Brief Summary
This is a phase 2/3, global, multicenter, open-label, multi-cohort study designed to evaluate the safety and efficacy of targeted therapies or immunotherapy as single agents or in combination in participants with unresectable, advanced or metastatic NSCLC determined to harbor oncogenic somatic mutations or positive by tumor mutational burden (TMB) assay as identified by a blood-based next-generation sequencing (NGS) circulating tumor DNA (ctDNA) assay.
Brief Title
A Study to Evaluate the Efficacy and Safety of Multiple Targeted Therapies as Treatments for Participants With Non-Small Cell Lung Cancer (NSCLC)
Categories
Completion Date
Completion Date Type
Estimated
Conditions
Non-Small Cell Lung Cancer
Eligibility Criteria
Inclusion Criteria:
* Histologically or cytologically confirmed diagnosis of unresectable Stage IIIb not amenable to treatment with combined modality chemoradiation (advanced) or Stage IV (metastatic) NSCLC
* Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
* Measurable disease
* Adequate recovery from most recent systemic or local treatment for cancer
* Adequate organ function
* Life expectancy greater than or equal to (\>/=) 12 weeks
* For female participants of childbearing potential and male participants, willingness to use acceptable methods of contraception
Exclusion Criteria:
* Inability to swallow oral medication
* Women who are pregnant or lactating
* Symptomatic, untreated CNS metastases
* History of malignancy other than NSCLC within 5 years prior to screening with the exception of malignancies with negligible risk of metastasis or death
* Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction, or cerebrovascular accident within 3 months prior to randomization, unstable arrhythmias, or unstable angina
* Known active or uncontrolled human immunodeficiency virus (HIV) infection
* Either a concurrent condition or history of a prior condition that places the patient at unacceptable risk if he/she were treated with the study drug or confounds the ability to interpret data from the study
* Inability to comply with other requirements of the protocol
* Histologically or cytologically confirmed diagnosis of unresectable Stage IIIb not amenable to treatment with combined modality chemoradiation (advanced) or Stage IV (metastatic) NSCLC
* Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
* Measurable disease
* Adequate recovery from most recent systemic or local treatment for cancer
* Adequate organ function
* Life expectancy greater than or equal to (\>/=) 12 weeks
* For female participants of childbearing potential and male participants, willingness to use acceptable methods of contraception
Exclusion Criteria:
* Inability to swallow oral medication
* Women who are pregnant or lactating
* Symptomatic, untreated CNS metastases
* History of malignancy other than NSCLC within 5 years prior to screening with the exception of malignancies with negligible risk of metastasis or death
* Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction, or cerebrovascular accident within 3 months prior to randomization, unstable arrhythmias, or unstable angina
* Known active or uncontrolled human immunodeficiency virus (HIV) infection
* Either a concurrent condition or history of a prior condition that places the patient at unacceptable risk if he/she were treated with the study drug or confounds the ability to interpret data from the study
* Inability to comply with other requirements of the protocol
Inclusion Criteria
Inclusion Criteria:
* Histologically or cytologically confirmed diagnosis of unresectable Stage IIIb not amenable to treatment with combined modality chemoradiation (advanced) or Stage IV (metastatic) NSCLC
* Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
* Measurable disease
* Adequate recovery from most recent systemic or local treatment for cancer
* Adequate organ function
* Life expectancy greater than or equal to (\>/=) 12 weeks
* For female participants of childbearing potential and male participants, willingness to use acceptable methods of contraception
* Histologically or cytologically confirmed diagnosis of unresectable Stage IIIb not amenable to treatment with combined modality chemoradiation (advanced) or Stage IV (metastatic) NSCLC
* Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
* Measurable disease
* Adequate recovery from most recent systemic or local treatment for cancer
* Adequate organ function
