Various Advanced Cancer
Conditions
Brief summary
The purpose of this study is to determine the safety and effectiveness of nivolumab alone and in combination with ipilimumab in pediatric patients with high grade primary central nervous system (CNS) malignancies.
Interventions
Specified dose on specified days
Specified dose on specified days
Sponsors
Study design
Eligibility
Inclusion criteria
* Must have received standard of care therapy, and there must be no potentially-curative treatment available, in one of the following cohorts: * A newly diagnosed Diffuse Intrinsic Pontine Glioma (DIPG) that has been treated with radiation therapy (RT) but no chemotherapy * A histologically confirmed recurrent or progressive non-brainstem High Grade Glioma (HGG) previously treated with surgical resection and RT * A histologically confirmed medulloblastoma that has relapsed or is resistant to at least one line of prior therapy including surgery, RT, and chemotherapy * A histologically confirmed ependymoma that has relapsed or is resistant to at least one line of prior therapy including surgical resection and RT * A histologically-confirmed high grade CNS malignancy other than above which is recurrent or progressive after at least one line of prior therapy * Lansky play score (LPS) for ≤ 16 years of age or Karnofsky performance scale (KPS) for \> 16 years of age assessed within two weeks of enrollment must be \>= 60 * A tumor sample must be available for submission to central laboratory (not required for DIPG)
Exclusion criteria
* An active, known, or suspected autoimmune disease * A concurrent condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of start of study treatment * Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS). Other protocol defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Safety Lead-In Participants With Dose Limiting Toxicities (DLTs) | up to 6 weeks post-dosing | A dose-limiting toxicity (DLT) is defined as a drug-related AE occurring in the first 6 weeks of study treatment. A participant was considered evaluable for a DLT if study treatment was delayed \> 2 weeks or was discontinued due to a related Adverse Event (AE), or if planned study treatment (3 doses of nivolumab in Module A, 2 doses of nivolumab plus ipilimumab in Module B) was administered and safety evaluation after 6 weeks on study is available to the study steering committee (SSC). |
| Number of Safety Lead-In Participants With Serious Adverse Events (SAEs) | up to 6 weeks post-dosing | The number of Safety Lead-In Participants who experienced a Serious Adverse Event (SAE) during the course of the study. |
| Number of Safety Lead-In Participants With Adverse Events (AEs) Leading to Discontinuation | From first dose to 30 days post-last dose (up to approximately 6 weeks) | The number of Safety Lead-In Participants who experienced an Adverse Event (AE) during the course of the study that lead to discontinuation of study therapy. |
| Overall Survival (OS), Cohort 1 Only | up to approximately 42 months | Overall survival (OS) is defined as the time between the date of diagnosis and the date of death in Cohort 1. |
| Progression-Free Survival (PFS), Cohorts 2-4 | up to approximately 42 months | Progression-free survival (PFS) is defined as the time from first dose to the date of the first documented tumor progression or death due to any cause. |
| Progression-Free Survival (PFS), Cohort 5 Only | up to approximately 42 months | Progression-free survival (PFS) is defined as the time from first dose to the date of the first documented tumor progression or death due to any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Treated Participants With Drug-Related Adverse Events | From first dose to 30 days post-last dose (up to approximately an average of 3 months and a maximum of 51 months) | The number of treated participants who experienced a Drug-Related Adverse Event during the course of the study. An AE is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. |
| Number of Treated Participants With Adverse Events Leading to Discontinuation | From first dose to 30 days post-last dose (up to approximately an average of 3 months and a maximum of 51 months) | The number of treated participants who experienced an Adverse Event leading to discontinuation during the course of the study. An AE is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. |
| Progression-Free Survival (PFS), Cohort 1 Only | From first dose to the date of the first documented tumor progression or death due to any cause (up to approximately 55 months) | Progression-free survival (PFS) is defined as the time from first dose to the date of the first documented tumor progression or death due to any cause. Progression is defined as: * ≥ 25% increase in sum of the products of perpendicular diameters of enhancing lesions compared with the smallest tumor measurement * Significant increase in T2 or fast fluid-attenuated inversion recovery (FLAIR) non-enhancing lesions on stable or increasing doses of corticosteroids * Any new lesion * Clear clinical deterioration not attributable to other causes apart from the tumor * Failure to return for evaluation as a result of death or deteriorating condition * Clear progression of non-measurable disease |
| Number of Treated Participant With Laboratory Abnormalities - Liver | From first dose to 30 days post-last dose (up to approximately an average of 3 months and a maximum of 51 months) | The number of treated participants who experienced a laboratory abnormality of the liver during the course of the study. Aspartate aminotransferase (AST) Alanine aminotransferase (ALT) Upper Limit of Normal (ULN) Units per Liter (U/L) Results reported in International System of Units (SI) |
| Number of Treated Participant With Laboratory Abnormalities - Thyroid | From first dose to 30 days post-last dose (up to approximately an average of 3 months and a maximum of 51 months) | The number of treated participants who experienced a laboratory abnormality of the thyroid during the course of the study. Free T3 (FT3) Free T4 (FT4) Thyroid stimulating hormone (TSH) Lower Limit of Normal (LLN) Upper limit of normal (ULN) Milliunits per Liter (mlU/L) Results reported in International System of Units (SI) |
| Number of Treated Participant Deaths | From first dose to the date of death (up to approximately 55 months) | The number of treated participants who died during the course of the study. |
| Overall Survival at 12 Months (OS12), Cohorts 1-4 | From first dose to up to 12 months after first dose | Overall survival at 12 months (OS12) is defined as the percentage of participants who are alive at 12 months, measured as the survival rate at 12 months from Kaplan-Meier product limit cumulative probability. |
| Progression-Free Survival at 6 Months (PFS6), Cohorts 2-5 | From first dose to up to 6 months after first dose | Progression-free survival at 6 months (PFS6) is defined as the percentage of participants who are progression free and alive at 6 months following first dose date, measured as the survival rate at 6 months from Kaplan-Meier product limit cumulative probability of progression free. Progression is defined as: * ≥ 25% increase in sum of the products of perpendicular diameters of enhancing lesions compared with the smallest tumor measurement * Significant increase in T2 or fast fluid-attenuated inversion recovery (FLAIR) non-enhancing lesions on stable or increasing doses of corticosteroids * Any new lesion * Clear clinical deterioration not attributable to other causes apart from the tumor * Failure to return for evaluation as a result of death or deteriorating condition * Clear progression of non-measurable disease |
| Overall Survival (OS), Cohorts 2-5 | From first dose to the date of death (up to approximately 55 months) | Overall survival (OS) is defined as the time between date of first dose and the date of death for Cohorts 2-5. |
| Number of Treated Participants With Adverse Events (AEs) | From first dose to 30 days post-last dose (up to approximately an average of 3 months and a maximum of 51 months) | The number of treated participants who experienced an Adverse Event (AE) during the course of the study. An AE is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. |
| Number of Treated Participants With Serious Adverse Events (SAEs) | From first dose to 30 days post-last dose (up to approximately an average of 3 months and a maximum of 51 months) | The number of treated participants who experienced a Serious Adverse Event (SAE) during the course of the study. SAE is defined as any untoward medical occurrence that, at any dose: * Results in death * Is life-threatening * Requires inpatient hospitalization or causes prolongation of existing hospitalization * Results in persistent or significant disability/incapacity * Is a congenital anomaly/birth defect * Is an important medical event Note: The reporting timeframe of the SAEs for this Outcome Measure (first dose to 30 days post last dose) differs than that of the reporting timeframe of the SAEs reported under the AE section of the results form (first dose to 100 days post last dose) and thus, the data in each table of SAEs reflects the specific timeframe applied. |
Countries
Australia, Brazil, Canada, France, Germany, Hong Kong, Israel, Netherlands, Norway, Poland, Russia, Spain, Sweden, United Kingdom, United States
Participant flow
Pre-assignment details
166 participants were treated
Participants by arm
| Arm | Count |
|---|---|
| Arm A1 Module A: nivolumab 3 mg/kg every 2 weeks.
