Advanced Solid Tumors
Conditions
Keywords
BMS-986466, KRAS G12C-mutant, Pancreatic duct adenocarcinoma, Biliary tract cancer, Colorectal cancer, Non-small cell lung cancer
Brief summary
The purpose of this study is to find a safe, tolerable, and efficacious dose of BMS-986466 when given orally, in combination with adagrasib with or without cetuximab in participants with advanced KRAS G12C-mutant non-small cell lung cancer (NSCLC), pancreatic duct adenocarcinoma (PDAC), biliary tract cancer (BTC), or colorectal cancer (CRC).
Interventions
DRUGBMS-986466
Specified dose on specified days
DRUGAdagrasib
Specified dose on specified days
DRUGCetuximab
Specified dose on specified days
Sponsors
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: Part 1: * Individuals with a confirmed diagnosis of advanced KRAS G12C mutant NSCLC, CRC, PDAC and BTC that has spread to other parts of the body and cannot be removed surgically, may or may not have received previous treatment with KRAS G12C inhibitors. * For NSCLC and CRC: Individuals must have a documented KRAS G12C mutation status from NYS or FDA approved/cleared or CE marked test or, when such result is not available, positive KRAS G12C mutation status should be confirmed by a central laboratory in blood sample collected at the time of screening. * For PDAC and BTC: Participants must have a documented KRAS G12Cmutation from NYS or FDA-approved/cleared, or CE-marked test and blood samples will be collected only for retrospective testing. * Are relapsed or refractory to available standard of care treatments. Part 2: * Individuals with a confirmed diagnosis of advanced KRAS G12C-mutant NSCLC (Part 2A) or CRC (Part 2B) that has spread to other parts of the body and cannot be removed surgically and have not received previous treatment with KRAS inhibitors. * Individuals must have a documented KRAS G12C mutation from FDA or NYS approved/ cleared or CE marked test or, when such result is not available, positive KRAS G12C mutation status should be confirmed by a central laboratory in blood sample and /or tumor samples collected at the time of screening or from archival biopsies (less than 1 year old). * Have failed or disease recurrence or are not able to tolerate after at least 1 pervious line of therapy. Key
Exclusion criteria
* Have tumors with known BARF V600X, PTPN11 or KRASQ61X mutations. * Have or any significant heart disease or condition. * Receiving any medications that are substrate of CYP3A4 or inducers and/ or inhibitors Note: Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Number of Participants With Dose Limiting Toxicity (DLTs) | Cycle 1 (Each cycle consist of 28 days) | A DLT was defined as: * Death not related to disease progression * Grade (Gr) 4 (Life-threatening) neurotoxicity * Gr 3 (Severe) neurotoxicity of greater than 7 days * Gr 3 neurotoxicity does not revert to baseline within 28 days of the start date of the Grade 3 event * Seizures of grade that do not resolve within 7 days * Gr 4 cytokine release syndrome (CRS) that does not resolve to less than or equal to Gr 3 within 3 days * Gr 3 CRS that does not resolve to less than or equal to Grade 2 within 7 days * Any increase in aspartate aminotransferase (AST) or ALT \\\> 3 Ã- ULN and concurrent increase in total bilirubin \\\> 2 Ã- ULN that is unrelated to CRS and has no other probable reason to explain the combination of increases * Any other Gr 3 or 4 event deemed unexpected by the Investigator and considered a DLT upon evaluation by the safety review committee |
| Part 1: Number of Participants With Adverse Events (AEs) | From first dose until 100 days after last dose (Up to approximately 5 months) | An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. |
| Part 1: Number of Participants With Serious Adverse Events (SAEs) | From first dose until 30 days after last dose (Up to approximately 3 months) | A 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 or permanent damage, is a congenital anomaly/birth defect, is an important medical event. |
| Part 1: Number of Participants With AEs Leading to Discontinuation | From first dose until 30 days after last dose (Up to approximately 3 months) | An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatmen |
| Part 1: Number of Participants Who Died | From first dose until 100 days after last dose (Up to approximately 5 months) | Death due to any cause was assessed. |
| Part 2 Objective Response Rate (ORR) Assessed by Blinded Independent Central Review (BICR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 | From randomization untill disease progression or death, whichever occurs first (up to approximately 5 months) | Objective Response Rate (ORR) is defined as the percentage of participants with a confirmed Best overall response of Complete Response (CR) or Partial Response (PR) by RECIST v1.1. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \\\< 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 2- Time to Response (TTR) | From randomization untill disease progression or death, whichever occurs first (up to approximately 5 months) | Time to response (TTR) is defined as the time, in months, from randomization to the first objective documentation of PR or better assessed per BICR. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. |
