ratio Standard Deviation NA • Interval 1.9 to 4.0 Standard deviation was not calculated for 2 participants.	5.4 ratio Standard Deviation 1.9 • Interval 1.1 to 4.0	4.4 ratio Standard Deviation 0.8 • Interval 1.9 to 6.0	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Cycle 1 Day 14 predose and at multiple timepoints (up to 8 hours) postdose

Population: PK evaluable population included all participants for whom there were sufficient dosing and alisertib concentration time data to permit non-compartmental PK analysis.

Outcome measures

Outcome measures
Measure	Alisertib 25mg PIC QD 21D n=2 Participants Alisertib 25 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days (D) followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 21D n=5 Participants Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 14D n=6 Participants Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 45 mg PIC QD 14D Alisertib 45 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity to (up 4 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 65 mg PIC QD 14D Alisertib 65 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 90 mg PIC QD 14D Alisertib 90 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT QD 14D Alisertib 40 mg, Enteric-coated Tablet (ECT) formulation, orally, QD for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 30 mg ECT BID 7D Alisertib 30 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT BID 7D alisertib 40 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 50 mg ECT BID 7D Alisertib 50 mg ECT, orally BID for 7 Ddays followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).
CLss/F: Apparent Oral Clearance at Steady State for Alisertib as Pill in Capsule (PIC) With Once Daily for 14 Days (QD14D) Dosing at Day 14	2.9 L/h Geometric Coefficient of Variation NA • Interval 1.9 to 4.0 Geometric Coefficient of Variation was not calculated for 2 participants.	4.3 L/h Geometric Coefficient of Variation 44 • Interval 1.1 to 4.0	4.3 L/h Geometric Coefficient of Variation 53 • Interval 1.9 to 6.0	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Cycle 1 Day 1 predose and at multiple timepoints (up to 24 hours) postdose

Population: PK evaluable population included all participants for whom there were sufficient dosing and alisertib concentration time data to permit non-compartmental PK analysis.

Outcome measures

Outcome measures
Measure	Alisertib 25mg PIC QD 21D n=6 Participants Alisertib 25 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days (D) followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 21D Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 14D Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 45 mg PIC QD 14D Alisertib 45 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity to (up 4 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 65 mg PIC QD 14D Alisertib 65 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 90 mg PIC QD 14D Alisertib 90 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT QD 14D Alisertib 40 mg, Enteric-coated Tablet (ECT) formulation, orally, QD for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 30 mg ECT BID 7D Alisertib 30 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT BID 7D alisertib 40 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 50 mg ECT BID 7D Alisertib 50 mg ECT, orally BID for 7 Ddays followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).
Cmax: Maximum Observed Concentration for Alisertib as Enteric Coated Tablet (ECT) With Once Daily for 14 Days (QD14D) Dosing at Day 1	1227 nM Geometric Coefficient of Variation 41.3	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Cycle 1 Day 14 predose and at multiple timepoints (up to 8 hours) postdose

Population: PK evaluable population included all participants for whom there were sufficient dosing and alisertib concentration time data to permit non-compartmental PK analysis. Here number of participants analyzed are participants evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure	Alisertib 25mg PIC QD 21D n=2 Participants Alisertib 25 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days (D) followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 21D Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 14D Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 45 mg PIC QD 14D Alisertib 45 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity to (up 4 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 65 mg PIC QD 14D Alisertib 65 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 90 mg PIC QD 14D Alisertib 90 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT QD 14D Alisertib 40 mg, Enteric-coated Tablet (ECT) formulation, orally, QD for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 30 mg ECT BID 7D Alisertib 30 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT BID 7D alisertib 40 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 50 mg ECT BID 7D Alisertib 50 mg ECT, orally BID for 7 Ddays followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).
Cmax: Maximum Observed Concentration for Alisertib as Enteric Coated Tablet (ECT) With Once Daily for 14 Days (QD14D) Dosing at Day 14	1608 nM Geometric Coefficient of Variation NA Geometric Coefficient of Variation was not calculated for 2 participants.	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Cycle 1 Day 1 predose and at multiple timepoints (up to 24 hours) postdose

Population: PK evaluable population included all participants for whom there were sufficient dosing and alisertib concentration time data to permit non-compartmental PK analysis.