Cohort 1: participants with newly-diagnosed DIPG, including midline glioma with H3K27M mutation. | 23 |
| Arm B1 Module B: nivolumab 3 mg/kg + ipilimumab 1 mg/kg every 3 weeks, for 4 doses, then nivolumab 3 mg/kg every 2 weeks thereafter.
Cohort 1: participants with newly-diagnosed DIPG, including midline glioma with H3K27M mutation. | 22 |
| Arm A2 Module A: nivolumab 3 mg/kg every 2 weeks.
Cohort 2: participants with recurrent or progressive non-brainstem HGG, regardless of mutation status, including glioblastoma. | 16 |
| Arm B2 Module B: nivolumab 3 mg/kg + ipilimumab 1 mg/kg every 3 weeks, for 4 doses, then nivolumab 3 mg/kg every 2 weeks thereafter.
Cohort 2: participants with recurrent or progressive non-brainstem HGG, regardless of mutation status, including glioblastoma. | 15 |
| Arm A3 Module A: nivolumab 3 mg/kg every 2 weeks.
Cohort 3: participants with relapsed or resistant medulloblastoma. | 15 |
| Arm B3 Module B: nivolumab 3 mg/kg + ipilimumab 1 mg/kg every 3 weeks, for 4 doses, then nivolumab 3 mg/kg every 2 weeks thereafter.
Cohort 3: participants with relapsed or resistant medulloblastoma. | 15 |
| Arm A4 Module A: nivolumab 3 mg/kg every 2 weeks.
Cohort 4: participants with relapsed or resistant ependymoma. | 12 |
| Arm B4 Module B: nivolumab 3 mg/kg + ipilimumab 1 mg/kg every 3 weeks, for 4 doses, then nivolumab 3 mg/kg every 2 weeks thereafter.
Cohort 4: participants with relapsed or resistant ependymoma. | 10 |
| Arm A5 Module A: nivolumab 3 mg/kg every 2 weeks.
Cohort 5: participants with other recurrent subtypes of high-grade CNS malignancy (eg, pineoblastoma, AT/RT, germ cell tumor, and others). | 19 |
| Arm B5 Module B: nivolumab 3 mg/kg + ipilimumab 1 mg/kg every 3 weeks, for 4 doses, then nivolumab 3 mg/kg every 2 weeks thereafter.
Cohort 5: participants with other recurrent subtypes of high-grade CNS malignancy (eg, pineoblastoma, AT/RT, germ cell tumor, and others). | 19 |
| Total | 166 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Administrative reason by sponsor | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Adverse Event unrelated to drug | 0 | 0 | 1 | 1 | 1 | 0 | 1 | 0 | 1 | 1 |
| Overall Study | Disease progression | 19 | 7 | 12 | 7 | 12 | 3 | 6 | 3 | 15 | 8 |
| Overall Study | Lost to Follow-up | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Not reported | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 1 |
| Overall Study | Other reasons | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 |
| Overall Study | Participant withdrew consent | 0 | 1 | 0 | 2 | 1 | 0 | 0 | 0 | 0 | 2 |
| Overall Study | Study drug toxicity | 2 | 2 | 1 | 2 | 1 | 1 | 3 | 0 | 3 | 3 |
| Overall Study | Subject request to discontinue therapy | 0 | 0 | 1 | 1 | 0 | 0 | 1 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Arm A1 | Total | Arm B5 | Arm A5 | Arm B4 | Arm A4 | Arm B3 | Arm A3 | Arm B2 | Arm A2 | Arm B1 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized >= 12 and < 18 years old | 6 Participants | 61 Participants | 6 Participants | 4 Participants | 3 Participants | 3 Participants | 9 Participants | 11 Participants | 8 Participants | 6 Participants | 5 Participants |
| Age, Customized >= 18 years old | 2 Participants | 15 Participants | 0 Participants | 1 Participants | 2 Participants | 1 Participants | 2 Participants | 0 Participants | 2 Participants | 4 Participants | 1 Participants |
| Age, Customized >= 2 and < 12 years old | 15 Participants | 87 Participants | 12 Participants | 13 Participants | 4 Participants | 8 Participants | 4 Participants | 4 Participants | 5 Participants | 6 Participants | 16 Participants |
| Age, Customized < 2 years old | 0 Participants | 3 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 14 Participants | 0 Participants | 2 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 2 Participants | 2 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 60 Participants | 6 Participants | 8 Participants | 5 Participants | 5 Participants | 4 Participants | 6 Participants | 5 Participants | 4 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 14 Participants | 92 Participants | 13 Participants | 9 Participants | 4 Participants | 6 Participants | 10 Participants | 9 Participants | 8 Participants | 10 Participants | 9 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 10 Participants | 2 Participants | 0 Participants | 1 Participants | 3 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Black or African American | 2 Participants | 9 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 4 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 14 Participants | 4 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 4 Participants |
| Race/Ethnicity, Customized White | 19 Participants | 132 Participants | 13 Participants | 18 Participants | 9 Participants | 7 Participants | 14 Participants | 14 Participants | 14 Participants | 13 Participants | 11 Participants |
| Sex: Female, Male Female | 12 Participants | 70 Participants | 10 Participants | 4 Participants | 3 Participants | 6 Participants | 5 Participants | 5 Participants | 3 Participants | 6 Participants | 16 Participants |
| Sex: Female, Male Male | 11 Participants | 96 Participants | 9 Participants | 15 Participants | 7 Participants | 6 Participants | 10 Participants | 10 Participants | 12 Participants | 10 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 18 / 23 | 18 / 22 | 12 / 16 | 13 / 15 | 12 / 15 | 11 / 15 | 9 / 12 | 7 / 10 | 18 / 19 | 15 / 19 |
| other Total, other adverse events | 22 / 23 | 21 / 22 | 15 / 16 | 14 / 15 | 14 / 15 | 14 / 15 | 11 / 12 | 10 / 10 | 18 / 19 | 18 / 19 |
| serious Total, serious adverse events | 17 / 23 | 16 / 22 | 13 / 16 | 12 / 15 | 7 / 15 | 10 / 15 | 11 / 12 | 6 / 10 | 14 / 19 | 15 / 19 |
Outcome results
Number of Safety Lead-In Participants With Adverse Events (AEs) Leading to Discontinuation
The number of Safety Lead-In Participants who experienced an Adverse Event (AE) during the course of the study that lead to discontinuation of study therapy.
