DLT was defined as any adverse event (AE) or abnormal laboratory value which were related to study treatment and assessed as unrelated to disease (disease progression), occurring during the first 21 days of treatment that met at least 1 of the study specified criteria. DLTs were graded according to the National Cancer Institute- Common Terminology Criteria for Adverse Events (NCI-CTCAE), version (v) 5.0.

The per protocol analysis set included all enrolled participants who had at least one dose of study treatment and either experienced DLT or did not have major treatment deviations during the DLT observation period.

An adverse event (AE) was any untoward medical occurrence in participant/ clinical study participant temporally associated with use of study intervention, whether/ not considered related to study intervention. TEAEs were defined as any AE that occurs during on-treatment period. The on-treatment period was defined as period that starts with first dose of study treatment and ends at last dose of study treatment +30 days, or start of new anti-cancer therapy [- 1 day], whichever occurred first. Serious TEAEs were any untoward medical occurrence at any dose that: suspected to cause death; life-threatening; required hospitalization; persistent/significant disability/incapacity and might caused congenital anomaly/birth defect. Serious treatment related TEAEs were related to study treatment and relatedness was judged by investigator. TEAEs were graded according to NCI-CTCAE v 5.0 (grade 3= severe, grade 4= life-threatening and grade 5= death related to AE). AEs included SAEs and all non-SAE.

The safety analysis set included all enrolled participants who received at least one dose of study intervention.

The following hematology laboratory parameters were assessed: activated partial thromboplastin time prolonged, anemia, hemoglobin increased, international normalized ratio (INR) increased, leukocytosis, lymphocyte count decreased, lymphocyte count increased, neutrophil count decreased, platelet count decreased and white blood cell decreased. Laboratory abnormality events were graded according to NCI CTCAE v5.0; grade 1=mild, grade 2=moderate, grade 3=severe, grade 4=life-threatening consequences and grade 5=death. In this outcome measure, those number of participants are reported who had hematology laboratory abnormality in any parameter of any CTCAE Grades.

The safety analysis set included all enrolled participants who received at least one dose of study intervention. Here "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure.

The following chemistry laboratory parameters were assessed: alanine aminotransferase increased, alkaline phosphatase increased, aspartate aminotransferase increased, blood bilirubin increased, creatine phosphokinase (CPK) increased, creatinine increased, hypercalcemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia and hyponatremia. Laboratory abnormality events were graded according to NCI CTCAE v5.0; grade 1=mild, grade 2=moderate, grade 3=severe, grade 4=life-threatening consequences and grade 5=death. In this outcome measure, those number of participants are reported who had chemistry laboratory abnormality in any parameter of any CTCAE Grades.

The safety analysis set included all enrolled participants who received at least one dose of study intervention. Here "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure.

Dose interruption was defined as a planned dosing day with 0 mg total dose administered. Dose interruptions were applicable to unexpected dose interruptions. In this outcome measure, dose interruptions for any drug were considered.

The safety analysis set included all enrolled participants who received at least one dose of study intervention.

A dose reduction was defined as the day when the actual dose was less than the planned dose at enrollment and the actual dose was greater than 0 mg (ie, missed doses were not counted as a reduction). In this outcome measure, dose reductions for any drug were considered.

The safety analysis set included all enrolled participants who received at least one dose of study intervention.

In this outcome measure, dose discontinuations for any drug due to TEAEs were considered.

The safety analysis set included all enrolled participants who received at least one dose of study intervention.

Extracranial response rate was defined as the percentage of participants with a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR) in extracranial lesions by Investigator assessment per RECIST v1.1. CR: disappearance of all target and non-target lesions. Any pathological lymph nodes (non-target) must have reduction in short axis to less than (<) 10 millimeter (mm). PR: at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Extracranial response evaluable set included all participants enrolled and received at least one dose of study treatment and had measurable tumor at baseline and at least one post baseline extracranial assessment.

Intracranial response rate as assessed using modified RECIST (mRECIST) v 1.1., was defined as the percentage of participants with brain or central nervous system (CNS) involvement who achieved a CR or PR. CR: disappearance of all target and non-target lesions. For target lesions: Any pathological lymph nodes must be <10 mm in the short axis. For non-target lesions: All lymph nodes identified as a site of disease at baseline must be non-pathological (eg, <10 mm short axis). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Intracranial response evaluable set included all participants enrolled and received at least one dose of study treatment and had measurable brain tumor at baseline and at least one post baseline intracranial assessment.

