Trial Outcomes & Findings for First-in-Human Study of the Safety, Tolerability, and Pharmacokinetic/Pharmacodynamic Profile of VX-984 in Combination With Chemotherapy (NCT NCT02644278)

Last Updated: 2019-09-09

Results Overview

An adverse event (AE) was defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A serious AE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Treatment-Emergent adverse events (TEAEs) were defined as AEs that were reported or worsened on or after the start of study drug dosing through the 28-day Safety Follow-up visit. TEAEs included both Serious TEAEs and non-serious TEAEs.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

15 participants

Primary outcome timeframe

Baseline up to 28 days after the last dose of study treatment, assessed up to 53.1 weeks

Results posted on

2019-09-09

Participant Flow

First Participant First Visit: 29 Feb 2016-Last Participant Last Visit: 19-Oct-2017; A total of 15 participants were enrolled in Part A and no participants were enrolled for Part B as the study was discontinued during dose escalation in Part A, based on business related reasons as decided by the Sponsor.

Participant milestones

Participant milestones
Measure	VX-984 120 mg + PLD 40 mg/m^2 Participants received VX-984 orally 120 milligram (mg) once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 120 mg in combination with pegylated liposomal doxorubicin (PLD) 40 milligram per square meter (mg/m\^2) administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.	VX-984 240 mg + PLD 40 mg/m^2 Participants received VX-984 orally 240 mg orally once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 240 mg in combination with PLD 40 mg/m\^2 administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities, withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.	VX-984 480 mg + PLD 40 mg/m^2 Participants received VX-984 orally 480 mg orally once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 480 mg in combination with PLD 40 mg/m\^2 administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities, withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.	VX-984 720 mg + PLD 40 mg/m^2 Participants received VX-984 orally 720 mg orally once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 720 mg in combination with PLD 40 mg/m\^2 administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities, withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.
Overall Study STARTED	3	3	6	3
Overall Study COMPLETED	3	3	6	3
Overall Study NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

First-in-Human Study of the Safety, Tolerability, and Pharmacokinetic/Pharmacodynamic Profile of VX-984 in Combination With Chemotherapy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	VX-984 120 mg + PLD 40 mg/m^2 n=3 Participants Participants received VX-984 orally 120 milligram (mg) once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 120 mg in combination with pegylated liposomal doxorubicin (PLD) 40 milligram per square meter (mg/m\^2) administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.	VX-984 240 mg + PLD 40 mg/m^2 n=3 Participants Participants received VX-984 orally 240 mg orally once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 240 mg in combination with PLD 40 mg/m\^2 administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities, withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.	VX-984 480 mg + PLD 40 mg/m^2 n=6 Participants Participants received VX-984 orally 480 mg orally once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 480 mg in combination with PLD 40 mg/m\^2 administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities, withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.	VX-984 720 mg + PLD 40 mg/m^2 n=3 Participants Participants received VX-984 orally 720 mg orally once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 720 mg in combination with PLD 40 mg/m\^2 administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities, withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.	Total n=15 Participants Total of all reporting groups
Age, Continuous	51.0 Years STANDARD_DEVIATION 17.32 • n=5 Participants	68.7 Years STANDARD_DEVIATION 5.77 • n=7 Participants	57.5 Years STANDARD_DEVIATION 9.09 • n=5 Participants	64.3 Years STANDARD_DEVIATION 8.33 • n=4 Participants	59.8 Years STANDARD_DEVIATION 11.28 • n=21 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants	3 Participants n=4 Participants	14 Participants n=21 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants	3 Participants n=4 Participants	15 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) White	2 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants	3 Participants n=4 Participants	12 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants

PRIMARY outcome

Timeframe: Baseline up to 28 days after the last dose of study treatment, assessed up to 53.1 weeks

Population: The safety analysis set included all participants who had received at least 1 dose of the study treatment.

Outcome measures

Outcome measures
Measure	VX-984 120 mg + PLD 40 mg/m^2 n=3 Participants Participants received VX-984 orally 120 milligram (mg) once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 120 mg in combination with pegylated liposomal doxorubicin (PLD) 40 milligram per square meter (mg/m\^2) administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.	VX-984 240 mg + PLD 40 mg/m^2 n=3 Participants Participants received VX-984 orally 240 mg orally once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 240 mg in combination with PLD 40 mg/m\^2 administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities, withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.	VX-984 480 mg + PLD 40 mg/m^2 n=6 Participants Participants received VX-984 orally 480 mg orally once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 480 mg in combination with PLD 40 mg/m\^2 administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities, withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.	VX-984 720 mg + PLD 40 mg/m^2 n=3 Participants Participants received VX-984 orally 720 mg orally once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 720 mg in combination with PLD 40 mg/m\^2 administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities, withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.
Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs Any TEAE	3 Participants	3 Participants	6 Participants	3 Participants
Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs Any Serious TEAE	2 Participants	0 Participants	3 Participants	1 Participants

PRIMARY outcome

Timeframe: Cycle 1 (each cycle is 28 days)

Population: DLT evaluable set included all participants in the safety analysis set who either met the minimum exposure criterion and had sufficient safety evaluations (as determined by the Investigators and the Sponsor) or have had a DLT.