Time frame: From first dose to 30 days post-last dose (up to approximately 6 weeks)
Population: Safety Lead-in participants: In Module A, the first 6 DLT-evaluable participants in Cohort 1 and the first 10 DLT-evaluable participants in Cohorts 2-5; in Module B, the first 10 DLT-evaluable participants.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A1, Safety Lead-in | Number of Safety Lead-In Participants With Adverse Events (AEs) Leading to Discontinuation | 3 Participants |
| Arms A2-A5, Safety Lead-in | Number of Safety Lead-In Participants With Adverse Events (AEs) Leading to Discontinuation | 4 Participants |
| Arms B2-B5, Safety Lead-in | Number of Safety Lead-In Participants With Adverse Events (AEs) Leading to Discontinuation | 2 Participants |
Number of Safety Lead-In Participants With Dose Limiting Toxicities (DLTs)
A dose-limiting toxicity (DLT) is defined as a drug-related AE occurring in the first 6 weeks of study treatment. A participant was considered evaluable for a DLT if study treatment was delayed \> 2 weeks or was discontinued due to a related Adverse Event (AE), or if planned study treatment (3 doses of nivolumab in Module A, 2 doses of nivolumab plus ipilimumab in Module B) was administered and safety evaluation after 6 weeks on study is available to the study steering committee (SSC).
Time frame: up to 6 weeks post-dosing
Population: Safety Lead-in participants: In Module A, the first 6 DLT-evaluable participants in Cohort 1 and the first 10 DLT-evaluable participants in Cohorts 2-5; in Module B, the first 10 DLT-evaluable participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A1, Safety Lead-in | Number of Safety Lead-In Participants With Dose Limiting Toxicities (DLTs) | 0 Number of participants |
| Arms A2-A5, Safety Lead-in | Number of Safety Lead-In Participants With Dose Limiting Toxicities (DLTs) | 0 Number of participants |
| Arms B2-B5, Safety Lead-in | Number of Safety Lead-In Participants With Dose Limiting Toxicities (DLTs) | 0 Number of participants |
Number of Safety Lead-In Participants With Serious Adverse Events (SAEs)
The number of Safety Lead-In Participants who experienced a Serious Adverse Event (SAE) during the course of the study.
Time frame: up to 6 weeks post-dosing
Population: Safety Lead-in participants: In Module A, the first 6 DLT-evaluable participants in Cohort 1 and the first 10 DLT-evaluable participants in Cohorts 2-5; in Module B, the first 10 DLT-evaluable participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A1, Safety Lead-in | Number of Safety Lead-In Participants With Serious Adverse Events (SAEs) | 7 Number of participants |
| Arms A2-A5, Safety Lead-in | Number of Safety Lead-In Participants With Serious Adverse Events (SAEs) | 6 Number of participants |
| Arms B2-B5, Safety Lead-in | Number of Safety Lead-In Participants With Serious Adverse Events (SAEs) | 8 Number of participants |
Overall Survival (OS), Cohort 1 Only
Overall survival (OS) is defined as the time between the date of diagnosis and the date of death in Cohort 1.
Time frame: up to approximately 42 months
Population: All treated participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A1, Safety Lead-in | Overall Survival (OS), Cohort 1 Only | 11.66 months |
| Arms A2-A5, Safety Lead-in | Overall Survival (OS), Cohort 1 Only | 10.78 months |
Progression-Free Survival (PFS), Cohort 5 Only
Progression-free survival (PFS) is defined as the time from first dose to the date of the first documented tumor progression or death due to any cause.
Time frame: up to approximately 42 months
Population: All treated participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A1, Safety Lead-in | Progression-Free Survival (PFS), Cohort 5 Only | 1.22 months |
| Arms A2-A5, Safety Lead-in | Progression-Free Survival (PFS), Cohort 5 Only | 1.61 months |
Progression-Free Survival (PFS), Cohorts 2-4
Progression-free survival (PFS) is defined as the time from first dose to the date of the first documented tumor progression or death due to any cause.
Time frame: up to approximately 42 months
Population: All treated participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A1, Safety Lead-in | Progression-Free Survival (PFS), Cohorts 2-4 | 1.74 months |
| Arms A2-A5, Safety Lead-in | Progression-Free Survival (PFS), Cohorts 2-4 | 1.31 months |
| Arms B2-B5, Safety Lead-in | Progression-Free Survival (PFS), Cohorts 2-4 | 1.38 months |
| Arm B3 | Progression-Free Survival (PFS), Cohorts 2-4 | 2.76 months |
| Arm A4 | Progression-Free Survival (PFS), Cohorts 2-4 | 1.41 months |
| Arm B4 | Progression-Free Survival (PFS), Cohorts 2-4 | 4.60 months |
Number of Treated Participant Deaths
The number of treated participants who died during the course of the study.
Time frame: From first dose to the date of death (up to approximately 55 months)
Population: All treated participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A1, Safety Lead-in | Number of Treated Participant Deaths | 18 Participants |
| Arms A2-A5, Safety Lead-in | Number of Treated Participant Deaths | 18 Participants |
| Arms B2-B5, Safety Lead-in | Number of Treated Participant Deaths | 12 Participants |
| Arm B3 | Number of Treated Participant Deaths | 13 Participants |
| Arm A4 | Number of Treated Participant Deaths | 12 Participants |
| Arm B4 | Number of Treated Participant Deaths | 11 Participants |
| Arm A4 | Number of Treated Participant Deaths | 9 Participants |
| Arm B4 | Number of Treated Participant Deaths | 7 Participants |
| Arm A5 | Number of Treated Participant Deaths | 18 Participants |
| Arm B5 | Number of Treated Participant Deaths | 15 Participants |
Number of Treated Participants With Adverse Events (AEs)
The number of treated participants who experienced an Adverse Event (AE) during the course of the study. An AE is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug.
Time frame: From first dose to 30 days post-last dose (up to approximately an average of 3 months and a maximum of 51 months)
Population: All treated participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A1, Safety Lead-in | Number of Treated Participants With Adverse Events (AEs) | 23 Participants |
| Arms A2-A5, Safety Lead-in | Number of Treated Participants With Adverse Events (AEs) | 21 Participants |
| Arms B2-B5, Safety Lead-in | Number of Treated Participants With Adverse Events (AEs) | 15 Participants |
| Arm B3 | Number of Treated Participants With Adverse Events (AEs) | 14 Participants |
| Arm A4 | Number of Treated Participants With Adverse Events (AEs) | 14 Participants |
| Arm B4 | Number of Treated Participants With Adverse Events (AEs) | 15 Participants |
| Arm A4 | Number of Treated Participants With Adverse Events (AEs) | 12 Participants |
| Arm B4 | Number of Treated Participants With Adverse Events (AEs) | 10 Participants |
| Arm A5 | Number of Treated Participants With Adverse Events (AEs) | 18 Participants |
| Arm B5 | Number of Treated Participants With Adverse Events (AEs) | 18 Participants |
Number of Treated Participants With Adverse Events Leading to Discontinuation
The number of treated participants who experienced an Adverse Event leading to discontinuation during the course of the study. An AE is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug.