* Life expectancy greater than or equal to (\>/=) 12 weeks
* For female participants of childbearing potential and male participants, willingness to use acceptable methods of contraception
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT03178552
Org Class
Industry
Org Full Name
Hoffmann-La Roche
Org Study Id
BO29554
Overall Status
Active, not recruiting
Phases
Phase 2
Phase 3
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
A Phase II/III Multicenter Study Evaluating the Efficacy and Safety of Multiple Targeted Therapies as Treatments for Patients With Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) Harboring Actionable Somatic Mutations Detected in Blood (B-FAST: Blood-First Assay Screening Trial)
Primary Outcomes
Outcome Measure
Cohort A: Percentage of Participants with Confirmed Objective Response as Assessed by the Investigator Based on the Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1
Outcome Time Frame
Baseline up to disease progression or death (up to approximately 6 years)
Outcome Measure
Cohort B: Percentage of Participants with Confirmed Objective Response as Assessed by the Investigator Based on RECIST v1.1
Outcome Time Frame
Baseline up to disease progression or death (up to approximately 6 years)
Outcome Measure
Cohort C: Progression Free Survival (PFS) as Assessed by the Investigator Based on RECIST v1.1 in bTMB PP1
Outcome Time Frame
Baseline up to disease progression or death (up to approximately 6 years)
Outcome Measure
Cohort D: Percentage of Participants with Confirmed Objective Response as Assessed by the Investigator Based on RECIST v1.1
Outcome Time Frame
Baseline up to disease progression or death (up to approximately 6 years)
Outcome Measure
Cohort E: Time in Response (TIR) as Assessed by the Investigator Based on RECIST v1.1
Outcome Time Frame
Month 12
Outcome Measure
Cohort F: Investigator-Assessed Objective Response Rate (ORR) Based on RECIST v1.1
Outcome Time Frame
Baseline up to disease progression or death (up to approximately 6 years)
Outcome Measure
Cohort G: Incidence of Adverse Events (AEs)
Outcome Time Frame
Baseline to last dose of study treatment + 30 days or until initiation of new anticancer therapy, whichever occurs first (up to approximately 6 years)
Secondary Ids
Secondary Id
2017-000076-28
Secondary Outcomes
Outcome Time Frame
Baseline up to disease progression or death (up to approximately 6 years)
Outcome Measure
Cohorts A-F: Duration of Response (DOR) as Assessed by the Investigator Based on RECIST v1.1
Outcome Time Frame
Baseline up to disease progression or death (up to approximately 6 years)
Outcome Measure
Cohorts A, B and D: Percentage of Participants with Clinical Benefit Response as Assessed by the Investigator Based on RECIST v1.1
Outcome Time Frame
Baseline up to disease progression or death (up to approximately 6 years)
Outcome Measure
Cohorts A, B, D, F: PFS as Assessed by the Investigator Based on RECIST v1.1
Outcome Time Frame
Baseline up to disease progression or death (up to approximately 6 years)
Outcome Measure
Cohorts A-F: Duration of Response as Assessed by the Independent Review Facility (IRF) Based on RECIST v1.1
Outcome Time Frame
Baseline up to disease progression or death (up to approximately 6 years)
Outcome Measure
Cohorts A, B and D: Percentage of Participants with Clinical Benefit Response as Assessed by IRF Based on RECIST v1.1
Outcome Time Frame
Baseline up to disease progression or death (up to approximately 6 years)
Outcome Measure
Cohorts A-F: PFS as Assessed by IRF Based on RECIST v1.1
Outcome Time Frame
Baseline up to disease progression or death (up to approximately 6 years)
Outcome Measure
Cohorts A-F: Percentage of Participants with Confirmed Objective Response as Assessed by IRF Based on RECIST v1.1
Outcome Time Frame
Baseline up to approximately 6 years
Outcome Measure
Cohorts A-F: Overall Survival (OS)
Outcome Time Frame
Baseline up to approximately 6 years
Outcome Measure
Cohorts A-F: Percentage of Participants with Adverse Events (AEs)
Outcome Time Frame
Baseline, every 4 weeks through Cycle 6 (1 Cycle = 21 or 28 days), every 8 weeks thereafter up to approximately 6 years
Outcome Measure
Cohorts A, B, D, E, F: Percentage of Participants with Improvement Compared with Baseline in Total Severity Symptom Score as Measured by Symptoms in Lung Cancer (SILC) Scale in Patient-Reported Lung Cancer Symptoms (Cough, Dyspnea and Chest Pain)
Outcome Time Frame