DLT was defined using National cancer Institute Common Toxicity Criteria for Adverse Events Version 4.0 as any of the following toxicities: Grade 4 neutropenia for more than 7 days; Grade greater than or equal to (\>=) 3 febrile neutropenia; Grade 4 or Grade 3 thrombocytopenia with bleeding. Grade \>= 3 uncontrolled nausea/vomiting and/or diarrhea despite adequate and optimal treatment and Grade \>= 3 any non- hematological adverse event (AE), except the aforementioned gastrointestinal events and alopecia.

Outcome measures

Outcome measures
Measure	VX-984 120 mg + PLD 40 mg/m^2 n=3 Participants Participants received VX-984 orally 120 milligram (mg) once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 120 mg in combination with pegylated liposomal doxorubicin (PLD) 40 milligram per square meter (mg/m\^2) administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.	VX-984 240 mg + PLD 40 mg/m^2 n=3 Participants Participants received VX-984 orally 240 mg orally once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 240 mg in combination with PLD 40 mg/m\^2 administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities, withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.	VX-984 480 mg + PLD 40 mg/m^2 n=5 Participants Participants received VX-984 orally 480 mg orally once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 480 mg in combination with PLD 40 mg/m\^2 administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities, withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.	VX-984 720 mg + PLD 40 mg/m^2 n=3 Participants Participants received VX-984 orally 720 mg orally once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 720 mg in combination with PLD 40 mg/m\^2 administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities, withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.
Part A: Number of Participants Who Experienced Dose Limiting Toxicity (DLT)	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Baseline up to 28 days after the last dose of study treatment, assessed up to 53.1 weeks

Population: The safety analysis set included all participants who had received at least 1 dose of the study treatment.

The laboratory measurements included hematology and serum chemistry. It had been graded according to National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 into Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (Life-threatening) and Grade 5 = death. Participants with grade 3 or higher were reported.

Outcome measures

Outcome measures
Measure	VX-984 120 mg + PLD 40 mg/m^2 n=3 Participants Participants received VX-984 orally 120 milligram (mg) once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 120 mg in combination with pegylated liposomal doxorubicin (PLD) 40 milligram per square meter (mg/m\^2) administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.	VX-984 240 mg + PLD 40 mg/m^2 n=3 Participants Participants received VX-984 orally 240 mg orally once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 240 mg in combination with PLD 40 mg/m\^2 administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities, withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.	VX-984 480 mg + PLD 40 mg/m^2 n=6 Participants Participants received VX-984 orally 480 mg orally once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 480 mg in combination with PLD 40 mg/m\^2 administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities, withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.	VX-984 720 mg + PLD 40 mg/m^2 n=3 Participants Participants received VX-984 orally 720 mg orally once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 720 mg in combination with PLD 40 mg/m\^2 administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities, withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.
Part A: Number of Participants With Toxicity Grade 3 or Higher in Laboratory Abnormalities Participants With Serum Chemistry Abnormalities	1 Participants	1 Participants	2 Participants	1 Participants
Part A: Number of Participants With Toxicity Grade 3 or Higher in Laboratory Abnormalities Participants With Hematology Abnormalities	1 Participants	0 Participants	5 Participants	2 Participants

PRIMARY outcome

Timeframe: Up to Cycle 1 Day 28 (each cycle is 28 days)

The MTD was defined as the combination dose associated with the highest probability that Dose limiting toxicity (DLT) events will occur in 16.6 percent to less than 33.3 percent participants as the combination dose that not exceeded the overdose criterion (more than 25 percent probability that DLT events occurred less than or equal to (\>=) 33 percent of participants. DLT was defined using National Cancer Institute Common Toxicity Criteria for Adverse Events Version 4.0.