Outcome measures

Outcome measures
Measure	Alisertib 25mg PIC QD 21D n=6 Participants Alisertib 25 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days (D) followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 21D Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 14D Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 45 mg PIC QD 14D Alisertib 45 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity to (up 4 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 65 mg PIC QD 14D Alisertib 65 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 90 mg PIC QD 14D Alisertib 90 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT QD 14D Alisertib 40 mg, Enteric-coated Tablet (ECT) formulation, orally, QD for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 30 mg ECT BID 7D Alisertib 30 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT BID 7D alisertib 40 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 50 mg ECT BID 7D Alisertib 50 mg ECT, orally BID for 7 Ddays followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).
Tmax: Time of First Occurrence of Cmax for Alisertib as Enteric Coated Tablet (ECT) With Once Daily for 14 Days (QD14D) Dosing at Day 1	3.9 h Full Range NA • Interval 2.0 to 6.1	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Cycle 1 Day 14 predose and at multiple timepoints (up to 8 hours) postdose

Population: PK evaluable population included all participants for whom there were sufficient dosing and alisertib concentration time data to permit non-compartmental PK analysis. Here number of participants analyzed are participants evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure	Alisertib 25mg PIC QD 21D n=2 Participants Alisertib 25 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days (D) followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 21D Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 14D Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 45 mg PIC QD 14D Alisertib 45 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity to (up 4 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 65 mg PIC QD 14D Alisertib 65 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 90 mg PIC QD 14D Alisertib 90 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT QD 14D Alisertib 40 mg, Enteric-coated Tablet (ECT) formulation, orally, QD for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 30 mg ECT BID 7D Alisertib 30 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT BID 7D alisertib 40 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 50 mg ECT BID 7D Alisertib 50 mg ECT, orally BID for 7 Ddays followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).
Tmax: Time of First Occurrence of Cmax for Alisertib as Enteric Coated Tablet (ECT) With Once Daily for 14 Days (QD14D) Dosing at Day 14	5.0 h Full Range NA • Interval 4.0 to 6.0	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Cycle 1 Day 14 predose and at multiple timepoints (up to 8 hours) postdose

Population: PK evaluable population included all participants for whom there were sufficient dosing and alisertib concentration time data to permit non-compartmental PK analysis. Here number of participants analyzed are participants evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure	Alisertib 25mg PIC QD 21D n=5 Participants Alisertib 25 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days (D) followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 21D Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 14D Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 45 mg PIC QD 14D Alisertib 45 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity to (up 4 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 65 mg PIC QD 14D Alisertib 65 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 90 mg PIC QD 14D Alisertib 90 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT QD 14D Alisertib 40 mg, Enteric-coated Tablet (ECT) formulation, orally, QD for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 30 mg ECT BID 7D Alisertib 30 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT BID 7D alisertib 40 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 50 mg ECT BID 7D Alisertib 50 mg ECT, orally BID for 7 Ddays followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).
AUCt: Area Under the Concentration Time Curve From Time 0 to Time t for Alisertib as Enteric Coated Tablet (ECT) With Once Daily for 14 Days (QD14D) Dosing at Day 14	14306 nM*h Geometric Coefficient of Variation 20.3 • Interval 2.0 to 6.1	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Cycle 1 Day 14 predose and at multiple timepoints (up to 8 hours) postdose

Population: PK evaluable population included all participants for whom there were sufficient dosing and alisertib concentration time data to permit non-compartmental PK analysis. Here number of participants analyzed are participants evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure	Alisertib 25mg PIC QD 21D n=1 Participants Alisertib 25 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days (D) followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 21D Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 14D Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 45 mg PIC QD 14D Alisertib 45 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity to (up 4 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 65 mg PIC QD 14D Alisertib 65 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 90 mg PIC QD 14D Alisertib 90 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT QD 14D Alisertib 40 mg, Enteric-coated Tablet (ECT) formulation, orally, QD for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 30 mg ECT BID 7D Alisertib 30 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT BID 7D alisertib 40 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 50 mg ECT BID 7D Alisertib 50 mg ECT, orally BID for 7 Ddays followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).
Terminal Half Life for Alisertib as Enteric Coated Tablet (ECT) With Once Daily for 14 Days (QD14D) Dosing at Day 14	11.7 h Standard Deviation NA • Interval 2.0 to 6.1 Standard deviation is not estimable for 1 participant.	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Cycle 1 Day 14 predose and at multiple timepoints (up to 8 hours) postdose