ORR: percentage of participants with BOR of confirmed CR/PR by investigator assessment in intracranial metastasis (mRECISTv1.1) and extracranial lesions (RECISTv1.1). RECIST v1.1- CR: disappearance of all target and non-target lesions. Any pathological lymph node (non-target) must have reduction in short axis to <10mm. PR: at least 30% decrease in sum of diameters of target lesions, taking as reference baseline sum diameters. mRECIST- CR: disappearance of all target and non-target lesion. For target lesion: Any pathological lymph nodes must be <10 mm in short axis. For non-target lesion: All lymph nodes identified as site of disease at baseline must be non-pathological (eg, <10 mm short axis). PR: at least 30% decrease in sum of diameters of target lesions, taking as reference baseline sum diameters.

The response evaluable population included all participants who received at least one dose of study treatment and had measurable disease at baseline and at least one post baseline disease assessment.

RANO response rate was defined as the percentage of glioblastoma participants who achieved a CR or PR per RANO. CR was defined as complete disappearance of all enhancing measurable and non-measurable disease sustained for more than or equal to (>=) 4 weeks; no new lesions; stable or improved non-enhancing (T2/ [fluid attenuated inversion recovery] FLAIR) lesions; off steroids and neurological condition stable or improved. PR was defined as >=50% decrease compared to baseline in the sum of the perpendicular diameters of all measurable enhancing lesions sustained for at least 4 weeks; no progression of non-measurable disease; no new lesions; stable or improved non enhancing (T2/FLAIR) lesions on the same or lower dose of corticosteroids compared with baseline scan; the corticosteroid dose at the time of the scan evaluation should be no greater than the dose at the time of the baseline scan and neurological condition stable or improved.

The response evaluable population analyzed. The outcome measure was to be evaluated only in glioblastoma participants; apart from Cohort 5 all other cohorts did not have any glioblastoma participants. Hence, "Overall Number of Participants Analyzed" for these cohorts is "0" and for Cohort 5 it signifies participants evaluable for this outcome.

The pharmacokinetic (PK) parameter analysis population included all enrolled participants treated who did not have protocol deviations influencing PK parameter assessment and have sufficient information to estimate at least 1 of the PK parameters of interest.

The PK parameter analysis population included all enrolled participants treated who did not have protocol deviations influencing PK parameter assessment, and have sufficient information to estimate at least 1 of the PK parameters of interest. Here "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure and contributed to data; 'Number Analyzed' signifies number of participants evaluable for the specified rows.

AUClast was determined using the linear/log trapezoidal method.

The PK parameter analysis population included all enrolled participants treated who did not have protocol deviations influencing PK parameter assessment, and have sufficient information to estimate at least 1 of the PK parameters of interest. Here "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure and contributed to data; 'Number Analyzed' signifies number of participants evaluable for the specified rows.

T1/2 was calculated as loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.

The PK parameter analysis population used. Here "Overall Number of Participants Analyzed"= participants evaluable for this outcome measure and contributed to data; 'Number Analyzed' =number of participants evaluable for specified rows. T1/2 could not be calculated for all participants due to challenges with determining T1/2 using an 8-hour profile particularly for C1D1 (where the pre-dose sample cannot be used), so the data could not be included and thus reported as 0 as applicable.

AUCinf was calculated as AUClast + (Clast/kel), where Clast is the predicted plasma concentration at the last quantifiable time point from the log-linear regression analysis. Those outcome measures are either due to either patient(s) has insufficient sample(s) (e.g., sampling only through Tmax or 1 sample after) for analyses or t1/2 could not be determined

PK parameter analysis population used. "Overall Number of Participants Analyzed"= participants evaluable for this outcome measure and contributed to data; 'Number Analyzed' =number of participants evaluable for specified rows. AUCinf could not be calculated either due to either participants had insufficient sample(s) (e.g., sampling only through Tmax or 1 sample after) for analyses or t1/2 could not be determined, which affects the ability to calculate AUCinf and thus reported 0 as applicable.

CL/F was calculated as Dose/AUCinf.

PK parameter analysis population used. "Overall Number of Participants Analyzed"= participants evaluable for this outcome measure and contributed to data; 'Number Analyzed' =number of participants evaluable for specified rows. CL/F could not be calculated either due to either participants had insufficient sample(s) (e.g., sampling only through Tmax or 1 sample after) for analyses or t1/2 could not be determined, which affects the ability to calculate CL/F and thus reported 0 as applicable.