| Part 2- Number of Participants With Adverse Events (AEs) | From first dose until 100 days after last dose (Up to approximately 5 months) | An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. |
| Part 2- Number of Participants With Serious Adverse Events (SAEs) | From first dose until 100 days after last dose (Up to approximately 5 months) | A Serious Adverse Event (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 or permanent damage, is a congenital anomaly/birth defect, is an important medical event. |
| Part 1: Maximum Observed Plasma Concentration (Cmax) | Cycle 1 Day 1 (Each cycle consist of 28 days) | Blood samples were collected to assess adequate PK profiles. Participants were not enrolled in Part 1a, 1b. |
| Part 2- Number of Participants Who Died | From first dose until 100 days after last dose (Up to approximately 5 months) | Death due to any cause was assessed. |
| Part 1a and 1b - Changes From Baseline in Pharmacodynamic Biomarker | Baseline and Cycle 1 Day 1 (Each cycle consist of 28 days) | Blood samples were collected for assessing pharmacodynamic parameters. |
| Part 2- Number of Participants With AEs Leading to Discontinuation | From first dose until 100 days after last dose (Up to approximately 5 months) | An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. |
| Part 1: Time to Maximum Concentration (Tmax) | Cycle 1 Day 1 (Each cycle consist of 28 days) | Blood samples were collected to assess adequate PK profiles. Participants were not enrolled in Part 1a, 1b. |
| Part 1: Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC[0-T]) | Cycle 1 Day 1 (Each cycle consist of 28 days) | Blood samples were collected to assess adequate PK profiles. Participants were not enrolled in Part 1a, 1b. |
| Part 2-Progression-free Survival (PFS) Assessed by BICR as Per RECIST v1.1 | From randomization untill disease progression or death, whichever occurs first (up to approximately 5 months) | Progression-Free Survival then (PFS) is defined as the time between the date of randomization and the date of first documented disease progression, based on Investigator assessments (per RECIST v1.1), or death due to any cause, whichever occurs first Calculated using Kaplan-Meier estimates. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. |
| Part 2- Disease Control Rate (DCR) Assessed by BICR as Per RECIST v1.1 | From randomization untill disease progression or death, whichever occurs first (up to approximately 5 months) | Disease Control Rate (DCR) (as per Recists v1.1) is defined as the number of randomized participants who achieve a BOR of confirmed CR, confirmed PR, or stable disease (SD), based on BICR assessments divided by the number of all randomized participants. |
| Part 2- Duration of Response (DOR) Assessed by BICR as Per RECIST v1.1 | From randomization untill disease progression or death, whichever occurs first (up to approximately 5 months) | Duration of objective response (DoR) is defined as the time between the date of first confirmed response (CR or PR) to the date of the first documented tumor progression (per RECIST 1.1) per BICR assessment, or death due to any cause, whichever occurs first. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. |
Countries
Australia, Finland, France, Israel, United States
Participant flow
Pre-assignment details
Study was early terminated and participants were not enrolled in Part 1A and 1B (Dose Escalation) and Part 2A and 2B (Dose Expansion).
Participants by arm
| Arm | Count |
|---|---|
| Part 1: Drug-Drug Interaction (DDI) - BMS986466 10 MG + Adagrasib 400MG BID Participants with KRAS G12C-mutant Advanced Solid Tumors were treated with a single dose of BMS-986466 10 mg orally (PO) on Cycle 1 Day 1 and Day 9 and followed by regular administration from Cycle 3 Day 1 till study discontinuation. Participants were also administered with adagrasib 400 mg twice a day (BID) starting on Cycle 1 Day 4. | 5 |
| Total | 5 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Other Reasons | 1 |
| Overall Study | Study terminated by Sponsor | 4 |
Baseline characteristics
| Characteristic | Part 1: Drug-Drug Interaction (DDI) - BMS986466 10 MG + Adagrasib 400MG BID |
|---|---|
| Age, Continuous | 55.2 years STANDARD_DEVIATION 7.16 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race/Ethnicity, Customized BLACK OR AFRICAN AMERICAN | 1 Participants |
| Race/Ethnicity, Customized WHITE | 4 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 5 |
| other Total, other adverse events | 4 / 5 |
| serious Total, serious adverse events | 1 / 5 |
Outcome results
Primary
Part 1: Number of Participants Who Died
Death due to any cause was assessed.
Time frame: From first dose until 100 days after last dose (Up to approximately 5 months)
Population: All treated population include all participants who received at least 1 dose of study intervention. Participants were not enrolled in Part 1a, 1b. Prespecified to be collected for Part 1 only.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Drug-Drug Interaction (DDI) - BMS986466 10 MG + Adagrasib 400MG BID | Part 1: Number of Participants Who Died | 0 Participants |
Primary
Part 1: Number of Participants With Adverse Events (AEs)
An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment.
