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| ID | Type | Description | Link |
|---|---|---|---|
| VX15-984-001 | Other Identifier | Other |
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| Name | Class |
|---|---|
| Merck KGaA, Darmstadt, Germany | INDUSTRY |
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The purpose of this study was to evaluate the safety and tolerability of VX-984 (M9831) administered alone and in combination with pegylated liposomal doxorubicin (PLD), and to determine the maximum tolerated dose (MTD) and preliminary evidence of efficacy of VX-984 in combination with PLD in participants with advanced solid tumors.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| VX-984 120 mg + PLD 40 mg/m^2 | Experimental |
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| VX-984 240 mg + PLD 40 mg/m^2 | Experimental |
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| VX-984 480 mg + PLD 40 mg/m^2 | Experimental |
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| VX-984 720 mg + PLD 40 mg/m^2 | Experimental |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| VX-984 120 mg + PLD 40 mg/m^2 | Drug | Participants received VX-984 orally 120 milligram (mg) orally 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | 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. | Baseline up to 28 days after the last dose of study treatment, assessed up to 53.1 weeks |
| Part A: Number of Participants Who Experienced Dose Limiting Toxicity (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. | Cycle 1 (each cycle is 28 days) |
| Part A: Number of Participants With Toxicity Grade 3 or Higher in Laboratory Abnormalities | 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. | Baseline up to 28 days after the last dose of study treatment, assessed up to 53.1 weeks |
| Part A: Maximum Tolerated Dose (MTD) of VX-984 in Combination With Pegylated Liposomal Doxorubicin (PLD) |
| Measure | Description | Time Frame |
|---|---|---|
| Part A: Area Under Plasma Concentration (AUC) During a Dosing Interval of VX-984 | AUC is the area under the plasma concentration curve within 1 dosing interval. | 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) |
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Inclusion Criteria:
Participants (male and female for Part A and female for Part B) were at least 18 year of age.
Part A Participants with histologically or cytologically confirmed malignant advanced solid tumors, who had progressed on at least 1 prior chemotherapy, and for whom either
Part B
Measurable disease according to RECIST criteria (Version 1.1)
Life expectancy of at least 12 weeks
Hematological and biochemical indices within acceptable ranges shown at screening.
Normal left ventricular ejection fraction on screening assessed by transthoracic echocardiogram or multiple gated acquisition (MUGA) scan
Exclusion Criteria:
Previous radiotherapy (unless brachytherapy), endocrine therapy, chemotherapy, or exposure to investigational medicinal products during the 4 weeks (6 weeks for nitrosoureas and Mitomycin-C) or 4 drug half-lives before the planned administration of the first dose of study drug, whichever is greater. Previous immunotherapy during the 4 weeks before the planned administration of the first dose of study drug.
For Part B only:
Unresolved toxicity of Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 or greater from previous anti-cancer therapy or radiotherapy
History of spinal cord compression or brain metastases, unless asymptomatic, treated, stable, and not requiring treatment with steroids for at least 4 weeks before the planned administration of the first dose of study drug. Any history of leptomeningeal metastases.
Female participants who was pregnant or lactating at Screening, or planned to become pregnant while on study or within 6 months after the last dose of study drug
Female participants of childbearing potential were adhere to contraception guidelines as outlined in the protocol. Female participants were considered to be of nonchildbearing potential if they had undergone surgical hysterectomy or bilateral oophorectomy or had been amenorrheic for more than 2 years with a screening serum follicle-stimulating hormone (FSH) level within the laboratory's reference range for postmenopausal females
Male participants with pregnant or lactating partners or partners who planned to become pregnant while on study or within 6 months after the planned administration of the last dose of study drug
Major surgery ≤4 weeks before first dose of study drug, or incomplete recovery from a prior major surgical procedure
Cardiac conditions
Prior bone marrow transplant
Extensive radiotherapy (to greater than 15% of bone marrow)
Any other condition that in the investigator's opinion would not make the participant a good candidate for the clinical study,
Part B: Current active malignancies of other types, with the exception of adequately treated cone-biopsied in situ carcinoma of the cervix uteri and basal or squamous cell carcinoma of the skin. Prior cancer in remission for 2 years or more would not be excluded.