Population: PK evaluable population included all participants for whom there were sufficient dosing and alisertib concentration time data to permit non-compartmental PK analysis. Here number of participants analyzed are participants evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure	Alisertib 25mg PIC QD 21D n=1 Participants Alisertib 25 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days (D) followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 21D Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 14D Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 45 mg PIC QD 14D Alisertib 45 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity to (up 4 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 65 mg PIC QD 14D Alisertib 65 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 90 mg PIC QD 14D Alisertib 90 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT QD 14D Alisertib 40 mg, Enteric-coated Tablet (ECT) formulation, orally, QD for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 30 mg ECT BID 7D Alisertib 30 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT BID 7D alisertib 40 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 50 mg ECT BID 7D Alisertib 50 mg ECT, orally BID for 7 Ddays followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).
Peak/Trough Ratio for Alisertib as Enteric Coated Tablet (ECT) With Once Daily for 14 Days (QD14D) Dosing at Day 14	2.1 ratio Standard Deviation NA • Interval 2.0 to 6.1 Standard deviation is not estimable for 1 participant.	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Cycle 1 Day 14 predose and at multiple timepoints (up to 8 hours) postdose

Population: PK evaluable population included all participants for whom there were sufficient dosing and alisertib concentration time data to permit non-compartmental PK analysis. Here number of participants analyzed are participants evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure	Alisertib 25mg PIC QD 21D n=1 Participants Alisertib 25 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days (D) followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 21D Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 14D Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 45 mg PIC QD 14D Alisertib 45 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity to (up 4 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 65 mg PIC QD 14D Alisertib 65 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 90 mg PIC QD 14D Alisertib 90 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT QD 14D Alisertib 40 mg, Enteric-coated Tablet (ECT) formulation, orally, QD for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 30 mg ECT BID 7D Alisertib 30 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT BID 7D alisertib 40 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 50 mg ECT BID 7D Alisertib 50 mg ECT, orally BID for 7 Ddays followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).
CLss/F: Apparent Oral Clearance at Steady State for Alisertib as Enteric Coated Tablet (ECT) With Once Daily for 14 Days (QD14D) Dosing at Day 14	2.5 L/h Standard Deviation NA • Interval 2.0 to 6.1 Standard deviation is not estimable for 1 participant.	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Cycle 1 Day 1 predose and at multiple timepoints (up to 12 hours) postdose

Population: PK evaluable population included all participants for whom there were sufficient dosing and alisertib concentration time data to permit non-compartmental PK analysis.

Outcome measures

Outcome measures
Measure	Alisertib 25mg PIC QD 21D n=3 Participants Alisertib 25 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days (D) followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 21D n=9 Participants Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 14D n=10 Participants Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 45 mg PIC QD 14D Alisertib 45 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity to (up 4 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 65 mg PIC QD 14D Alisertib 65 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 90 mg PIC QD 14D Alisertib 90 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT QD 14D Alisertib 40 mg, Enteric-coated Tablet (ECT) formulation, orally, QD for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 30 mg ECT BID 7D Alisertib 30 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT BID 7D alisertib 40 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 50 mg ECT BID 7D Alisertib 50 mg ECT, orally BID for 7 Ddays followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).
Cmax: Maximum Observed Concentration for Alisertib as Enteric Coated Tablet (ECT) With Twice Daily for 7 Days (BID7D) Dosing at Day 1	886 nM Geometric Coefficient of Variation 39.7	1114 nM Geometric Coefficient of Variation 37.1	1531 nM Geometric Coefficient of Variation 58.4	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Cycle 1 Day 7 predose and at multiple timepoints (up to 12 hours) postdose