Time frame: From first dose until 100 days after last dose (Up to approximately 5 months)
Population: All treated population include all participants who received at least 1 dose of study intervention. Participants were not enrolled in Part 1a, 1b. Prespecified to be collected for Part 1 only
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Drug-Drug Interaction (DDI) - BMS986466 10 MG + Adagrasib 400MG BID | Part 1: Number of Participants With Adverse Events (AEs) | 4 Participants |
Primary
Part 1: Number of Participants With AEs Leading to Discontinuation
An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatmen
Time frame: From first dose until 30 days after last dose (Up to approximately 3 months)
Population: All treated population include all participants who received at least 1 dose of study intervention. Participants were not enrolled in Part 1a, 1b. Prespecified to be collected for Part 1 only.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Drug-Drug Interaction (DDI) - BMS986466 10 MG + Adagrasib 400MG BID | Part 1: Number of Participants With AEs Leading to Discontinuation | 0 Participants |
Primary
Part 1: Number of Participants With Dose Limiting Toxicity (DLTs)
A DLT was defined as: * Death not related to disease progression * Grade (Gr) 4 (Life-threatening) neurotoxicity * Gr 3 (Severe) neurotoxicity of greater than 7 days * Gr 3 neurotoxicity does not revert to baseline within 28 days of the start date of the Grade 3 event * Seizures of grade that do not resolve within 7 days * Gr 4 cytokine release syndrome (CRS) that does not resolve to less than or equal to Gr 3 within 3 days * Gr 3 CRS that does not resolve to less than or equal to Grade 2 within 7 days * Any increase in aspartate aminotransferase (AST) or ALT \\\> 3 Ã- ULN and concurrent increase in total bilirubin \\\> 2 Ã- ULN that is unrelated to CRS and has no other probable reason to explain the combination of increases * Any other Gr 3 or 4 event deemed unexpected by the Investigator and considered a DLT upon evaluation by the safety review committee
Time frame: Cycle 1 (Each cycle consist of 28 days)
Population: All treated participants were considered DLT evaluable if they complete ≥ 75% of all planned doses of BMS-986466 and adagrasib without experiencing a DLT or experience a DLT after receiving at least 1 dose of BMS-986466 and adagrasib. Participants were not enrolled in Part 1a, 1b. Prespecified to be collected for Part 1 only
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Drug-Drug Interaction (DDI) - BMS986466 10 MG + Adagrasib 400MG BID | Part 1: Number of Participants With Dose Limiting Toxicity (DLTs) | 0 Participants |
Primary
Part 1: Number of Participants With Serious Adverse Events (SAEs)
A 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 or permanent damage, is a congenital anomaly/birth defect, is an important medical event.
Time frame: From first dose until 30 days after last dose (Up to approximately 3 months)
Population: All treated population include all participants who received at least 1 dose of study intervention. Participants were not enrolled in Part 1a, 1b. Prespecified to be collected for Part 1 only
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Drug-Drug Interaction (DDI) - BMS986466 10 MG + Adagrasib 400MG BID | Part 1: Number of Participants With Serious Adverse Events (SAEs) | 1 Participants |
Primary
Part 2 Objective Response Rate (ORR) Assessed by Blinded Independent Central Review (BICR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Objective Response Rate (ORR) is defined as the percentage of participants with a confirmed Best overall response of Complete Response (CR) or Partial Response (PR) by RECIST v1.1. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \\\< 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: From randomization untill disease progression or death, whichever occurs first (up to approximately 5 months)
Population: All treated population include all participants who received at least 1 dose of study intervention. Participants were not enrolled in Part 2, hence participants analyzed is 0. Prespecified to be collected for Part 2 only
Secondary
Part 1a and 1b - Changes From Baseline in Pharmacodynamic Biomarker
Blood samples were collected for assessing pharmacodynamic parameters.
Time frame: Baseline and Cycle 1 Day 1 (Each cycle consist of 28 days)
Population: All treated participants with available biomarker data. Participants were not enrolled in Part 1a and 1b arm, hence participants analyzed is 0. Prespecified to be collected for Part 1A and 1B only.
Secondary
Part 1: Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC[0-T])
Blood samples were collected to assess adequate PK profiles. Participants were not enrolled in Part 1a, 1b.
Time frame: Cycle 1 Day 1 (Each cycle consist of 28 days)
Population: Pharmacokinetic (PK) evaluable population is a subset of PK participants (all participants who received at least 1 dose of BMS-986466 and/or adagrasib and had any available concentration-time data) which consist of all participants in the PK population with adequate PK profiles. Prespecified to be collected for Part 1 only.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Part 1: Drug-Drug Interaction (DDI) - BMS986466 10 MG + Adagrasib 400MG BID | Part 1: Area Under the Serum Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC[0-T]) | NA mcg*hr/mL |
Secondary
Part 1: Maximum Observed Plasma Concentration (Cmax)
Blood samples were collected to assess adequate PK profiles. Participants were not enrolled in Part 1a, 1b.