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| Name | Affiliation | Role |
|---|---|---|
| Medical Responsible | EMD Serono Research & Development Institute, Inc., a subsidiary of Merck KGaA, Darmstadt, Germany | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Scottsdale | Arizona | 85258 | United States | |||
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Aug 21, 2017 | Jul 24, 2019 |
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| VX-984 240 mg + PLD 40 mg/m^2 | Drug | 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. |
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| VX-984 480 mg + PLD 40 mg/m^2 | Drug | 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. |
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| VX-984 720 mg + PLD 40 mg/m^2 | Drug | 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. |
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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. |
| Up to Cycle 1 Day 28 (each cycle is 28 days) |
| Part A: Number of Participants With Clinical Significant Abnormalities in Vital Signs | 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. | Baseline up to 28 days after the last dose of study treatment, assessed up to 53.1 weeks |
| Part A: Number of Participants With Clinical Significant Abnormalities Echocardiograms | 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. | Baseline up to 28 days after the last dose of study treatment, assessed up to 53.1 weeks |
| Part A: Number of Participants With Clinical Significant Abnormalities in Electrocardiogram(ECG) Parameters | 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. | Baseline up to 28 days after the last dose of study treatment, assessed up to 53.1 weeks |
| Part A: Maximum Observed Plasma Concentration (Cmax) of VX-984 |
Pharmacokinetic PK parameter Cmax was obtained directly from the concentration versus time curve. |
| 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) |
| Part A: Time to Reach Maximum Plasma Concentration (Tmax) of VX-984 | Time to reach the maximum plasma concentration (Tmax) was obtained directly from the concentration versus time curve. | 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) |
| Part A: Minimum Observed Plasma Concentration During Dosing Interval (Cmin) of VX-984 | Cmin is minimum observed plasma concentration obtained directly from the concentration versus time curve. | 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) |
| Part A: Area Under the Plasma Concentration Curve From Time Zero to 96 Hours Post Dose AUC(0-96h) of Pegylated Liposomal Doxorubicin | 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. | Pre-infusion and at 1, 2, 4, 6, 24, 72 and 96 hours after infusion in Cycle 1 (each Cycle is of 28 days) |
| Part A: Maximum Observed Plasma Concentration (Cmax0-96h) From Time Zero to 96 Hours Post Dose of Pegylated Liposomal Doxorubicin | Cmax is the maximum observed plasma concentration obtained directly from concentration versus time curve from zero to 96 hours | Pre-infusion and at 1, 2, 4, 6, 24, 72 and 96 hours after infusion in Cycle 1 (each Cycle is of 28 days) |
| Part A: Time to Reach Maximum Plasma Concentration From Zero to 96 Hours Post Dose (tmax0-96h) of Pegylated Liposomal Doxorubicin | Tmax is time to reach maximum observed plasma concentration obtained directly from the concentration versus time curve from zero to 96 hours post dose. | Pre-infusion and at 1, 2, 4, 6, 24, 72 and 96 hours after infusion in Cycle 1 (each Cycle is of 28 days) |
| Part A: Number of Participants With Best Overall Response Evaluated by Response Criteria Evaluation (RECIST 1.1) | 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. | Up to 2 years |
| Boston |
| Massachusetts |
| 02215 |
| United States |
| Nashville | Tennessee | 37203 | United States |
| Dallas | Texas | 75246 | United States |
| Houston | Texas | 77030 | United States |
| FG001 | 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. |
| FG002 | 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. |
| FG003 | 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. |
| COMPLETED |
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| NOT COMPLETED |
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Full analysis set included all participants who had received at least 1 dose of study treatment.