Vz/F was calculated as Dose/(AUCinf * kel) where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.

PK parameter analysis population used. "Overall Number of Participants Analyzed"= participants evaluable for this outcome measure and contributed to data; 'Number Analyzed' =number of participants evaluable for specified rows. Vz/F could not be calculated either due to either participants had insufficient sample(s) (e.g., sampling only through Tmax or 1 sample after) for analyses or t1/2 could not be determined, which affects the ability to calculate Vz/F and thus reported 0 as applicable.

The PK parameter analysis population included all enrolled participants treated who did not have protocol deviations influencing PK parameter assessment, and have sufficient information to estimate at least 1 of the PK parameters of interest. Here "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure and contributed to data; 'Number Analyzed' signifies number of participants evaluable for the specified rows.

The PK parameter analysis population included all enrolled participants treated who did not have protocol deviations influencing PK parameter assessment, and have sufficient information to estimate at least 1 of the PK parameters of interest. Here "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure and contributed to data; 'Number Analyzed' signifies number of participants evaluable for the specified rows.

The PK parameter analysis population included all enrolled participants treated who did not have protocol deviations influencing PK parameter assessment, and have sufficient information to estimate at least 1 of the PK parameters of interest. Here "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure and contributed to data; 'Number Analyzed' signifies number of participants evaluable for the specified rows.

The PK parameter analysis population included all enrolled participants treated who did not have protocol deviations influencing PK parameter assessment, and have sufficient information to estimate at least 1 of the PK parameters of interest. Here "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure and contributed to data; 'Number Analyzed' signifies number of participants evaluable for the specified rows.

CL/F was calculated as Dose/AUCinf.

The PK parameter analysis population included all enrolled participants treated who did not have protocol deviations influencing PK parameter assessment, and have sufficient information to estimate at least 1 of the PK parameters of interest. Here "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure and contributed to data; 'Number Analyzed' signifies number of participants evaluable for the specified rows.

Vz/F was calculated as Dose/(AUCinf * kel) where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.

PK parameter analysis population used. "Overall Number of Participants Analyzed"= participants evaluable for this outcome measure and contributed to data; 'Number Analyzed' =number of participants evaluable for specified rows. Vz/F could not be calculated either due to either participants had insufficient sample(s) (e.g., sampling only through Tmax or 1 sample after) for analyses or t1/2 could not be determined, which affects the ability to calculate Vz/F and thus reported 0 as applicable.

T1/2 was calculated as loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. In the determination of the t1/2, steady-state was assumed and the pre-dose value was used for the 24-hour post-dose value, which could have enabled the reporting of the t1/2 value higher than 8 hours.

The PK parameter analysis population included all enrolled participants treated who did not have protocol deviations influencing PK parameter assessment, and have sufficient information to estimate at least 1 of the PK parameters of interest. Here "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure and contributed to data; 'Number Analyzed' signifies number of participants evaluable for the specified rows.

Rac was defined as area under the plasma concentration-time curve over the dosing interval at steady state (AUCss,τ) divided by area under the plasma concentration-time curve over the dosing interval from a single dose (AUCsd,τ).

The PK parameter analysis population included all enrolled participants treated who did not have protocol deviations influencing PK parameter assessment, and have sufficient information to estimate at least 1 of the PK parameters of interest. Here "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure and contributed to data; 'Number Analyzed' signifies number of participants evaluable for the specified rows.

Extracranial response rate was defined as the percentage of participants with a BOR of CR or confirmed PR in extracranial lesions by Investigator assessment per RECIST v1.1. CR: disappearance of all target and non-target lesions. Any pathological lymph nodes (non-target) must have reduction in short axis to < 10 mm. PR: at least a 30 % decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Extracranial response evaluable set included all participants enrolled and received at least one dose of study treatment and had measurable tumor at baseline and at least one post baseline extracranial assessment.

Intracranial response rate as assessed using modified mRECIST v 1.1., was defined as the percentage of participants with brain or CNS involvement who achieved a CR or PR. CR: disappearance of all target and non-target lesions. For target lesions: Any pathological lymph nodes must be <10 mm in the short axis. For non-target lesions: All lymph nodes identified as a site of disease at baseline must be non-pathological (eg, <10 mm short axis). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Intracranial response evaluable set included all participants enrolled and received at least one dose of study treatment and had measurable brain tumor at baseline and at least one post baseline intracranial assessment. Here "Overall Number of Participants Analyzed" as "0" signifies there was no participant evaluable in specified analysis set.