Outcome measures

Outcome measures
Measure	VX-984 120 mg + PLD 40 mg/m^2 n=3 Participants Participants received VX-984 orally 120 milligram (mg) once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 120 mg in combination with pegylated liposomal doxorubicin (PLD) 40 milligram per square meter (mg/m\^2) administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.	VX-984 240 mg + PLD 40 mg/m^2 n=3 Participants Participants received VX-984 orally 240 mg orally once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 240 mg in combination with PLD 40 mg/m\^2 administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities, withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.	VX-984 480 mg + PLD 40 mg/m^2 n=5 Participants Participants received VX-984 orally 480 mg orally once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 480 mg in combination with PLD 40 mg/m\^2 administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities, withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.	VX-984 720 mg + PLD 40 mg/m^2 n=3 Participants Participants received VX-984 orally 720 mg orally once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 720 mg in combination with PLD 40 mg/m\^2 administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities, withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.
Part A: Maximum Tolerated Dose (MTD) of VX-984 in Combination With Pegylated Liposomal Doxorubicin (PLD)	NA milligram Due to premature discontinuation of the study, MTD was not determined.	NA milligram Due to premature discontinuation of the study, MTD was not determined.	NA milligram Due to premature discontinuation of the study, MTD was not determined.	NA milligram Due to premature discontinuation of the study, MTD was not determined.

PRIMARY outcome

Timeframe: Baseline up to 28 days after the last dose of study treatment, assessed up to 53.1 weeks

Population: The safety analysis set included all participants who had received at least 1 dose of the study treatment.

Vital signs assessment included blood pressure, pulse rate and body temperature. Clinical significance was determined by the investigator. Number of participants with clinical significant abnormalities in vital Signs reported here.

Outcome measures

Outcome measures
Measure	VX-984 120 mg + PLD 40 mg/m^2 n=3 Participants Participants received VX-984 orally 120 milligram (mg) once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 120 mg in combination with pegylated liposomal doxorubicin (PLD) 40 milligram per square meter (mg/m\^2) administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.	VX-984 240 mg + PLD 40 mg/m^2 n=3 Participants Participants received VX-984 orally 240 mg orally once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 240 mg in combination with PLD 40 mg/m\^2 administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities, withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.	VX-984 480 mg + PLD 40 mg/m^2 n=6 Participants Participants received VX-984 orally 480 mg orally once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 480 mg in combination with PLD 40 mg/m\^2 administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities, withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.	VX-984 720 mg + PLD 40 mg/m^2 n=3 Participants Participants received VX-984 orally 720 mg orally once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 720 mg in combination with PLD 40 mg/m\^2 administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities, withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.
Part A: Number of Participants With Clinical Significant Abnormalities in Vital Signs	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Baseline up to 28 days after the last dose of study treatment, assessed up to 53.1 weeks

Population: The safety analysis set included all participants who had received at least 1 dose of the study treatment.

Echocardiogram is a graphic outline of the heart's movement. Clinical significance was determined by the investigator. Number of participants with clinical significant abnormalities in Echocardiograms reported here.

Outcome measures

Outcome measures
Measure	VX-984 120 mg + PLD 40 mg/m^2 n=3 Participants Participants received VX-984 orally 120 milligram (mg) once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 120 mg in combination with pegylated liposomal doxorubicin (PLD) 40 milligram per square meter (mg/m\^2) administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.	VX-984 240 mg + PLD 40 mg/m^2 n=3 Participants Participants received VX-984 orally 240 mg orally once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 240 mg in combination with PLD 40 mg/m\^2 administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities, withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.	VX-984 480 mg + PLD 40 mg/m^2 n=6 Participants Participants received VX-984 orally 480 mg orally once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 480 mg in combination with PLD 40 mg/m\^2 administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities, withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.	VX-984 720 mg + PLD 40 mg/m^2 n=3 Participants Participants received VX-984 orally 720 mg orally once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 720 mg in combination with PLD 40 mg/m\^2 administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities, withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.
Part A: Number of Participants With Clinical Significant Abnormalities Echocardiograms	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Baseline up to 28 days after the last dose of study treatment, assessed up to 53.1 weeks

Population: The safety analysis set included all participants who had received at least 1 dose of the study treatment.

ECG parameters included heart rate, pulse rate, QRS,QT, RR, QTcB and QTcF. Clinical significance was determined by the investigator. Number of participants with clinical significant abnormalities in ECG parameters reported here.