Outcome measures

Outcome measures
Measure	Alisertib 25mg PIC QD 21D n=3 Participants Alisertib 25 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days (D) followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 21D n=8 Participants Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 14D n=7 Participants Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 45 mg PIC QD 14D Alisertib 45 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity to (up 4 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 65 mg PIC QD 14D Alisertib 65 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 90 mg PIC QD 14D Alisertib 90 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT QD 14D Alisertib 40 mg, Enteric-coated Tablet (ECT) formulation, orally, QD for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 30 mg ECT BID 7D Alisertib 30 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT BID 7D alisertib 40 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 50 mg ECT BID 7D Alisertib 50 mg ECT, orally BID for 7 Ddays followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).
Cmax: Maximum Observed Concentration for Alisertib as Enteric Coated Tablet (ECT) With Twice Daily for 7 Days (BID7D) Dosing at Day 7	2025 nM Geometric Coefficient of Variation 29.6	2586 nM Geometric Coefficient of Variation 35.7	2058 nM Geometric Coefficient of Variation 44.6	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Cycle 1 Day 1 predose and at multiple timepoints (up to 12 hours) postdose

Outcome measures

Outcome measures
Measure	Alisertib 25mg PIC QD 21D n=3 Participants Alisertib 25 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days (D) followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 21D n=9 Participants Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 14D n=10 Participants Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 45 mg PIC QD 14D Alisertib 45 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity to (up 4 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 65 mg PIC QD 14D Alisertib 65 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 90 mg PIC QD 14D Alisertib 90 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT QD 14D Alisertib 40 mg, Enteric-coated Tablet (ECT) formulation, orally, QD for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 30 mg ECT BID 7D Alisertib 30 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT BID 7D alisertib 40 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 50 mg ECT BID 7D Alisertib 50 mg ECT, orally BID for 7 Ddays followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).
Tmax: Time of First Occurrence of Cmax for Alisertib as Enteric Coated Tablet (ECT) With Twice Daily for 7 Days (BID7D) Dosing at Day 1	2.0 h Full Range 39.7 • Interval 2.0 to 2.0	2.2 h Full Range 37.1 • Interval 2.0 to 6.0	2.0 h Full Range 58.4 • Interval 2.0 to 8.0	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Cycle 1 Day 7 predose and at multiple timepoints (up to 12 hours) postdose

Outcome measures

Outcome measures
Measure	Alisertib 25mg PIC QD 21D n=3 Participants Alisertib 25 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days (D) followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 21D n=8 Participants Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 14D n=7 Participants Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 45 mg PIC QD 14D Alisertib 45 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity to (up 4 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 65 mg PIC QD 14D Alisertib 65 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 90 mg PIC QD 14D Alisertib 90 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT QD 14D Alisertib 40 mg, Enteric-coated Tablet (ECT) formulation, orally, QD for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 30 mg ECT BID 7D Alisertib 30 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT BID 7D alisertib 40 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 50 mg ECT BID 7D Alisertib 50 mg ECT, orally BID for 7 Ddays followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).
Tmax: Time of First Occurrence of Cmax for Alisertib as Enteric Coated Tablet (ECT) With Twice Daily for 7 Days (BID7D) Dosing at Day 7	2.0 h Full Range 39.7 • Interval 2.0 to 2.0	2.2 h Full Range 37.1 • Interval 1.0 to 3.6	2.0 h Full Range 58.4 • Interval 1.3 to 6.0	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Cycle 1 Days 1 predose and at multiple timepoints (up to 12 hours) postdose

Outcome measures

Outcome measures
Measure	Alisertib 25mg PIC QD 21D n=3 Participants Alisertib 25 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days (D) followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 21D n=9 Participants Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 14D n=9 Participants Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 45 mg PIC QD 14D Alisertib 45 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity to (up 4 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 65 mg PIC QD 14D Alisertib 65 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 90 mg PIC QD 14D Alisertib 90 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT QD 14D Alisertib 40 mg, Enteric-coated Tablet (ECT) formulation, orally, QD for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 30 mg ECT BID 7D Alisertib 30 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT BID 7D alisertib 40 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 50 mg ECT BID 7D Alisertib 50 mg ECT, orally BID for 7 Ddays followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).
AUCt: Area Under the Concentration Time Curve From Time 0 to Time t for Alisertib as Enteric Coated Tablet (ECT) With Twice Daily for 7 Days (BID7D) Dosing at Day 1	5518 nM*hr Geometric Coefficient of Variation 18.3	7095 nM*hr Geometric Coefficient of Variation 42.5	9732 nM*hr Geometric Coefficient of Variation 48.5	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Cycle 1 Day 7 predose and at multiple timepoints (up to 12 hours) postdose