Time frame: From first dose to 30 days post-last dose (up to approximately an average of 3 months and a maximum of 51 months)
Population: All treated participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A1, Safety Lead-in | Number of Treated Participants With Adverse Events Leading to Discontinuation | 4 Participants |
| Arms A2-A5, Safety Lead-in | Number of Treated Participants With Adverse Events Leading to Discontinuation | 7 Participants |
| Arms B2-B5, Safety Lead-in | Number of Treated Participants With Adverse Events Leading to Discontinuation | 3 Participants |
| Arm B3 | Number of Treated Participants With Adverse Events Leading to Discontinuation | 5 Participants |
| Arm A4 | Number of Treated Participants With Adverse Events Leading to Discontinuation | 2 Participants |
| Arm B4 | Number of Treated Participants With Adverse Events Leading to Discontinuation | 3 Participants |
| Arm A4 | Number of Treated Participants With Adverse Events Leading to Discontinuation | 6 Participants |
| Arm B4 | Number of Treated Participants With Adverse Events Leading to Discontinuation | 1 Participants |
| Arm A5 | Number of Treated Participants With Adverse Events Leading to Discontinuation | 6 Participants |
| Arm B5 | Number of Treated Participants With Adverse Events Leading to Discontinuation | 8 Participants |
Number of Treated Participants With Drug-Related Adverse Events
The number of treated participants who experienced a Drug-Related Adverse Event during the course of the study. An AE is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug.
Time frame: From first dose to 30 days post-last dose (up to approximately an average of 3 months and a maximum of 51 months)
Population: All treated participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A1, Safety Lead-in | Number of Treated Participants With Drug-Related Adverse Events | 14 Participants |
| Arms A2-A5, Safety Lead-in | Number of Treated Participants With Drug-Related Adverse Events | 16 Participants |
| Arms B2-B5, Safety Lead-in | Number of Treated Participants With Drug-Related Adverse Events | 12 Participants |
| Arm B3 | Number of Treated Participants With Drug-Related Adverse Events | 8 Participants |
| Arm A4 | Number of Treated Participants With Drug-Related Adverse Events | 6 Participants |
| Arm B4 | Number of Treated Participants With Drug-Related Adverse Events | 11 Participants |
| Arm A4 | Number of Treated Participants With Drug-Related Adverse Events | 6 Participants |
| Arm B4 | Number of Treated Participants With Drug-Related Adverse Events | 6 Participants |
| Arm A5 | Number of Treated Participants With Drug-Related Adverse Events | 11 Participants |
| Arm B5 | Number of Treated Participants With Drug-Related Adverse Events | 10 Participants |
Number of Treated Participants With Serious Adverse Events (SAEs)
The number of treated participants who experienced a Serious Adverse Event (SAE) during the course of the study. SAE is defined as any untoward medical occurrence that, at any dose: * Results in death * Is life-threatening * Requires inpatient hospitalization or causes prolongation of existing hospitalization * Results in persistent or significant disability/incapacity * Is a congenital anomaly/birth defect * Is an important medical event Note: The reporting timeframe of the SAEs for this Outcome Measure (first dose to 30 days post last dose) differs than that of the reporting timeframe of the SAEs reported under the AE section of the results form (first dose to 100 days post last dose) and thus, the data in each table of SAEs reflects the specific timeframe applied.
Time frame: From first dose to 30 days post-last dose (up to approximately an average of 3 months and a maximum of 51 months)
Population: All treated participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A1, Safety Lead-in | Number of Treated Participants With Serious Adverse Events (SAEs) | 10 Participants |
| Arms A2-A5, Safety Lead-in | Number of Treated Participants With Serious Adverse Events (SAEs) | 14 Participants |
| Arms B2-B5, Safety Lead-in | Number of Treated Participants With Serious Adverse Events (SAEs) | 10 Participants |
| Arm B3 | Number of Treated Participants With Serious Adverse Events (SAEs) | 9 Participants |
| Arm A4 | Number of Treated Participants With Serious Adverse Events (SAEs) | 6 Participants |
| Arm B4 | Number of Treated Participants With Serious Adverse Events (SAEs) | 7 Participants |
| Arm A4 | Number of Treated Participants With Serious Adverse Events (SAEs) | 7 Participants |
| Arm B4 | Number of Treated Participants With Serious Adverse Events (SAEs) | 5 Participants |
| Arm A5 | Number of Treated Participants With Serious Adverse Events (SAEs) | 13 Participants |
| Arm B5 | Number of Treated Participants With Serious Adverse Events (SAEs) | 14 Participants |
Number of Treated Participant With Laboratory Abnormalities - Liver
The number of treated participants who experienced a laboratory abnormality of the liver during the course of the study. Aspartate aminotransferase (AST) Alanine aminotransferase (ALT) Upper Limit of Normal (ULN) Units per Liter (U/L) Results reported in International System of Units (SI)
Time frame: From first dose to 30 days post-last dose (up to approximately an average of 3 months and a maximum of 51 months)
Population: All treated participants
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm A1, Safety Lead-in | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT OR AST > 10XULN | 2 Participants |
| Arm A1, Safety Lead-in | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT OR AST > 20XULN | 0 Participants |
| Arm A1, Safety Lead-in | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT or AST > 3xULN w/ Tbili > 1.5*ULN within 30 days | 0 Participants |
| Arm A1, Safety Lead-in | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT or AST > 3xULN w/ Tbili > 2*ULN within 30 days | 0 Participants |
| Arm A1, Safety Lead-in | Number of Treated Participant With Laboratory Abnormalities - Liver | TOTAL BILIRUBIN > 2XULN | 0 Participants |
| Arm A1, Safety Lead-in | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT or AST > 3xULN w/ Tbili > 2*ULN within 1 day | 0 Participants |
| Arm A1, Safety Lead-in | Number of Treated Participant With Laboratory Abnormalities - Liver | ALP > 1.5XULN | 0 Participants |
| Arm A1, Safety Lead-in | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT OR AST > 3XULN | 3 Participants |
| Arm A1, Safety Lead-in | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT OR AST > 5XULN | 2 Participants |
| Arm A1, Safety Lead-in | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT or AST > 3xULN w/ Tbili > 1.5*ULN within 1 day | 0 Participants |
| Arms A2-A5, Safety Lead-in | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT OR AST > 20XULN | 1 Participants |
| Arms A2-A5, Safety Lead-in | Number of Treated Participant With Laboratory Abnormalities - Liver | TOTAL BILIRUBIN > 2XULN | 2 Participants |
| Arms A2-A5, Safety Lead-in | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT OR AST > 10XULN | 1 Participants |
| Arms A2-A5, Safety Lead-in | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT or AST > 3xULN w/ Tbili > 1.5*ULN within 30 days | 2 Participants |
| Arms A2-A5, Safety Lead-in | Number of Treated Participant With Laboratory Abnormalities - Liver | ALP > 1.5XULN | 0 Participants |
| Arms A2-A5, Safety Lead-in | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT or AST > 3xULN w/ Tbili > 2*ULN within 30 days | 2 Participants |
| Arms A2-A5, Safety Lead-in | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT or AST > 3xULN w/ Tbili > 1.5*ULN within 1 day | 1 Participants |
| Arms A2-A5, Safety Lead-in | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT OR AST > 5XULN | 4 Participants |