Outcome measures

Outcome measures
Measure	VX-984 120 mg + PLD 40 mg/m^2 n=3 Participants Participants received VX-984 orally 120 milligram (mg) once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 120 mg in combination with pegylated liposomal doxorubicin (PLD) 40 milligram per square meter (mg/m\^2) administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.	VX-984 240 mg + PLD 40 mg/m^2 n=3 Participants Participants received VX-984 orally 240 mg orally once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 240 mg in combination with PLD 40 mg/m\^2 administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities, withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.	VX-984 480 mg + PLD 40 mg/m^2 n=6 Participants Participants received VX-984 orally 480 mg orally once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 480 mg in combination with PLD 40 mg/m\^2 administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities, withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.	VX-984 720 mg + PLD 40 mg/m^2 n=3 Participants Participants received VX-984 orally 720 mg orally once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 720 mg in combination with PLD 40 mg/m\^2 administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities, withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.
Part A: Number of Participants With Clinical Significant Abnormalities in Electrocardiogram(ECG) Parameters	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Pre-dose and at 0.5, 1, 2, 4, 8, and 24 hours post-dose on Day -12 and Day 4 in Cycle 1; Pre-dose and at 0.5, 1, 2, 4 hours post-dose on Day 2 in Cycle 1 (each Cycle is of 28 days)

Population: The Pharmacokinetic (PK) analysis included all participants who had received at least 1 dose of VX-984 or PLD and provided at least 1 measurable post dose concentration of VX-984 or one measurable post dose concentration of PLD.

AUC is the area under the plasma concentration curve within 1 dosing interval.

Outcome measures

Outcome measures
Measure	VX-984 120 mg + PLD 40 mg/m^2 n=3 Participants Participants received VX-984 orally 120 milligram (mg) once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 120 mg in combination with pegylated liposomal doxorubicin (PLD) 40 milligram per square meter (mg/m\^2) administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.	VX-984 240 mg + PLD 40 mg/m^2 n=3 Participants Participants received VX-984 orally 240 mg orally once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 240 mg in combination with PLD 40 mg/m\^2 administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities, withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.	VX-984 480 mg + PLD 40 mg/m^2 n=6 Participants Participants received VX-984 orally 480 mg orally once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 480 mg in combination with PLD 40 mg/m\^2 administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities, withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.	VX-984 720 mg + PLD 40 mg/m^2 n=3 Participants Participants received VX-984 orally 720 mg orally once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 720 mg in combination with PLD 40 mg/m\^2 administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities, withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.
Part A: Area Under Plasma Concentration (AUC) During a Dosing Interval of VX-984	NA nanogram hour per milliliter (ng*h/mL) Geometric Coefficient of Variation NA Although PK samples were collected, PK samples were not analyzed due to business reasons of no longer developing the compound.	NA nanogram hour per milliliter (ng*h/mL) Geometric Coefficient of Variation NA Although PK samples were collected, PK samples were not analyzed due to business reasons of no longer developing the compound.	NA nanogram hour per milliliter (ng*h/mL) Geometric Coefficient of Variation NA Although PK samples were collected, PK samples were not analyzed due to business reasons of no longer developing the compound.	NA nanogram hour per milliliter (ng*h/mL) Geometric Coefficient of Variation NA Although PK samples were collected, PK samples were not analyzed due to business reasons of no longer developing the compound.

SECONDARY outcome

Timeframe: Pre-dose and at 0.5, 1, 2, 4, 8, and 24 hours post-dose on Day -12 and Day 4 in Cycle 1; Pre-dose and at 0.5, 1, 2, 4 hours post-dose on Day 2 in Cycle 1 (each Cycle is of 28 days)

Pharmacokinetic PK parameter Cmax was obtained directly from the concentration versus time curve.

Outcome measures

Outcome measures
Measure	VX-984 120 mg + PLD 40 mg/m^2 n=3 Participants Participants received VX-984 orally 120 milligram (mg) once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 120 mg in combination with pegylated liposomal doxorubicin (PLD) 40 milligram per square meter (mg/m\^2) administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.	VX-984 240 mg + PLD 40 mg/m^2 n=3 Participants Participants received VX-984 orally 240 mg orally once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 240 mg in combination with PLD 40 mg/m\^2 administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities, withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.	VX-984 480 mg + PLD 40 mg/m^2 n=6 Participants Participants received VX-984 orally 480 mg orally once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 480 mg in combination with PLD 40 mg/m\^2 administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities, withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.	VX-984 720 mg + PLD 40 mg/m^2 n=3 Participants Participants received VX-984 orally 720 mg orally once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 720 mg in combination with PLD 40 mg/m\^2 administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities, withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.
Part A: Maximum Observed Plasma Concentration (Cmax) of VX-984	NA ng/mL Geometric Coefficient of Variation NA Although PK samples were collected, PK samples were not analyzed due to business reasons of no longer developing the compound.	NA ng/mL Geometric Coefficient of Variation NA Although PK samples were collected, PK samples were not analyzed due to business reasons of no longer developing the compound.	NA ng/mL Geometric Coefficient of Variation NA Although PK samples were collected, PK samples were not analyzed due to business reasons of no longer developing the compound.	NA ng/mL Geometric Coefficient of Variation NA Although PK samples were collected, PK samples were not analyzed due to business reasons of no longer developing the compound.