Outcome measures

Outcome measures
Measure	Alisertib 25mg PIC QD 21D n=3 Participants Alisertib 25 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days (D) followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 21D n=8 Participants Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 14D n=7 Participants Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 45 mg PIC QD 14D Alisertib 45 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity to (up 4 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 65 mg PIC QD 14D Alisertib 65 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 90 mg PIC QD 14D Alisertib 90 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT QD 14D Alisertib 40 mg, Enteric-coated Tablet (ECT) formulation, orally, QD for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 30 mg ECT BID 7D Alisertib 30 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT BID 7D alisertib 40 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 50 mg ECT BID 7D Alisertib 50 mg ECT, orally BID for 7 Ddays followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).
AUCt: Area Under the Concentration Time Curve From Time 0 to Time t for Alisertib as Enteric Coated Tablet (ECT) With Twice Daily for 7 Days (BID7D) Dosing at Day 7	16024 nM*hr Geometric Coefficient of Variation 20.3	18624 nM*hr Geometric Coefficient of Variation 27.3	17914 nM*hr Geometric Coefficient of Variation 48.6	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Cycle 1 Day 7 predose and at multiple timepoints (up to 12 hours) postdose

Outcome measures

Outcome measures
Measure	Alisertib 25mg PIC QD 21D n=1 Participants Alisertib 25 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days (D) followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 21D n=4 Participants Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 14D n=5 Participants Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 45 mg PIC QD 14D Alisertib 45 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity to (up 4 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 65 mg PIC QD 14D Alisertib 65 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 90 mg PIC QD 14D Alisertib 90 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT QD 14D Alisertib 40 mg, Enteric-coated Tablet (ECT) formulation, orally, QD for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 30 mg ECT BID 7D Alisertib 30 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT BID 7D alisertib 40 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 50 mg ECT BID 7D Alisertib 50 mg ECT, orally BID for 7 Ddays followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).
Terminal Half-Life (t1/2) for Alisertib as Enteric Coated Tablet (ECT) With Twice Daily for 7 Days (BID7D) Dosing at Day 7	13.3 h Standard Deviation NA Standard deviation was not calculated for 2 participants.	19.9 h Standard Deviation 10.7	18.4 h Standard Deviation 13.9	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Cycle 1 Day 7 predose and at multiple timepoints (up to 12 hours) postdose

Outcome measures

Outcome measures
Measure	Alisertib 25mg PIC QD 21D n=3 Participants Alisertib 25 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days (D) followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 21D n=7 Participants Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 14D n=6 Participants Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 45 mg PIC QD 14D Alisertib 45 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity to (up 4 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 65 mg PIC QD 14D Alisertib 65 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 90 mg PIC QD 14D Alisertib 90 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT QD 14D Alisertib 40 mg, Enteric-coated Tablet (ECT) formulation, orally, QD for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 30 mg ECT BID 7D Alisertib 30 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT BID 7D alisertib 40 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 50 mg ECT BID 7D Alisertib 50 mg ECT, orally BID for 7 Ddays followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).
Accumulation Ratio (Rac) for Alisertib as Enteric Coated Tablet (ECT) With Twice Daily for 7 Days (BID7D) Dosing at Day 7	2.9 ratio Standard Deviation 0.5	2.8 ratio Standard Deviation 1.0	2.3 ratio Standard Deviation 0.9	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Cycle 1 Day 7 predose and at multiple timepoints (up to 12 hours) postdose