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 | 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. |
| BG002 | 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. |
| BG003 | 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. |
| BG004 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||
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| Primary | Part A: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs | 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. | The safety analysis set included all participants who had received at least 1 dose of the study treatment. | Posted | Count of Participants | Participants | Baseline up to 28 days after the last dose of study treatment, assessed up to 53.1 weeks |
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| Primary | Part A: Number of Participants Who Experienced Dose Limiting Toxicity (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. | 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. | Posted | Count of Participants | Participants | Cycle 1 (each cycle is 28 days) |
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| Primary | Part A: Number of Participants With Toxicity Grade 3 or Higher in Laboratory Abnormalities | 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. | The safety analysis set included all participants who had received at least 1 dose of the study treatment. | Posted | Count of Participants | Participants | Baseline up to 28 days after the last dose of study treatment, assessed up to 53.1 weeks |
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| Primary | Part A: Maximum Tolerated Dose (MTD) of VX-984 in Combination With Pegylated Liposomal Doxorubicin (PLD) | 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. | 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. | Posted | Number | milligram | Up to Cycle 1 Day 28 (each cycle is 28 days) |
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| Secondary | Part A: Area Under Plasma Concentration (AUC) During a Dosing Interval of VX-984 | AUC is the area under the plasma concentration curve within 1 dosing interval. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram hour per milliliter (ng*h/mL) | 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) |
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| Secondary | Part A: Maximum Observed Plasma Concentration (Cmax) of VX-984 | Pharmacokinetic PK parameter Cmax was obtained directly from the concentration versus time curve. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 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) |
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| Secondary | Part A: Time to Reach Maximum Plasma Concentration (Tmax) of VX-984 | Time to reach the maximum plasma concentration (Tmax) was obtained directly from the concentration versus time curve. | 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. | Posted | Median | Full Range | hours | 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) |
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| Secondary | Part A: Minimum Observed Plasma Concentration During Dosing Interval (Cmin) of VX-984 | Cmin is minimum observed plasma concentration obtained directly from the concentration versus time curve. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 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) |
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| Secondary | Part A: Area Under the Plasma Concentration Curve From Time Zero to 96 Hours Post Dose AUC(0-96h) of Pegylated Liposomal Doxorubicin | 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*h/mL | Pre-infusion and at 1, 2, 4, 6, 24, 72 and 96 hours after infusion in Cycle 1 (each Cycle is of 28 days) |
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| Secondary | Part A: Maximum Observed Plasma Concentration (Cmax0-96h) From Time Zero to 96 Hours Post Dose of Pegylated Liposomal Doxorubicin | Cmax is the maximum observed plasma concentration obtained directly from concentration versus time curve from zero to 96 hours | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Pre-infusion and at 1, 2, 4, 6, 24, 72 and 96 hours after infusion in Cycle 1 (each Cycle is of 28 days) |
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| Secondary | Part A: Time to Reach Maximum Plasma Concentration From Zero to 96 Hours Post Dose (tmax0-96h) of Pegylated Liposomal Doxorubicin | Tmax is time to reach maximum observed plasma concentration obtained directly from the concentration versus time curve from zero to 96 hours post dose. | 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. | Posted | Median | Full Range | Hours | Pre-infusion and at 1, 2, 4, 6, 24, 72 and 96 hours after infusion in Cycle 1 (each Cycle is of 28 days) |
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| Secondary | Part A: Number of Participants With Best Overall Response Evaluated by Response Criteria Evaluation (RECIST 1.1) | 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. | Full analysis set included all participants who had received at least 1 dose of the study treatment. | Posted | Count of Participants | Participants | Up to 2 years |
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| Primary | Part A: Number of Participants With Clinical Significant Abnormalities in Vital Signs | 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. | The safety analysis set included all participants who had received at least 1 dose of the study treatment. | Posted | Count of Participants | Participants | Baseline up to 28 days after the last dose of study treatment, assessed up to 53.1 weeks |
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| Primary | Part A: Number of Participants With Clinical Significant Abnormalities Echocardiograms | 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. | The safety analysis set included all participants who had received at least 1 dose of the study treatment. | Posted | Count of Participants | Participants | Baseline up to 28 days after the last dose of study treatment, assessed up to 53.1 weeks |
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| Primary | Part A: Number of Participants With Clinical Significant Abnormalities in Electrocardiogram(ECG) Parameters | 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. | The safety analysis set included all participants who had received at least 1 dose of the study treatment. | Posted | Count of Participants | Participants | Baseline up to 28 days after the last dose of study treatment, assessed up to 53.1 weeks |
|
Baseline up to 28 days of follow up after the last dose of study treatment, assessed up to 53.1 weeks
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. | 0 | 3 | 2 | 3 | 3 | 3 |
| EG001 | 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. | 0 | 3 | 0 | 3 | 3 | 3 |
| EG002 | 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. | 2 | 6 | 3 | 6 | 6 | 6 |