ORR: percentage of participants with BOR of confirmed CR/PR by investigator assessment in intracranial metastasis (mRECISTv1.1) and extracranial lesions (RECISTv1.1). RECIST v1.1- CR: disappearance of all target and non-target lesions. Any pathological lymph node (non-target) must have reduction in short axis to <10mm. PR: at least 30% decrease in sum of diameters of target lesions, taking as reference baseline sum diameters. mRECIST- CR: disappearance of all target and non-target lesion. For target lesion: Any pathological lymph nodes must be <10 mm in short axis. For non-target lesion: All lymph nodes identified as site of disease at baseline must be non-pathological (eg, <10 mm short axis). PR: at least 30% decrease in sum of diameters of target lesions, taking as reference baseline sum diameters.

The response evaluable population included all participants who received at least one dose of study treatment and had measurable disease at baseline and at least one post baseline disease assessment.

RANO response rate was defined as the percentage of glioblastoma participants who achieved a CR or PR per RANO. CR was defined as complete disappearance of all enhancing measurable and non-measurable disease sustained for >= 4 weeks; no new lesions; stable or improved non-enhancing (T2/FLAIR) lesions; off steroids and neurological condition stable or improved. PR was defined as >=50% decrease compared to baseline in the sum of the perpendicular diameters of all measurable enhancing lesions sustained for at least 4 weeks; no progression of non-measurable disease; stable or improved non enhancing (T2/FLAIR) lesions on the same or lower dose of corticosteroids compared with baseline scan; the corticosteroid dose at the time of the scan evaluation should be no greater than the dose at the time of the baseline scan and neurological condition stable or improved.

The response evaluable population included all participants who received at least one dose of study treatment and had measurable disease at baseline and at least one post baseline disease assessment. The outcome measure was to be evaluated only in glioblastoma participants. "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome and "0" represents no glioblastoma participants for respective reporting arms.

An AE was any untoward medical occurrence in participant/ clinical study participant temporally associated with use of study intervention, whether/ not considered related to study intervention. TEAEs were defined as any AE that occurs during on-treatment period. The on-treatment period was defined as period that starts with first dose of study treatment and ends at last dose of study treatment +30 days, or start of new anti-cancer therapy [- 1 day], whichever occurred first. Serious TEAEs were any untoward medical occurrence at any dose that: suspected to cause death; life-threatening; required hospitalization; persistent/significant disability/incapacity and might caused congenital anomaly/birth defect. Serious treatment related TEAEs were related to study treatment and relatedness was judged by investigator. TEAEs were graded according to NCI-CTCAE v 5.0 (grade 3= severe, grade 4= life-threatening and grade 5= death related to AE). AEs included SAEs and all non-SAE.

The safety analysis set included all enrolled participants who received at least one dose of study intervention.

The following hematology laboratory parameters were assessed: activated partial thromboplastin time prolonged, anemia, hemoglobin increased, INR increased, leukocytosis, lymphocyte count decreased, lymphocyte count increased, neutrophil count decreased, platelet count decreased and white blood cell decreased. Laboratory abnormality events were graded according to NCI CTCAE v5.0; grade 1=mild, grade 2=moderate, grade 3=severe, grade 4=life-threatening consequences and grade 5=death. In this outcome measure, those number of participants are reported who had hematology laboratory abnormality in any parameter of any CTCAE Grades.

The safety analysis set included all enrolled participants who received at least one dose of study intervention.

The following chemistry laboratory parameters were assessed: alanine aminotransferase increased, alkaline phosphatase increased, aspartate aminotransferase increased, blood bilirubin increased, CPK increased, creatinine increased, hypercalcemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia and hyponatremia. Laboratory abnormality events were graded according to NCI CTCAE v5.0; grade 1=mild, grade 2=moderate, grade 3=severe, grade 4=life-threatening consequences and grade 5=death. In this outcome measure, those number of participants are reported who had chemistry laboratory abnormality in any parameter of any CTCAE Grades.

The safety analysis set included all enrolled participants who received at least one dose of study intervention.