Outcome measures

Outcome measures
Measure	Alisertib 25mg PIC QD 21D n=3 Participants Alisertib 25 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days (D) followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 21D n=7 Participants Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 14D n=7 Participants Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 45 mg PIC QD 14D Alisertib 45 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity to (up 4 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 65 mg PIC QD 14D Alisertib 65 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 90 mg PIC QD 14D Alisertib 90 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT QD 14D Alisertib 40 mg, Enteric-coated Tablet (ECT) formulation, orally, QD for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 30 mg ECT BID 7D Alisertib 30 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT BID 7D alisertib 40 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 50 mg ECT BID 7D Alisertib 50 mg ECT, orally BID for 7 Ddays followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).
Peak/Trough Ratio for Alisertib as Enteric Coated Tablet (ECT) With Twice Daily for 7 Days (BID7D) Dosing at Day 7	2.5 ratio Standard Deviation 0.6	2.4 ratio Standard Deviation 0.5	2.5 ratio Standard Deviation 2.2	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Cycle 1 Day 7 predose and at multiple timepoints (up to 12 hours) postdose

Outcome measures

Outcome measures
Measure	Alisertib 25mg PIC QD 21D n=3 Participants Alisertib 25 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days (D) followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 21D n=7 Participants Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 14D n=7 Participants Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 45 mg PIC QD 14D Alisertib 45 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity to (up 4 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 65 mg PIC QD 14D Alisertib 65 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 90 mg PIC QD 14D Alisertib 90 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT QD 14D Alisertib 40 mg, Enteric-coated Tablet (ECT) formulation, orally, QD for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 30 mg ECT BID 7D Alisertib 30 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT BID 7D alisertib 40 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 50 mg ECT BID 7D Alisertib 50 mg ECT, orally BID for 7 Ddays followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).
CLss/F: Apparent Oral Clearance at Steady State for Alisertib as Enteric Coated Tablet (ECT) With Twice Daily for 7 Days (BID7D) Dosing at Day 7	3.7 L/h Geometric Coefficient of Variation 0.7	4.4 L/h Geometric Coefficient of Variation 1.9	6.7 L/h Geometric Coefficient of Variation 5.6	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline and every 2 cycles up to Month 12 until disease progression, 30 days after end of treatment (up to 422 days)

Population: The response-evaluable population is defined as all participants who received at least 1 dose of alisertib and have measurable disease at baseline and have at least 1 post baseline response assessment.

Best overall response rate is defined as the percentage of participants with complete response (CR) or partial response (PR) as assessed by the Investigator using International Working Group (IWG) Criteria. CR is defined as the disappearance of all evidence of disease and the definition for PR includes at least a 50% decrease in sum of the product of the diameters and no new lesions.

Outcome measures

Outcome measures
Measure	Alisertib 25mg PIC QD 21D n=23 Participants Alisertib 25 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days (D) followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 21D n=23 Participants Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 14D n=1 Participants Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 45 mg PIC QD 14D Alisertib 45 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity to (up 4 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 65 mg PIC QD 14D Alisertib 65 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 90 mg PIC QD 14D Alisertib 90 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT QD 14D Alisertib 40 mg, Enteric-coated Tablet (ECT) formulation, orally, QD for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 30 mg ECT BID 7D Alisertib 30 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT BID 7D alisertib 40 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 50 mg ECT BID 7D Alisertib 50 mg ECT, orally BID for 7 Ddays followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).
Best Overall Response Rate Based on Investigator's Assessment	13 percentage of participants	9 percentage of participants	100 percentage of participants	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline and every 2 cycles up to Month 12 until disease progression, 30 days after end of treatment (up to 422 days)

Population: Participants from the Response-Evaluable Population who had a response of CR or PR.

DOR is defined as the time from the date of first documentation of a response (either CR or PR) to the date of first documentation of progressive disease (PD) according to International Working Group (IWG) criteria. CR is defined as the disappearance of all evidence of disease and the definition for PR includes at least a 50% decrease in sum of the product of the diameters and no new lesions. PD is defined as any new lesion or increase by \>50% of previously involved sites from nadir.