Time frame: Cycle 1 Day 1 (Each cycle consist of 28 days)
Population: Pharmacokinetic (PK) evaluable population is a subset of PK participants (all participants who received at least 1 dose of BMS-986466 and/or adagrasib and had any available concentration-time data) which consist of all participants in the PK population with adequate PK profiles. Prespecified to be collected for Part 1 only
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Part 1: Drug-Drug Interaction (DDI) - BMS986466 10 MG + Adagrasib 400MG BID | Part 1: Maximum Observed Plasma Concentration (Cmax) | NA ng/mL |
Secondary
Part 1: Time to Maximum Concentration (Tmax)
Blood samples were collected to assess adequate PK profiles. Participants were not enrolled in Part 1a, 1b.
Time frame: Cycle 1 Day 1 (Each cycle consist of 28 days)
Population: Pharmacokinetic (PK) evaluable population is a subset of PK participants (all participants who received at least 1 dose of BMS-986466 and/or adagrasib and had any available concentration-time data) which consist of all participants in the PK population with adequate PK profiles. Prespecified to be collected for Part 1 only
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Part 1: Drug-Drug Interaction (DDI) - BMS986466 10 MG + Adagrasib 400MG BID | Part 1: Time to Maximum Concentration (Tmax) | NA hours |
Secondary
Part 2- Disease Control Rate (DCR) Assessed by BICR as Per RECIST v1.1
Disease Control Rate (DCR) (as per Recists v1.1) is defined as the number of randomized participants who achieve a BOR of confirmed CR, confirmed PR, or stable disease (SD), based on BICR assessments divided by the number of all randomized participants.
Time frame: From randomization untill disease progression or death, whichever occurs first (up to approximately 5 months)
Population: Participants were not enrolled in Part 2 arm, hence participants analyzed is 0. Prespecified to be collected for Part 2 only
Secondary
Part 2- Duration of Response (DOR) Assessed by BICR as Per RECIST v1.1
Duration of objective response (DoR) is defined as the time between the date of first confirmed response (CR or PR) to the date of the first documented tumor progression (per RECIST 1.1) per BICR assessment, or death due to any cause, whichever occurs first. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Time frame: From randomization untill disease progression or death, whichever occurs first (up to approximately 5 months)
Population: Participants were not enrolled in Part 2 arm, hence participants analyzed is 0. Prespecified to be collected for Part 2 only
Secondary
Part 2- Number of Participants Who Died
Death due to any cause was assessed.
Time frame: From first dose until 100 days after last dose (Up to approximately 5 months)
Population: Participants were not enrolled in Part 2 arm, hence participants analyzed is 0. Prespecified to be collected for Part 2 only
Secondary
Part 2- Number of Participants With Adverse Events (AEs)
An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment.
Time frame: From first dose until 100 days after last dose (Up to approximately 5 months)
Population: Participants were not enrolled in Part 2 arm, hence participants analyzed is 0. Prespecified to be collected for Part 2 only
Secondary
Part 2- Number of Participants With AEs Leading to Discontinuation
An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment.
Time frame: From first dose until 100 days after last dose (Up to approximately 5 months)
Population: Participants were not enrolled in Part 2 arm, hence participants analyzed is 0. Prespecified to be collected for Part 2 only
Secondary
Part 2- Number of Participants With Serious Adverse Events (SAEs)
A Serious Adverse Event (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 or permanent damage, is a congenital anomaly/birth defect, is an important medical event.
Time frame: From first dose until 100 days after last dose (Up to approximately 5 months)
Population: Participants were not enrolled in Part 2 arm, hence participants analyzed is 0. Prespecified to be collected for Part 2 only
Secondary
Part 2-Progression-free Survival (PFS) Assessed by BICR as Per RECIST v1.1
Progression-Free Survival then (PFS) is defined as the time between the date of randomization and the date of first documented disease progression, based on Investigator assessments (per RECIST v1.1), or death due to any cause, whichever occurs first Calculated using Kaplan-Meier estimates. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Time frame: From randomization untill disease progression or death, whichever occurs first (up to approximately 5 months)
Population: Participants were not enrolled in Part 2 arm, hence participants analyzed is 0. Prespecified to be collected for Part 2 only
Secondary
Part 2- Time to Response (TTR)
Time to response (TTR) is defined as the time, in months, from randomization to the first objective documentation of PR or better assessed per BICR. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm.
Time frame: From randomization untill disease progression or death, whichever occurs first (up to approximately 5 months)
Population: Participants were not enrolled in Part 2 arm, hence participants analyzed is 0. Prespecified to be collected for Part 2 only