Dose interruption was defined as a planned dosing day with 0 mg total dose administered. Dose interruptions were applicable to unexpected dose interruptions. In this outcome measure, dose interruptions for any drug were considered.

The safety analysis set included all enrolled participants who received at least one dose of study intervention.

A dose reduction was defined as the day when the actual dose was less than the planned dose at enrollment and the actual dose was greater than 0 mg (ie, missed doses were not counted as a reduction). In this outcome measure, dose reductions for any drug were considered.

The safety analysis set included all enrolled participants who received at least one dose of study intervention.

In this outcome measure, dose discontinuations for any drug due to TEAEs were considered.

The safety analysis set included all enrolled participants who received at least one dose of study intervention.

TThe PK parameter analysis population included all enrolled participants treated who did not have protocol deviations influencing PK parameter assessment, and have sufficient information to estimate at least 1 of the PK parameters of interest. Here "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure and contributed to data; 'Number Analyzed' signifies number of participants evaluable for the specified rows.

The PK parameter analysis population included all enrolled participants treated who did not have protocol deviations influencing PK parameter assessment, and have sufficient information to estimate at least 1 of the PK parameters of interest. Here "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure and contributed to data; 'Number Analyzed' signifies number of participants evaluable for the specified rows.

AUClast was determined using the linear/log trapezoidal method.

The PK parameter analysis population included all enrolled participants treated who did not have protocol deviations influencing PK parameter assessment, and have sufficient information to estimate at least 1 of the PK parameters of interest. Here "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure and contributed to data; 'Number Analyzed' signifies number of participants evaluable for the specified rows.

The PK parameter analysis population included all enrolled participants treated who did not have protocol deviations influencing PK parameter assessment, and have sufficient information to estimate at least 1 of the PK parameters of interest. Here "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure and contributed to data; 'Number Analyzed' signifies number of participants evaluable for the specified rows.

The PK parameter analysis population included all enrolled participants treated who did not have protocol deviations influencing PK parameter assessment, and have sufficient information to estimate at least 1 of the PK parameters of interest. Here "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure and contributed to data; 'Number Analyzed' signifies number of participants evaluable for the specified rows.

The PK parameter analysis population included all enrolled participants treated who did not have protocol deviations influencing PK parameter assessment, and have sufficient information to estimate at least 1 of the PK parameters of interest. Here "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure and contributed to data; 'Number Analyzed' signifies number of participants evaluable for the specified rows.

The PK parameter analysis population included all enrolled participants treated who did not have protocol deviations influencing PK parameter assessment, and have sufficient information to estimate at least 1 of the PK parameters of interest. Here "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure and contributed to data; 'Number Analyzed' signifies number of participants evaluable for the specified rows.

CL/F was calculated as Dose/AUCinf.

The PK parameter analysis population included all enrolled participants treated who did not have protocol deviations influencing PK parameter assessment, and have sufficient information to estimate at least 1 of the PK parameters of interest. Here "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure and contributed to data; 'Number Analyzed' signifies number of participants evaluable for the specified rows.

DCR: percentage of participants with BOR of CR, PR/ SD, Non-CR/Non-PD by Investigator assessment. CR: disappearance of all target and non-target lesions. For target lesions: Any pathological lymph nodes must be <10 mm in short axis. For non-target lesions: All lymph nodes identified as site of disease at baseline must be non-pathological. PR: At least 30% decrease in sum of diameters of target lesions, taking as reference baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Progressive disease (PD). PD: for target lesions- At least 20% increase in sum of diameters of target lesions, taking as reference smallest sum of diameters recorded since treatment started. In addition, sum must have an absolute increase of at least 5 mm. PD for non-target lesions- unequivocal progression of existing non-target lesions. Non-CR/Non-PD: persistence of 1/ more non-target lesion(s) identified as site of disease.

Intracranial response evaluable set included all participants enrolled and received at least one dose of study treatment and had measurable brain tumor at baseline and at least one post baseline intracranial assessment.

DCR: percentage of participants with BOR of CR, PR or SD, Non-CR/Non-PD by Investigator assessment. CR: disappearance of all target & non-target lesions. For target lesions: Any pathological lymph nodes must be <10 mm in short axis. For non-target lesions: All lymph nodes identified as site of disease at baseline must be non-pathological. PR: At least 30% decrease in sum of diameters of target lesions, taking as reference baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. PD: for target lesions- At least 20% increase in sum of diameters of target lesions, taking as reference smallest sum of diameters recorded since treatment started. In addition, sum must have an absolute increase of at least 5 mm. PD for non-target lesions- unequivocal progression of existing non-target lesions. Non-CR/Non-PD: persistence of 1/ more non-target lesion(s) identified as site of disease.