Outcome measures

Outcome measures
Measure	Alisertib 25mg PIC QD 21D n=3 Participants Alisertib 25 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days (D) followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 21D n=2 Participants Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 14D n=1 Participants Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 45 mg PIC QD 14D Alisertib 45 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity to (up 4 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 65 mg PIC QD 14D Alisertib 65 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 90 mg PIC QD 14D Alisertib 90 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT QD 14D Alisertib 40 mg, Enteric-coated Tablet (ECT) formulation, orally, QD for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 30 mg ECT BID 7D Alisertib 30 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT BID 7D alisertib 40 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 50 mg ECT BID 7D Alisertib 50 mg ECT, orally BID for 7 Ddays followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).
Duration of Response (DOR)	0.03 months Interval 0.03 to 3.65	2.07 months Interval 0.03 to 4.18	0.03 months Interval 0.03 to 0.03	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Cycle 1 Day 1 predose

Population: Safety population included all participants who received any amount of study drug. Data is presented for one arm because the data was collected prior to the participant receiving their assigned treatment.

One peripheral blood sample (approximately 4 mL) was to be obtained on Day 1 of Cycle 1 prior to the first dose of alisertib to genotype participants for polymorphisms in UGT1A1 because UGT1A1 is one of the enzymes responsible for glucuronidation of alisertib, which is expected to contribute to the clearance of alisertib. wt=wild type. \*28=polymorphism in the promoter region of a UGT1A1 allele resulting in reduced UGT1A1 expression. Not determined = blood sample was not evaluable.

Outcome measures

Outcome measures
Measure	Alisertib 25mg PIC QD 21D n=58 Participants Alisertib 25 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days (D) followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 21D Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 21 days followed by a 7-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 2 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 35 mg PIC QD 14D Alisertib 35 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 45 mg PIC QD 14D Alisertib 45 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity to (up 4 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 65 mg PIC QD 14D Alisertib 65 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 90 mg PIC QD 14D Alisertib 90 mg, Powder-in-Capsule (PIC) formulation, orally, once daily (QD) for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 5 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT QD 14D Alisertib 40 mg, Enteric-coated Tablet (ECT) formulation, orally, QD for 14 days followed by a 14-day recovery period in 28-day cycles until disease progression or unacceptable alisertib-related toxicity (up to 3 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 30 mg ECT BID 7D Alisertib 30 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 40 mg ECT BID 7D alisertib 40 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).	Alisertib 50 mg ECT BID 7D Alisertib 50 mg ECT, orally BID for 7 Ddays followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 6 cycles). All participants received an initial starting dosage of alisertib PIC 25 mg, orally, twice daily (BID) on Day 1 (loading dose).
Number of Participants With Polymorphisms in Gene Encoding Enzyme UGT1A1 wt/wt	23 participants	—	—	—	—	—	—	—	—	—
Number of Participants With Polymorphisms in Gene Encoding Enzyme UGT1A1 wt/*28	23 participants	—	—	—	—	—	—	—	—	—
Number of Participants With Polymorphisms in Gene Encoding Enzyme UGT1A1 28/28	8 participants	—	—	—	—	—	—	—	—	—
Number of Participants With Polymorphisms in Gene Encoding Enzyme UGT1A1 other/other	1 participants	—	—	—	—	—	—	—	—	—
Number of Participants With Polymorphisms in Gene Encoding Enzyme UGT1A1 Not Determined	2 participants	—	—	—	—	—	—	—	—	—
Number of Participants With Polymorphisms in Gene Encoding Enzyme UGT1A1 Missing	1 participants	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Cycle 1 Day 1 predose

Population: As per protocol amendment, no data was collected for polymorphisms in Aurora A Kinase.

Outcome measures

Outcome data not reported

Adverse Events

Part 1 PIC Dose Escalation

Serious events: 12 serious events

Other events: 28 other events

Deaths: 0 deaths

Part 1 ECT Dose Escalation

Serious events: 15 serious events

Other events: 28 other events

Deaths: 0 deaths

Part 2 PTCL

Serious events: 2 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Director

Takeda

Phone: +1-877-825-3327

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee In general, Investigators may publish clinical data after the earlier of (i) publication by the Sponsor or (ii) 12 months following the abandonment, early termination or database lock; provided a copy of the publication provided to Sponsor at least 30 days ahead of publication, the Sponsor's confidential information is removed as may be requested by Sponsor and Investigator defers publication for up to 60 days in the event Sponsor provides notice that it intends to file a patent application.
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Restriction type: OTHER