SECONDARY outcome

Timeframe: Pre-dose and at 0.5, 1, 2, 4, 8, and 24 hours post-dose on Day -12 and Day 4 in Cycle 1; Pre-dose and at 0.5, 1, 2, 4 hours post-dose on Day 2 in Cycle 1 (each Cycle is of 28 days)

Time to reach the maximum plasma concentration (Tmax) was obtained directly from the concentration versus time curve.

Outcome measures

Outcome measures
Measure	VX-984 120 mg + PLD 40 mg/m^2 n=3 Participants Participants received VX-984 orally 120 milligram (mg) once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 120 mg in combination with pegylated liposomal doxorubicin (PLD) 40 milligram per square meter (mg/m\^2) administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.	VX-984 240 mg + PLD 40 mg/m^2 n=3 Participants Participants received VX-984 orally 240 mg orally once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 240 mg in combination with PLD 40 mg/m\^2 administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities, withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.	VX-984 480 mg + PLD 40 mg/m^2 n=6 Participants Participants received VX-984 orally 480 mg orally once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 480 mg in combination with PLD 40 mg/m\^2 administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities, withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.	VX-984 720 mg + PLD 40 mg/m^2 n=3 Participants Participants received VX-984 orally 720 mg orally once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 720 mg in combination with PLD 40 mg/m\^2 administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities, withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.
Part A: Time to Reach Maximum Plasma Concentration (Tmax) of VX-984	NA hours Although PK samples were collected, PK samples were not analyzed due to business reasons of no longer developing the compound.	NA hours Although PK samples were collected, PK samples were not analyzed due to business reasons of no longer developing the compound.	NA hours Although PK samples were collected, PK samples were not analyzed due to business reasons of no longer developing the compound.	NA hours Although PK samples were collected, PK samples were not analyzed due to business reasons of no longer developing the compound.

SECONDARY outcome

Timeframe: Pre-dose and at 0.5, 1, 2, 4, 8, and 24 hours post-dose on Day -12 and Day 4 in Cycle 1; Pre-dose and at 0.5, 1, 2, 4 hours post-dose on Day 2 in Cycle 1 (each Cycle is of 28 days)

Cmin is minimum observed plasma concentration obtained directly from the concentration versus time curve.

Outcome measures

Outcome measures
Measure	VX-984 120 mg + PLD 40 mg/m^2 n=3 Participants Participants received VX-984 orally 120 milligram (mg) once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 120 mg in combination with pegylated liposomal doxorubicin (PLD) 40 milligram per square meter (mg/m\^2) administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.	VX-984 240 mg + PLD 40 mg/m^2 n=3 Participants Participants received VX-984 orally 240 mg orally once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 240 mg in combination with PLD 40 mg/m\^2 administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities, withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.	VX-984 480 mg + PLD 40 mg/m^2 n=6 Participants Participants received VX-984 orally 480 mg orally once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 480 mg in combination with PLD 40 mg/m\^2 administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities, withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.	VX-984 720 mg + PLD 40 mg/m^2 n=3 Participants Participants received VX-984 orally 720 mg orally once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 720 mg in combination with PLD 40 mg/m\^2 administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities, withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.
Part A: Minimum Observed Plasma Concentration During Dosing Interval (Cmin) of VX-984	NA ng/mL Geometric Coefficient of Variation NA Although PK samples were collected, PK samples were not analyzed due to business reasons of no longer developing the compound.	NA ng/mL Geometric Coefficient of Variation NA Although PK samples were collected, PK samples were not analyzed due to business reasons of no longer developing the compound.	NA ng/mL Geometric Coefficient of Variation NA Although PK samples were collected, PK samples were not analyzed due to business reasons of no longer developing the compound.	NA ng/mL Geometric Coefficient of Variation NA Although PK samples were collected, PK samples were not analyzed due to business reasons of no longer developing the compound.

SECONDARY outcome

Timeframe: Pre-infusion and at 1, 2, 4, 6, 24, 72 and 96 hours after infusion in Cycle 1 (each Cycle is of 28 days)

The AUC(0-96h) was estimated by determining the total area under the curve of the concentration versus curve extrapolated from 0 to 96 hours.