| EG003 | 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. | 0 | 3 | 1 | 3 | 3 | 3 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain | Gastrointestinal disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Small intestinal obstruction | Gastrointestinal disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Lung infection | Infections and infestations | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Cancer pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Deep vein thrombosis | Vascular disorders | MedDRA version 20.1 | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Iron deficiency anaemia | Blood and lymphatic system disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Leukocytosis | Blood and lymphatic system disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Sinus bradycardia | Cardiac disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Vertigo | Ear and labyrinth disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Vision blurred | Eye disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Abdominal discomfort | Gastrointestinal disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Abdominal distension | Gastrointestinal disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Colitis | Gastrointestinal disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Dysphagia | Gastrointestinal disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Flatulence | Gastrointestinal disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Gastric ulcer | Gastrointestinal disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Haemorrhoids | Gastrointestinal disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Asthenia | General disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Fatigue | General disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Mucosal inflammation | General disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Non-cardiac chest pain | General disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Temperature intolerance | General disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Fungal skin infection | Infections and infestations | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Infection | Infections and infestations | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Lung infection | Infections and infestations | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Oral candidiasis | Infections and infestations | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Pyelonephritis | Infections and infestations | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Blood cholesterol increased | Investigations | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Lymphocyte count decreased | Investigations | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Hypertriglyceridaemia | Metabolism and nutrition disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Muscle tightness | Musculoskeletal and connective tissue disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Soft tissue swelling | Musculoskeletal and connective tissue disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Neuropathy peripheral | Nervous system disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Peripheral sensory neuropathy | Nervous system disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Somnolence | Nervous system disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Delirium | Psychiatric disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Bladder spasm | Renal and urinary disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Chromaturia | Renal and urinary disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Dysuria | Renal and urinary disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Hydronephrosis | Renal and urinary disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Pollakiuria | Renal and urinary disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Urinary incontinence | Renal and urinary disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Dyspareunia | Reproductive system and breast disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Vulvovaginal dryness | Reproductive system and breast disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Hiccups | Respiratory, thoracic and mediastinal disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Nail bed disorder | Skin and subcutaneous tissue disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Palmar-plantar erythrodysaesthesia syndrome | Skin and subcutaneous tissue disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Petechiae | Skin and subcutaneous tissue disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Skin hyperpigmentation | Skin and subcutaneous tissue disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Skin lesion | Skin and subcutaneous tissue disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Skin ulcer | Skin and subcutaneous tissue disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Deep vein thrombosis | Vascular disorders | MedDRA version 20.1 | Non-systematic Assessment |
| |
| Hot flush | Vascular disorders | MedDRA version 20.1 | Non-systematic Assessment |
|
The study was discontinued during dose escalation in Part A, based on business related reasons as decided by the Sponsor. Therefore, the expansion cohorts (Part B) were not conducted. Hence, we have not reported the outcome measure of Part B.
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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Communication Center | Merck KGaA Darmstadt, Germany | +49-6151-72-5200 | service@emdgroup.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jan 26, 2018 | Jul 24, 2019 | SAP_001.pdf |
| ID | Term |
|---|---|
| C041277 | 1-dodecylpyridoxal |
Not provided
Not provided
Not provided
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| Any Serious TEAE |
|
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.
| OG002 | 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. |
| OG003 | 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. |
|
|
| OG002 | 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. |
| OG003 | 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. |
|
|
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.
| OG002 | 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. |
| OG003 | 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. |
|
|
| OG002 | 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. |
| OG003 | 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. |
|
|
| OG002 | 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. |
| OG003 | 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. |
|
|
| OG002 | 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. |
| OG003 | 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. |
|
|
| OG002 | 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. |
| OG003 | 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. |
|
|
| OG002 | 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. |
| OG003 | 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. |
|
|
| OG002 | 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. |
| OG003 | 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. |
|
|
| OG002 | 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. |
| OG003 | 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. |
|
|
| OG001 | 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. |
| OG002 | 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. |
| OG003 | 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. |
|
|
| OG002 | 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. |
| OG003 | 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. |
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| OG002 | 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. |
| OG003 | 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. |
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| OG002 | 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. |
| OG003 | 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. |
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