| Arms A2-A5, Safety Lead-in | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT OR AST > 3XULN | 7 Participants |
| Arms A2-A5, Safety Lead-in | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT or AST > 3xULN w/ Tbili > 2*ULN within 1 day | 1 Participants |
| Arms B2-B5, Safety Lead-in | Number of Treated Participant With Laboratory Abnormalities - Liver | TOTAL BILIRUBIN > 2XULN | 0 Participants |
| Arms B2-B5, Safety Lead-in | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT OR AST > 3XULN | 2 Participants |
| Arms B2-B5, Safety Lead-in | Number of Treated Participant With Laboratory Abnormalities - Liver | ALP > 1.5XULN | 0 Participants |
| Arms B2-B5, Safety Lead-in | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT OR AST > 20XULN | 1 Participants |
| Arms B2-B5, Safety Lead-in | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT or AST > 3xULN w/ Tbili > 1.5*ULN within 1 day | 1 Participants |
| Arms B2-B5, Safety Lead-in | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT or AST > 3xULN w/ Tbili > 1.5*ULN within 30 days | 1 Participants |
| Arms B2-B5, Safety Lead-in | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT OR AST > 10XULN | 1 Participants |
| Arms B2-B5, Safety Lead-in | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT or AST > 3xULN w/ Tbili > 2*ULN within 1 day | 0 Participants |
| Arms B2-B5, Safety Lead-in | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT or AST > 3xULN w/ Tbili > 2*ULN within 30 days | 0 Participants |
| Arms B2-B5, Safety Lead-in | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT OR AST > 5XULN | 1 Participants |
| Arm B3 | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT or AST > 3xULN w/ Tbili > 2*ULN within 1 day | 0 Participants |
| Arm B3 | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT OR AST > 3XULN | 0 Participants |
| Arm B3 | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT or AST > 3xULN w/ Tbili > 2*ULN within 30 days | 0 Participants |
| Arm B3 | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT OR AST > 5XULN | 0 Participants |
| Arm B3 | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT or AST > 3xULN w/ Tbili > 1.5*ULN within 30 days | 0 Participants |
| Arm B3 | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT or AST > 3xULN w/ Tbili > 1.5*ULN within 1 day | 0 Participants |
| Arm B3 | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT OR AST > 20XULN | 0 Participants |
| Arm B3 | Number of Treated Participant With Laboratory Abnormalities - Liver | TOTAL BILIRUBIN > 2XULN | 0 Participants |
| Arm B3 | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT OR AST > 10XULN | 0 Participants |
| Arm A4 | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT or AST > 3xULN w/ Tbili > 1.5*ULN within 30 days | 0 Participants |
| Arm A4 | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT or AST > 3xULN w/ Tbili > 1.5*ULN within 1 day | 0 Participants |
| Arm A4 | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT OR AST > 20XULN | 0 Participants |
| Arm A4 | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT or AST > 3xULN w/ Tbili > 2*ULN within 1 day | 0 Participants |
| Arm A4 | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT OR AST > 5XULN | 0 Participants |
| Arm A4 | Number of Treated Participant With Laboratory Abnormalities - Liver | TOTAL BILIRUBIN > 2XULN | 0 Participants |
| Arm A4 | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT OR AST > 3XULN | 0 Participants |
| Arm A4 | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT or AST > 3xULN w/ Tbili > 2*ULN within 30 days | 0 Participants |
| Arm A4 | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT OR AST > 10XULN | 0 Participants |
| Arm B4 | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT OR AST > 10XULN | 1 Participants |
| Arm B4 | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT or AST > 3xULN w/ Tbili > 2*ULN within 1 day | 0 Participants |
| Arm B4 | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT or AST > 3xULN w/ Tbili > 1.5*ULN within 1 day | 0 Participants |
| Arm B4 | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT or AST > 3xULN w/ Tbili > 2*ULN within 30 days | 0 Participants |
| Arm B4 | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT OR AST > 5XULN | 1 Participants |
| Arm B4 | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT OR AST > 3XULN | 3 Participants |
| Arm B4 | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT OR AST > 20XULN | 0 Participants |
| Arm B4 | Number of Treated Participant With Laboratory Abnormalities - Liver | TOTAL BILIRUBIN > 2XULN | 0 Participants |
| Arm B4 | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT or AST > 3xULN w/ Tbili > 1.5*ULN within 30 days | 0 Participants |
| Arm A4 | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT or AST > 3xULN w/ Tbili > 1.5*ULN within 1 day | 0 Participants |
| Arm A4 | Number of Treated Participant With Laboratory Abnormalities - Liver | TOTAL BILIRUBIN > 2XULN | 0 Participants |
| Arm A4 | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT or AST > 3xULN w/ Tbili > 1.5*ULN within 30 days | 0 Participants |
| Arm A4 | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT or AST > 3xULN w/ Tbili > 2*ULN within 1 day | 0 Participants |
| Arm A4 | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT or AST > 3xULN w/ Tbili > 2*ULN within 30 days | 0 Participants |
| Arm A4 | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT OR AST > 3XULN | 1 Participants |
| Arm A4 | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT OR AST > 5XULN | 0 Participants |
| Arm A4 | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT OR AST > 10XULN | 0 Participants |
| Arm A4 | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT OR AST > 20XULN | 0 Participants |
| Arm B4 | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT or AST > 3xULN w/ Tbili > 2*ULN within 1 day | 0 Participants |
| Arm B4 | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT OR AST > 5XULN | 1 Participants |
| Arm B4 | Number of Treated Participant With Laboratory Abnormalities - Liver | TOTAL BILIRUBIN > 2XULN | 0 Participants |
| Arm B4 | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT OR AST > 3XULN | 1 Participants |
| Arm B4 | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT or AST > 3xULN w/ Tbili > 2*ULN within 30 days | 0 Participants |
| Arm B4 | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT or AST > 3xULN w/ Tbili > 1.5*ULN within 30 days | 0 Participants |
| Arm B4 | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT or AST > 3xULN w/ Tbili > 1.5*ULN within 1 day | 0 Participants |
| Arm B4 | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT OR AST > 20XULN | 0 Participants |
| Arm B4 | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT OR AST > 10XULN | 1 Participants |
| Arm A5 | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT or AST > 3xULN w/ Tbili > 1.5*ULN within 1 day | 0 Participants |
| Arm A5 | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT or AST > 3xULN w/ Tbili > 2*ULN within 30 days | 0 Participants |
| Arm A5 | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT OR AST > 20XULN | 0 Participants |
| Arm A5 | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT or AST > 3xULN w/ Tbili > 1.5*ULN within 30 days | 0 Participants |
| Arm A5 | Number of Treated Participant With Laboratory Abnormalities - Liver | ALP > 1.5XULN | 0 Participants |
| Arm A5 | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT OR AST > 5XULN | 2 Participants |
| Arm A5 | Number of Treated Participant With Laboratory Abnormalities - Liver | TOTAL BILIRUBIN > 2XULN | 1 Participants |
| Arm A5 | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT OR AST > 10XULN | 2 Participants |