Outcome measures

Outcome measures
Measure	VX-984 120 mg + PLD 40 mg/m^2 n=3 Participants Participants received VX-984 orally 120 milligram (mg) once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 120 mg in combination with pegylated liposomal doxorubicin (PLD) 40 milligram per square meter (mg/m\^2) administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.	VX-984 240 mg + PLD 40 mg/m^2 n=3 Participants Participants received VX-984 orally 240 mg orally once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 240 mg in combination with PLD 40 mg/m\^2 administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities, withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.	VX-984 480 mg + PLD 40 mg/m^2 n=6 Participants Participants received VX-984 orally 480 mg orally once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 480 mg in combination with PLD 40 mg/m\^2 administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities, withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.	VX-984 720 mg + PLD 40 mg/m^2 n=3 Participants Participants received VX-984 orally 720 mg orally once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 720 mg in combination with PLD 40 mg/m\^2 administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities, withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.
Part A: Area Under the Plasma Concentration Curve From Time Zero to 96 Hours Post Dose AUC(0-96h) of Pegylated Liposomal Doxorubicin	NA ng*h/mL Geometric Coefficient of Variation NA Although PK samples were collected, PK samples were not analyzed due to business reasons of no longer developing the compound.	NA ng*h/mL Geometric Coefficient of Variation NA Although PK samples were collected, PK samples were not analyzed due to business reasons of no longer developing the compound.	NA ng*h/mL Geometric Coefficient of Variation NA Although PK samples were collected, PK samples were not analyzed due to business reasons of no longer developing the compound.	NA ng*h/mL Geometric Coefficient of Variation NA Although PK samples were collected, PK samples were not analyzed due to business reasons of no longer developing the compound.

SECONDARY outcome

Timeframe: Pre-infusion and at 1, 2, 4, 6, 24, 72 and 96 hours after infusion in Cycle 1 (each Cycle is of 28 days)

Cmax is the maximum observed plasma concentration obtained directly from concentration versus time curve from zero to 96 hours

Outcome measures

Outcome measures
Measure	VX-984 120 mg + PLD 40 mg/m^2 n=3 Participants Participants received VX-984 orally 120 milligram (mg) once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 120 mg in combination with pegylated liposomal doxorubicin (PLD) 40 milligram per square meter (mg/m\^2) administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.	VX-984 240 mg + PLD 40 mg/m^2 n=3 Participants Participants received VX-984 orally 240 mg orally once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 240 mg in combination with PLD 40 mg/m\^2 administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities, withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.	VX-984 480 mg + PLD 40 mg/m^2 n=6 Participants Participants received VX-984 orally 480 mg orally once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 480 mg in combination with PLD 40 mg/m\^2 administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities, withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.	VX-984 720 mg + PLD 40 mg/m^2 n=3 Participants Participants received VX-984 orally 720 mg orally once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 720 mg in combination with PLD 40 mg/m\^2 administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities, withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.
Part A: Maximum Observed Plasma Concentration (Cmax0-96h) From Time Zero to 96 Hours Post Dose of Pegylated Liposomal Doxorubicin	NA ng/mL Geometric Coefficient of Variation NA Although PK samples were collected, PK samples were not analyzed due to business reasons of no longer developing the compound.	NA ng/mL Geometric Coefficient of Variation NA Although PK samples were collected, PK samples were not analyzed due to business reasons of no longer developing the compound.	NA ng/mL Geometric Coefficient of Variation NA Although PK samples were collected, PK samples were not analyzed due to business reasons of no longer developing the compound.	NA ng/mL Geometric Coefficient of Variation NA Although PK samples were collected, PK samples were not analyzed due to business reasons of no longer developing the compound.

SECONDARY outcome

Timeframe: Pre-infusion and at 1, 2, 4, 6, 24, 72 and 96 hours after infusion in Cycle 1 (each Cycle is of 28 days)

Tmax is time to reach maximum observed plasma concentration obtained directly from the concentration versus time curve from zero to 96 hours post dose.

Outcome measures

Outcome measures
Measure	VX-984 120 mg + PLD 40 mg/m^2 n=3 Participants Participants received VX-984 orally 120 milligram (mg) once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 120 mg in combination with pegylated liposomal doxorubicin (PLD) 40 milligram per square meter (mg/m\^2) administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.	VX-984 240 mg + PLD 40 mg/m^2 n=3 Participants Participants received VX-984 orally 240 mg orally once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 240 mg in combination with PLD 40 mg/m\^2 administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities, withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.	VX-984 480 mg + PLD 40 mg/m^2 n=6 Participants Participants received VX-984 orally 480 mg orally once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 480 mg in combination with PLD 40 mg/m\^2 administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities, withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.	VX-984 720 mg + PLD 40 mg/m^2 n=3 Participants Participants received VX-984 orally 720 mg orally once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 720 mg in combination with PLD 40 mg/m\^2 administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities, withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.
Part A: Time to Reach Maximum Plasma Concentration From Zero to 96 Hours Post Dose (tmax0-96h) of Pegylated Liposomal Doxorubicin	NA Hours Although PK samples were collected, PK samples were not analyzed due to business reasons of no longer developing the compound.	NA Hours Although PK samples were collected, PK samples were not analyzed due to business reasons of no longer developing the compound.	NA Hours Although PK samples were collected, PK samples were not analyzed due to business reasons of no longer developing the compound.	NA Hours Although PK samples were collected, PK samples were not analyzed due to business reasons of no longer developing the compound.