The response evaluable population included all participants who received at least one dose of study treatment and had measurable disease at baseline and at least one post baseline disease assessment.

PFS was defined as the time from date of the first dose of study treatment to the earliest documented disease progression by Investigator assessment, or death due to any cause, whichever occurred first. PD: for target lesions- At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters recorded since the treatment started . In addition, the sum must have an absolute increase of at least 5 mm. PD for non-target lesions- unequivocal progression of existing non-target lesions. If a participant had not had a PFS event at the time of the analysis cutoff or at the start of any new anticancer therapy, PFS was censored at the date of last adequate tumor assessment. Analysis was performed using Kaplan-Meier method.

The safety analysis set included all enrolled participants who received at least one dose of study intervention.

PFS was defined as the time from date of the first dose of study treatment to the earliest documented disease progression by Investigator assessment, or death due to any cause, whichever occurred first. PD: for target lesions- at least 20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study (this includes baseline sum if that is smallest on study). In addition to the relative increase of 20%, sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered a sign of progression. PD for non-target lesions- unequivocal progression of existing non-target lesion. If a participant had not had a PFS event at the time of the analysis cutoff or at the start of any new anticancer therapy, PFS was censored at the date of last adequate tumor assessment. Overall PFS included evaluation for brain metastasis and extracranial lesions. Analysis was performed using Kaplan-Meier method.

The safety analysis set included all enrolled participants who received at least one dose of study intervention.

Overall survival was defined as the time from the date of first study treatment to the date of death due to any cause. Participants who were still alive at the end of the study or lost to follow-up were censored at the last date they were known to be alive. Analysis was performed using Kaplan-Meier method.

The full analysis set includes all enrolled participants.

DOR was defined as the time from date of the first radiographic response (CR or PR) to the earliest documented PD or death due to any cause. CR: disappearance of all target and non-target lesions. For target lesions: Any pathological lymph nodes must be <10 mm in the short axis. For non-target lesions: All lymph nodes identified as a site of disease at baseline must be non-pathological (eg, <10 mm short axis). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. PD: for target lesions- At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters recorded since the treatment started. In addition, the sum must have an absolute increase of at least 5 mm. PD for non-target lesions- unequivocal progression of existing non target lesions.

Intracranial response evaluable set included all participants enrolled and received at least one dose of study treatment and had measurable brain tumor at baseline and at least one post baseline intracranial assessment. Here "Overall Number of Participants Analyzed" as "0" signified participants did not have CR or PR.

DOR: time from date of first radiographic response (CR/PR) to earliest documented PD/ death due to any cause.CR: disappearance of all target and non-target lesions. Any pathological lymph nodes (non-target) must have reduction in short axis to < 10 mm. PR: at least a 30 % decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. PD: for target lesions- At least 20% increase in sum of diameters of target lesions, taking as reference smallest sum of diameters recorded since treatment started. PD for non-target lesions- unequivocal progression of existing non-target lesions.

The response evaluable population included all participants who received at least one dose of study treatment and had measurable disease at baseline and at least one post baseline disease assessment. Here "Overall Number of Participants Analyzed" signifies participants who have CR or PR and "0" signified participants did not have CR or PR for respective arms.

Time to response is the time from treatment start to date of first documentation of objective response (PR or CR). CR: disappearance of all target and non-target lesions. For target lesions: Any pathological lymph nodes must be <10 mm in the short axis. For non-target lesions: All lymph nodes identified as a site of disease at baseline must be non-pathological (eg, <10 mm short axis). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

Intracranial response evaluable set included all participants enrolled and received at least one dose of study treatment and had measurable brain tumor at baseline and at least one post baseline intracranial assessment.

Time to response is the time from treatment start to date of first documentation of objective response (PR or CR). CR: disappearance of all target and non-target lesions. Any pathological lymph nodes (non-target) must have reduction in short axis to < 10 mm. PR: at least a 30 % decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Response evaluable population.

The response evaluable population included all participants who received at least one dose of study treatment and had measurable disease at baseline and at least one post baseline disease assessment. Here "Overall Number of Participants Analyzed" signifies participants evaluable for this outcome measure.