| Arm A5 | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT or AST > 3xULN w/ Tbili > 2*ULN within 1 day | 0 Participants |
| Arm A5 | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT OR AST > 3XULN | 3 Participants |
| Arm B5 | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT OR AST > 3XULN | 2 Participants |
| Arm B5 | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT or AST > 3xULN w/ Tbili > 2*ULN within 1 day | 1 Participants |
| Arm B5 | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT OR AST > 5XULN | 2 Participants |
| Arm B5 | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT or AST > 3xULN w/ Tbili > 1.5*ULN within 30 days | 1 Participants |
| Arm B5 | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT or AST > 3xULN w/ Tbili > 1.5*ULN within 1 day | 1 Participants |
| Arm B5 | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT OR AST > 10XULN | 2 Participants |
| Arm B5 | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT OR AST > 20XULN | 2 Participants |
| Arm B5 | Number of Treated Participant With Laboratory Abnormalities - Liver | ALP > 1.5XULN | 1 Participants |
| Arm B5 | Number of Treated Participant With Laboratory Abnormalities - Liver | TOTAL BILIRUBIN > 2XULN | 1 Participants |
| Arm B5 | Number of Treated Participant With Laboratory Abnormalities - Liver | ALT or AST > 3xULN w/ Tbili > 2*ULN within 30 days | 1 Participants |
Number of Treated Participant With Laboratory Abnormalities - Thyroid
The number of treated participants who experienced a laboratory abnormality of the thyroid during the course of the study. Free T3 (FT3) Free T4 (FT4) Thyroid stimulating hormone (TSH) Lower Limit of Normal (LLN) Upper limit of normal (ULN) Milliunits per Liter (mlU/L) Results reported in International System of Units (SI)
Time frame: From first dose to 30 days post-last dose (up to approximately an average of 3 months and a maximum of 51 months)
Population: All treated participants with at least one on-treatment TSH measurement
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm A1, Safety Lead-in | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH < LLN, WITH TSH >= LLN AT BASELINE | 3 Participants |
| Arm A1, Safety Lead-in | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH > ULN | 2 Participants |
| Arm A1, Safety Lead-in | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH > ULN, WITH TSH <= ULN AT BASELINE | 2 Participants |
| Arm A1, Safety Lead-in | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH < LLN, WITH FT3/FT4 TEST MISSING | 2 Participants |
| Arm A1, Safety Lead-in | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH > ULN, WITH AT LEAST ONE FT3/FT4 TEST < LLN | 1 Participants |
| Arm A1, Safety Lead-in | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH > ULN, WITH ALL OTHER FT3/FT4 TEST >= LLN | 0 Participants |
| Arm A1, Safety Lead-in | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH < LLN, WITH ALL OTHER FT3/FT4 TEST <= ULN | 1 Participants |
| Arm A1, Safety Lead-in | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH > ULN, WITH FT3/FT4 TEST MISSING | 1 Participants |
| Arm A1, Safety Lead-in | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH < LLN | 3 Participants |
| Arm A1, Safety Lead-in | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH<LLN, LLN WITH AT LEAST ONE FT3/FT4 TEST>ULN | 0 Participants |
| Arms A2-A5, Safety Lead-in | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH < LLN, WITH ALL OTHER FT3/FT4 TEST <= ULN | 2 Participants |
| Arms A2-A5, Safety Lead-in | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH > ULN, WITH FT3/FT4 TEST MISSING | 0 Participants |
| Arms A2-A5, Safety Lead-in | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH > ULN | 1 Participants |
| Arms A2-A5, Safety Lead-in | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH < LLN, WITH FT3/FT4 TEST MISSING | 4 Participants |
| Arms A2-A5, Safety Lead-in | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH < LLN | 7 Participants |
| Arms A2-A5, Safety Lead-in | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH > ULN, WITH AT LEAST ONE FT3/FT4 TEST < LLN | 1 Participants |
| Arms A2-A5, Safety Lead-in | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH > ULN, WITH TSH <= ULN AT BASELINE | 1 Participants |
| Arms A2-A5, Safety Lead-in | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH > ULN, WITH ALL OTHER FT3/FT4 TEST >= LLN | 0 Participants |
| Arms A2-A5, Safety Lead-in | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH<LLN, LLN WITH AT LEAST ONE FT3/FT4 TEST>ULN | 1 Participants |
| Arms A2-A5, Safety Lead-in | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH < LLN, WITH TSH >= LLN AT BASELINE | 6 Participants |
| Arms B2-B5, Safety Lead-in | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH > ULN, WITH ALL OTHER FT3/FT4 TEST >= LLN | 1 Participants |
| Arms B2-B5, Safety Lead-in | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH < LLN | 2 Participants |
| Arms B2-B5, Safety Lead-in | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH > ULN, WITH AT LEAST ONE FT3/FT4 TEST < LLN | 1 Participants |
| Arms B2-B5, Safety Lead-in | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH > ULN, WITH TSH <= ULN AT BASELINE | 2 Participants |
| Arms B2-B5, Safety Lead-in | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH > ULN | 3 Participants |
| Arms B2-B5, Safety Lead-in | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH<LLN, LLN WITH AT LEAST ONE FT3/FT4 TEST>ULN | 0 Participants |
| Arms B2-B5, Safety Lead-in | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH > ULN, WITH FT3/FT4 TEST MISSING | 1 Participants |
| Arms B2-B5, Safety Lead-in | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH < LLN, WITH TSH >= LLN AT BASELINE | 1 Participants |
| Arms B2-B5, Safety Lead-in | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH < LLN, WITH FT3/FT4 TEST MISSING | 1 Participants |
| Arms B2-B5, Safety Lead-in | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH < LLN, WITH ALL OTHER FT3/FT4 TEST <= ULN | 1 Participants |
| Arm B3 | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH > ULN, WITH TSH <= ULN AT BASELINE | 1 Participants |
| Arm B3 | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH < LLN, WITH FT3/FT4 TEST MISSING | 0 Participants |
| Arm B3 | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH > ULN, WITH ALL OTHER FT3/FT4 TEST >= LLN | 0 Participants |
| Arm B3 | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH > ULN, WITH FT3/FT4 TEST MISSING | 0 Participants |
| Arm B3 | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH > ULN, WITH AT LEAST ONE FT3/FT4 TEST < LLN | 1 Participants |
| Arm B3 | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH < LLN | 2 Participants |
| Arm B3 | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH < LLN, WITH ALL OTHER FT3/FT4 TEST <= ULN | 2 Participants |
| Arm B3 | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH<LLN, LLN WITH AT LEAST ONE FT3/FT4 TEST>ULN | 0 Participants |
| Arm B3 | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH > ULN | 1 Participants |
| Arm B3 | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH < LLN, WITH TSH >= LLN AT BASELINE | 2 Participants |
| Arm A4 | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH < LLN, WITH FT3/FT4 TEST MISSING | 0 Participants |
| Arm A4 | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH > ULN, WITH TSH <= ULN AT BASELINE | 0 Participants |
| Arm A4 | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH < LLN | 0 Participants |
| Arm A4 | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH > ULN, WITH AT LEAST ONE FT3/FT4 TEST < LLN | 1 Participants |
| Arm A4 | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH < LLN, WITH ALL OTHER FT3/FT4 TEST <= ULN | 0 Participants |