SECONDARY outcome

Timeframe: Up to 2 years

Population: Full analysis set included all participants who had received at least 1 dose of the study treatment.

The best overall response was defined as the number of participants who had achieved complete response (CR) or partial response (PR) as the best overall response according to radiological assessments as adjudicated by the IRC from randomization until the first occurrence of progressive disease (PD). CR: Complete Response (CR) defined as disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. Partial response (PR) defined as at least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters. PD defined as an increase of at least 20% in the sum of the diameters of target lesions, taking as reference the smallest sum of the diameters of target lesions recorded since treatment started.

Outcome measures

Outcome measures
Measure	VX-984 120 mg + PLD 40 mg/m^2 n=3 Participants Participants received VX-984 orally 120 milligram (mg) once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 120 mg in combination with pegylated liposomal doxorubicin (PLD) 40 milligram per square meter (mg/m\^2) administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.	VX-984 240 mg + PLD 40 mg/m^2 n=3 Participants Participants received VX-984 orally 240 mg orally once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 240 mg in combination with PLD 40 mg/m\^2 administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities, withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.	VX-984 480 mg + PLD 40 mg/m^2 n=6 Participants Participants received VX-984 orally 480 mg orally once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 480 mg in combination with PLD 40 mg/m\^2 administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities, withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.	VX-984 720 mg + PLD 40 mg/m^2 n=3 Participants Participants received VX-984 orally 720 mg orally once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 720 mg in combination with PLD 40 mg/m\^2 administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities, withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.
Part A: Number of Participants With Best Overall Response Evaluated by Response Criteria Evaluation (RECIST 1.1) Stable disease	1 Participants	0 Participants	4 Participants	1 Participants
Part A: Number of Participants With Best Overall Response Evaluated by Response Criteria Evaluation (RECIST 1.1) Progressive disease	0 Participants	3 Participants	0 Participants	1 Participants
Part A: Number of Participants With Best Overall Response Evaluated by Response Criteria Evaluation (RECIST 1.1) Complete Response	0 Participants	0 Participants	0 Participants	0 Participants
Part A: Number of Participants With Best Overall Response Evaluated by Response Criteria Evaluation (RECIST 1.1) Partial Response	1 Participants	0 Participants	0 Participants	0 Participants
Part A: Number of Participants With Best Overall Response Evaluated by Response Criteria Evaluation (RECIST 1.1) Not evaluable	1 Participants	0 Participants	2 Participants	1 Participants