| Arm A4 | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH > ULN, WITH ALL OTHER FT3/FT4 TEST >= LLN | 0 Participants |
| Arm A4 | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH > ULN | 3 Participants |
| Arm A4 | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH > ULN, WITH FT3/FT4 TEST MISSING | 2 Participants |
| Arm A4 | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH<LLN, LLN WITH AT LEAST ONE FT3/FT4 TEST>ULN | 0 Participants |
| Arm A4 | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH < LLN, WITH TSH >= LLN AT BASELINE | 0 Participants |
| Arm B4 | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH < LLN, WITH FT3/FT4 TEST MISSING | 0 Participants |
| Arm B4 | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH > ULN, WITH ALL OTHER FT3/FT4 TEST >= LLN | 0 Participants |
| Arm B4 | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH < LLN | 3 Participants |
| Arm B4 | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH < LLN, WITH ALL OTHER FT3/FT4 TEST <= ULN | 1 Participants |
| Arm B4 | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH > ULN, WITH TSH <= ULN AT BASELINE | 7 Participants |
| Arm B4 | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH < LLN, WITH TSH >= LLN AT BASELINE | 1 Participants |
| Arm B4 | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH > ULN | 7 Participants |
| Arm B4 | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH > ULN, WITH AT LEAST ONE FT3/FT4 TEST < LLN | 6 Participants |
| Arm B4 | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH > ULN, WITH FT3/FT4 TEST MISSING | 1 Participants |
| Arm B4 | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH<LLN, LLN WITH AT LEAST ONE FT3/FT4 TEST>ULN | 2 Participants |
| Arm A4 | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH > ULN, WITH ALL OTHER FT3/FT4 TEST >= LLN | 0 Participants |
| Arm A4 | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH > ULN | 2 Participants |
| Arm A4 | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH > ULN, WITH TSH <= ULN AT BASELINE | 1 Participants |
| Arm A4 | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH > ULN, WITH AT LEAST ONE FT3/FT4 TEST < LLN | 2 Participants |
| Arm A4 | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH > ULN, WITH FT3/FT4 TEST MISSING | 0 Participants |
| Arm A4 | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH < LLN | 0 Participants |
| Arm A4 | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH < LLN, WITH TSH >= LLN AT BASELINE | 0 Participants |
| Arm A4 | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH<LLN, LLN WITH AT LEAST ONE FT3/FT4 TEST>ULN | 0 Participants |
| Arm A4 | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH < LLN, WITH ALL OTHER FT3/FT4 TEST <= ULN | 0 Participants |
| Arm A4 | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH < LLN, WITH FT3/FT4 TEST MISSING | 0 Participants |
| Arm B4 | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH < LLN, WITH FT3/FT4 TEST MISSING | 0 Participants |
| Arm B4 | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH > ULN, WITH TSH <= ULN AT BASELINE | 3 Participants |
| Arm B4 | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH<LLN, LLN WITH AT LEAST ONE FT3/FT4 TEST>ULN | 0 Participants |
| Arm B4 | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH > ULN | 3 Participants |
| Arm B4 | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH < LLN, WITH TSH >= LLN AT BASELINE | 0 Participants |
| Arm B4 | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH < LLN | 0 Participants |
| Arm B4 | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH > ULN, WITH ALL OTHER FT3/FT4 TEST >= LLN | 0 Participants |
| Arm B4 | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH > ULN, WITH AT LEAST ONE FT3/FT4 TEST < LLN | 2 Participants |
| Arm B4 | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH < LLN, WITH ALL OTHER FT3/FT4 TEST <= ULN | 0 Participants |
| Arm B4 | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH > ULN, WITH FT3/FT4 TEST MISSING | 1 Participants |
| Arm A5 | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH < LLN | 0 Participants |
| Arm A5 | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH > ULN, WITH TSH <= ULN AT BASELINE | 1 Participants |
| Arm A5 | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH > ULN, WITH ALL OTHER FT3/FT4 TEST >= LLN | 1 Participants |
| Arm A5 | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH < LLN, WITH FT3/FT4 TEST MISSING | 0 Participants |
| Arm A5 | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH > ULN | 1 Participants |
| Arm A5 | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH > ULN, WITH FT3/FT4 TEST MISSING | 0 Participants |
| Arm A5 | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH<LLN, LLN WITH AT LEAST ONE FT3/FT4 TEST>ULN | 0 Participants |
| Arm A5 | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH > ULN, WITH AT LEAST ONE FT3/FT4 TEST < LLN | 0 Participants |
| Arm A5 | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH < LLN, WITH TSH >= LLN AT BASELINE | 0 Participants |
| Arm A5 | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH < LLN, WITH ALL OTHER FT3/FT4 TEST <= ULN | 0 Participants |
| Arm B5 | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH < LLN, WITH TSH >= LLN AT BASELINE | 1 Participants |
| Arm B5 | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH > ULN, WITH FT3/FT4 TEST MISSING | 0 Participants |
| Arm B5 | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH<LLN, LLN WITH AT LEAST ONE FT3/FT4 TEST>ULN | 0 Participants |
| Arm B5 | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH > ULN, WITH ALL OTHER FT3/FT4 TEST >= LLN | 3 Participants |
| Arm B5 | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH > ULN, WITH AT LEAST ONE FT3/FT4 TEST < LLN | 2 Participants |
| Arm B5 | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH < LLN, WITH ALL OTHER FT3/FT4 TEST <= ULN | 1 Participants |
| Arm B5 | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH > ULN, WITH TSH <= ULN AT BASELINE | 2 Participants |
| Arm B5 | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH > ULN | 5 Participants |
| Arm B5 | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH < LLN, WITH FT3/FT4 TEST MISSING | 0 Participants |
| Arm B5 | Number of Treated Participant With Laboratory Abnormalities - Thyroid | TSH < LLN | 1 Participants |
Overall Survival at 12 Months (OS12), Cohorts 1-4
Overall survival at 12 months (OS12) is defined as the percentage of participants who are alive at 12 months, measured as the survival rate at 12 months from Kaplan-Meier product limit cumulative probability.
Time frame: From first dose to up to 12 months after first dose
Population: All treated participants in Cohorts 1-4
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A1, Safety Lead-in | Overall Survival at 12 Months (OS12), Cohorts 1-4 | 47.3 Percentage of participants |
| Arms A2-A5, Safety Lead-in | Overall Survival at 12 Months (OS12), Cohorts 1-4 | 42.9 Percentage of participants |
| Arms B2-B5, Safety Lead-in | Overall Survival at 12 Months (OS12), Cohorts 1-4 | 37.5 Percentage of participants |
| Arm B3 | Overall Survival at 12 Months (OS12), Cohorts 1-4 | 32.8 Percentage of participants |
| Arm A4 | Overall Survival at 12 Months (OS12), Cohorts 1-4 | 38.9 Percentage of participants |
| Arm B4 | Overall Survival at 12 Months (OS12), Cohorts 1-4 | 86.7 Percentage of participants |
| Arm A4 | Overall Survival at 12 Months (OS12), Cohorts 1-4 | 41.7 Percentage of participants |
| Arm B4 | Overall Survival at 12 Months (OS12), Cohorts 1-4 | 44.4 Percentage of participants |
Overall Survival (OS), Cohorts 2-5
Overall survival (OS) is defined as the time between date of first dose and the date of death for Cohorts 2-5.