Adverse Events

VX-984 120 mg + PLD 40 mg/m^2

Serious events: 2 serious events

Other events: 3 other events

Deaths: 0 deaths

VX-984 240 mg + PLD 40 mg/m^2

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

VX-984 480 mg + PLD 40 mg/m^2

Serious events: 3 serious events

Other events: 6 other events

Deaths: 2 deaths

VX-984 720 mg + PLD 40 mg/m^2

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	VX-984 120 mg + PLD 40 mg/m^2 n=3 participants at risk Participants received VX-984 orally 120 milligram (mg) once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 120 mg in combination with pegylated liposomal doxorubicin (PLD) 40 milligram per square meter (mg/m\^2) administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.	VX-984 240 mg + PLD 40 mg/m^2 n=3 participants at risk Participants received VX-984 orally 240 mg orally once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 240 mg in combination with PLD 40 mg/m\^2 administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities, withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.	VX-984 480 mg + PLD 40 mg/m^2 n=6 participants at risk Participants received VX-984 orally 480 mg orally once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 480 mg in combination with PLD 40 mg/m\^2 administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities, withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.	VX-984 720 mg + PLD 40 mg/m^2 n=3 participants at risk Participants received VX-984 orally 720 mg orally once daily alone on Days -14 to -12 of a 14-day Lead-in Period, followed by VX-984 720 mg in combination with PLD 40 mg/m\^2 administered intravenous infusion, with PLD administered on Day 1 and VX-984 administered on Day 2 to Day 4 for up to six 28-day cycle or until disease progression unacceptable toxicities, withdrawal of consent, or until exposure to PLD exceeded 550 mg/m\^2.
Gastrointestinal disorders Abdominal pain	66.7% 2/3 • Baseline up to 28 days of follow up after the last dose of study treatment, assessed up to 53.1 weeks	0.00% 0/3 • Baseline up to 28 days of follow up after the last dose of study treatment, assessed up to 53.1 weeks	0.00% 0/6 • Baseline up to 28 days of follow up after the last dose of study treatment, assessed up to 53.1 weeks	0.00% 0/3 • Baseline up to 28 days of follow up after the last dose of study treatment, assessed up to 53.1 weeks
Gastrointestinal disorders Nausea	33.3% 1/3 • Baseline up to 28 days of follow up after the last dose of study treatment, assessed up to 53.1 weeks	0.00% 0/3 • Baseline up to 28 days of follow up after the last dose of study treatment, assessed up to 53.1 weeks	16.7% 1/6 • Baseline up to 28 days of follow up after the last dose of study treatment, assessed up to 53.1 weeks	0.00% 0/3 • Baseline up to 28 days of follow up after the last dose of study treatment, assessed up to 53.1 weeks
Gastrointestinal disorders Small intestinal obstruction	33.3% 1/3 • Baseline up to 28 days of follow up after the last dose of study treatment, assessed up to 53.1 weeks	0.00% 0/3 • Baseline up to 28 days of follow up after the last dose of study treatment, assessed up to 53.1 weeks	0.00% 0/6 • Baseline up to 28 days of follow up after the last dose of study treatment, assessed up to 53.1 weeks	33.3% 1/3 • Baseline up to 28 days of follow up after the last dose of study treatment, assessed up to 53.1 weeks
Infections and infestations Lung infection	0.00% 0/3 • Baseline up to 28 days of follow up after the last dose of study treatment, assessed up to 53.1 weeks	0.00% 0/3 • Baseline up to 28 days of follow up after the last dose of study treatment, assessed up to 53.1 weeks	16.7% 1/6 • Baseline up to 28 days of follow up after the last dose of study treatment, assessed up to 53.1 weeks	0.00% 0/3 • Baseline up to 28 days of follow up after the last dose of study treatment, assessed up to 53.1 weeks
Infections and infestations Sepsis	0.00% 0/3 • Baseline up to 28 days of follow up after the last dose of study treatment, assessed up to 53.1 weeks	0.00% 0/3 • Baseline up to 28 days of follow up after the last dose of study treatment, assessed up to 53.1 weeks	16.7% 1/6 • Baseline up to 28 days of follow up after the last dose of study treatment, assessed up to 53.1 weeks	0.00% 0/3 • Baseline up to 28 days of follow up after the last dose of study treatment, assessed up to 53.1 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer pain	33.3% 1/3 • Baseline up to 28 days of follow up after the last dose of study treatment, assessed up to 53.1 weeks	0.00% 0/3 • Baseline up to 28 days of follow up after the last dose of study treatment, assessed up to 53.1 weeks	0.00% 0/6 • Baseline up to 28 days of follow up after the last dose of study treatment, assessed up to 53.1 weeks	0.00% 0/3 • Baseline up to 28 days of follow up after the last dose of study treatment, assessed up to 53.1 weeks
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/3 • Baseline up to 28 days of follow up after the last dose of study treatment, assessed up to 53.1 weeks	0.00% 0/3 • Baseline up to 28 days of follow up after the last dose of study treatment, assessed up to 53.1 weeks	16.7% 1/6 • Baseline up to 28 days of follow up after the last dose of study treatment, assessed up to 53.1 weeks	0.00% 0/3 • Baseline up to 28 days of follow up after the last dose of study treatment, assessed up to 53.1 weeks
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/3 • Baseline up to 28 days of follow up after the last dose of study treatment, assessed up to 53.1 weeks	0.00% 0/3 • Baseline up to 28 days of follow up after the last dose of study treatment, assessed up to 53.1 weeks	16.7% 1/6 • Baseline up to 28 days of follow up after the last dose of study treatment, assessed up to 53.1 weeks	0.00% 0/3 • Baseline up to 28 days of follow up after the last dose of study treatment, assessed up to 53.1 weeks
Vascular disorders Deep vein thrombosis	0.00% 0/3 • Baseline up to 28 days of follow up after the last dose of study treatment, assessed up to 53.1 weeks	0.00% 0/3 • Baseline up to 28 days of follow up after the last dose of study treatment, assessed up to 53.1 weeks	16.7% 1/6 • Baseline up to 28 days of follow up after the last dose of study treatment, assessed up to 53.1 weeks	0.00% 0/3 • Baseline up to 28 days of follow up after the last dose of study treatment, assessed up to 53.1 weeks

Other adverse events

Additional Information

Communication Center

Merck KGaA Darmstadt, Germany

Phone: +49-6151-72-5200

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee A copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested in writing, such publication will be withheld for up to an additional 60 days.
Publication restrictions are in place

Restriction type: OTHER