Time frame: From first dose to the date of death (up to approximately 55 months)
Population: All treated participants in Cohorts 2-5
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A1, Safety Lead-in | Overall Survival (OS), Cohorts 2-5 | 6.67 Months |
| Arms A2-A5, Safety Lead-in | Overall Survival (OS), Cohorts 2-5 | 6.47 Months |
| Arms B2-B5, Safety Lead-in | Overall Survival (OS), Cohorts 2-5 | 7.36 Months |
| Arm B3 | Overall Survival (OS), Cohorts 2-5 | 22.21 Months |
| Arm A4 | Overall Survival (OS), Cohorts 2-5 | 5.70 Months |
| Arm B4 | Overall Survival (OS), Cohorts 2-5 | 9.82 Months |
| Arm A4 | Overall Survival (OS), Cohorts 2-5 | 5.91 Months |
| Arm B4 | Overall Survival (OS), Cohorts 2-5 | 8.48 Months |
Progression-Free Survival at 6 Months (PFS6), Cohorts 2-5
Progression-free survival at 6 months (PFS6) is defined as the percentage of participants who are progression free and alive at 6 months following first dose date, measured as the survival rate at 6 months from Kaplan-Meier product limit cumulative probability of progression free. Progression is defined as: * ≥ 25% increase in sum of the products of perpendicular diameters of enhancing lesions compared with the smallest tumor measurement * Significant increase in T2 or fast fluid-attenuated inversion recovery (FLAIR) non-enhancing lesions on stable or increasing doses of corticosteroids * Any new lesion * Clear clinical deterioration not attributable to other causes apart from the tumor * Failure to return for evaluation as a result of death or deteriorating condition * Clear progression of non-measurable disease
Time frame: From first dose to up to 6 months after first dose
Population: All treated participants in Cohorts 2-5
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A1, Safety Lead-in | Progression-Free Survival at 6 Months (PFS6), Cohorts 2-5 | 9.4 Percentage of participants |
| Arms A2-A5, Safety Lead-in | Progression-Free Survival at 6 Months (PFS6), Cohorts 2-5 | 14.3 Percentage of participants |
| Arms B2-B5, Safety Lead-in | Progression-Free Survival at 6 Months (PFS6), Cohorts 2-5 | 0 Percentage of participants |
| Arm B3 | Progression-Free Survival at 6 Months (PFS6), Cohorts 2-5 | 20.0 Percentage of participants |
| Arm A4 | Progression-Free Survival at 6 Months (PFS6), Cohorts 2-5 | 20.0 Percentage of participants |
| Arm B4 | Progression-Free Survival at 6 Months (PFS6), Cohorts 2-5 | 11.4 Percentage of participants |
| Arm A4 | Progression-Free Survival at 6 Months (PFS6), Cohorts 2-5 | 5.3 Percentage of participants |
| Arm B4 | Progression-Free Survival at 6 Months (PFS6), Cohorts 2-5 | 14.0 Percentage of participants |
Progression-Free Survival (PFS), Cohort 1 Only
Progression-free survival (PFS) is defined as the time from first dose to the date of the first documented tumor progression or death due to any cause. Progression is defined as: * ≥ 25% increase in sum of the products of perpendicular diameters of enhancing lesions compared with the smallest tumor measurement * Significant increase in T2 or fast fluid-attenuated inversion recovery (FLAIR) non-enhancing lesions on stable or increasing doses of corticosteroids * Any new lesion * Clear clinical deterioration not attributable to other causes apart from the tumor * Failure to return for evaluation as a result of death or deteriorating condition * Clear progression of non-measurable disease
Time frame: From first dose to the date of the first documented tumor progression or death due to any cause (up to approximately 55 months)
Population: All treated participants in Cohort 1
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A1, Safety Lead-in | Progression-Free Survival (PFS), Cohort 1 Only | 6.21 Months |
| Arms A2-A5, Safety Lead-in | Progression-Free Survival (PFS), Cohort 1 Only | 4.53 Months |
Overall Survival (OS), Cohort 1 Only - Extended Collection
Overall survival (OS) is defined as the time between the date of diagnosis and the date of death in Cohort 1. Note: This outcome measure represents an updated version of the primary endpoint to include additional data collection that has occurred after the primary completion date. (Assessments were made until 17-Jan-2022).
Time frame: From first dose to the date of death (up to approximately 55 months)
Population: All treated participants in Cohort 1
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A1, Safety Lead-in | Overall Survival (OS), Cohort 1 Only - Extended Collection | 11.66 Months |
| Arms A2-A5, Safety Lead-in | Overall Survival (OS), Cohort 1 Only - Extended Collection | 10.78 Months |
Progression-Free Survival (PFS), Cohort 5 Only - Extended Collection
Progression-free survival (PFS) is defined as the time from first dose to the date of the first documented tumor progression or death due to any cause. Note: This outcome measure represents an updated version of the primary endpoint to include additional data collection that has occurred after the primary completion date. (Assessments were made until 17-Jan-2022). Progression is defined as: * ≥ 25% increase in sum of the products of perpendicular diameters of enhancing lesions compared with the smallest tumor measurement * Significant increase in T2 or fast fluid-attenuated inversion recovery (FLAIR) non-enhancing lesions on stable or increasing doses of corticosteroids * Any new lesion * Clear clinical deterioration not attributable to other causes apart from the tumor * Failure to return for evaluation as a result of death or deteriorating condition * Clear progression of non-measurable disease
Time frame: From first dose to the date of the first documented tumor progression or death due to any cause (up to approximately 55 months)
Population: All treated participants in Cohort 5
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A1, Safety Lead-in | Progression-Free Survival (PFS), Cohort 5 Only - Extended Collection | 1.22 Months |
| Arms A2-A5, Safety Lead-in | Progression-Free Survival (PFS), Cohort 5 Only - Extended Collection | 1.61 Months |
Progression-Free Survival (PFS), Cohorts 2-4 - Extended Collection
Progression-free survival (PFS) is defined as the time from first dose to the date of the first documented tumor progression or death due to any cause. Note: This outcome measure represents an updated version of the primary endpoint to include additional data collection that has occurred after the primary completion date. (Assessments were made until 17-Jan-2022). Progression is defined as: * ≥ 25% increase in sum of the products of perpendicular diameters of enhancing lesions compared with the smallest tumor measurement * Significant increase in T2 or fast fluid-attenuated inversion recovery (FLAIR) non-enhancing lesions on stable or increasing doses of corticosteroids * Any new lesion * Clear clinical deterioration not attributable to other causes apart from the tumor * Failure to return for evaluation as a result of death or deteriorating condition * Clear progression of non-measurable disease
Time frame: From first dose to the date of the first documented tumor progression or death due to any cause (up to approximately 55 months)
Population: All treated participants in Cohorts 2-4
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A1, Safety Lead-in | Progression-Free Survival (PFS), Cohorts 2-4 - Extended Collection | 1.74 Months |
| Arms A2-A5, Safety Lead-in | Progression-Free Survival (PFS), Cohorts 2-4 - Extended Collection | 1.38 Months |
| Arms B2-B5, Safety Lead-in | Progression-Free Survival (PFS), Cohorts 2-4 - Extended Collection | 1.38 Months |
| Arm B3 | Progression-Free Survival (PFS), Cohorts 2-4 - Extended Collection | 2.69 Months |
| Arm A4 | Progression-Free Survival (PFS), Cohorts 2-4 - Extended Collection | 1.41 Months |
| Arm B4 | Progression-Free Survival (PFS), Cohorts 2-4 - Extended Collection | 4.60 Months |