Baseline, every 4 weeks through Cycle 6 (1 Cycle = 21 or 28 days), every 8 weeks thereafter up to approximately 6 years
Outcome Measure
Cohorts A-F: Time to Deterioration in Patient-Reported Lung Cancer Symptoms (Cough, Dyspnea and Chest Pain) as Measured by the SILC Scale
Outcome Time Frame
Baseline, every 4 weeks through Cycle 6 (1 Cycle = 21 or 28 days), every 8 weeks thereafter up to approximately 6 years
Outcome Measure
Cohorts C, E, F: Change from Baseline in Patient-Reported Lung Cancer Symptom (Cough, Dyspnea, Chest pain) Score as Measured by the SILC Scale
Outcome Time Frame
Baseline, every 4 weeks through Cycle 6 (1 Cycle = 21 or 28 days), every 8 weeks thereafter up to approximately 6 years
Outcome Measure
Cohorts A-F: Change from Baseline in Health Related Quality of Life (HRQoL) Scores as Measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - C30 (EORTC QLQ-C30)
Outcome Time Frame
Baseline, every 4 weeks through Cycle 6 (1 Cycle = 21 or 28 days), every 8 weeks thereafter up to approximately 6 years
Outcome Measure
Cohorts A, B, D, E, F: Change from Baseline in HRQoL Scores as Measured by the SILC Scale
Outcome Time Frame
Baseline, every 4 weeks through Cycle 6 (1 Cycle = 21 or 28 days), every 8 weeks thereafter up to approximately 6 years
Outcome Measure
Cohorts A-F: Change from Baseline in Patient Functioning and Symptoms Score as Measured by the EORTC QLQ-C30
Outcome Time Frame
Baseline, every 4 weeks through Cycle 6 (1 Cycle = 21 or 28 days), every 8 weeks thereafter up to approximately 6 years
Outcome Measure
Cohorts A, B, D, E, F: Change from Baseline in Patient Functioning and Symptoms Score as Measured by the SILC Scale
Outcome Time Frame
Baseline, every 4 weeks through Cycle 6 (1 Cycle = 21 or 28 days), every 8 weeks thereafter up to approximately 6 years
Outcome Measure
Cohorts A-F: Health Status Assessed as an Index Score Using the European Quality of Life 5-Dimension 5-Level (EQ-5D-5L) Questionnaire
Outcome Time Frame
Day 1 to Day 28 of Cycle 1 (cycle length = 28 days)
Outcome Measure
Cohort B: Percentage of Participants with Dose-Limiting Toxicities (DLTs)
Outcome Description
DFP: Dose-Finding Phase; DEP: Dose-Expanding Phase.
Outcome Time Frame
DFP: pre-dose (0 hours [hr]) on Day 1 of Cycle 2; 0.5, 1, 2, 4, 6, 8 and 10 hr post-dose on Day 1 of Cycle 2 (1 Cycle=28 days)
Outcome Measure
Cohort B: Maximum Plasma Concentration (Cmax) of Alectinib
Outcome Time Frame
DFP: pre-dose (0 hr) on Day 1 of Cycle 2; 0.5, 1, 2, 4, 6, 8 and 10 hr post-dose on Day 1 of Cycle 2 (1 Cycle=28 days)
Outcome Measure
Cohort B: Area Under the Concentration-Time Curve from Time Zero to the Last Measurable Concentration (AUC0-last) of Alectinib
Outcome Time Frame
DFP: pre-dose (0 hr) on Day 1 of Cycle 2; 0.5, 1, 2, 4, 6, 8 and 10 hr post-dose on Day 1 of Cycle 2 (1 Cycle=28 days)
Outcome Measure
Cohort B: Time to Reach Cmax (Tmax) of Alectinib
Outcome Time Frame
DFP: pre-dose (0 hr) on Day 1 of Cycle 2; 0.5, 1, 2, 4, 6, 8 and 10 hr post-dose on Day 1 of Cycle 2 (1 Cycle=28 days)
Outcome Measure
Cohort B: Half-Life (t1/2) of Alectinib
Outcome Time Frame
DFP: pre-dose (0 hr) on Day 1 of Cycle 2; 0.5, 1, 2, 4, 6, 8 and 10 hr post-dose on Day 1 of Cycle 2 (1 Cycle=28 days)
Outcome Measure
Cohort B: Metabolite to Parent Exposure Ratio for AUC0-last
Outcome Time Frame
DFP: pre-dose (0 hr) on Day 1 of Cycle 2; 0.5, 1, 2, 4, 6, 8 and 10 hr post-dose on Day 1 of Cycle 2 (1 Cycle=28 days)
Outcome Measure
Cohort B: Metabolite to Parent Exposure Ratio for Cmax
Outcome Time Frame
Baseline up to disease progression or death (up to approximately 6 years)
Outcome Measure
Cohort C: Percentage of Participants with Objective Response as Assessed by the Investigator Based on RECIST v1.1
Outcome Time Frame
Months 6, 12
Outcome Measure
Cohort C: Percentage of Participants Free from Disease Progression as Assessed by the Investigator Based on RECIST v1.1 at Months 6 and 12
Outcome Time Frame
Baseline up to disease progression or death (up to approximately 6 years)
Outcome Measure
Cohort C: PFS as Assessed by the Investigator based on RECIST v1.1 in bTMB PP2
Outcome Time Frame
Baseline up to approximately 6 years
Outcome Measure
Cohort C: OS in bTMB PP2
Outcome Time Frame
Baseline up to CNS progression (up to approximately 6 years)
Outcome Measure
Cohort D: Time to CNS progression as Assessed by the Investigator Based on RECIST v1.1
Outcome Time Frame
Baseline up to CNS progression (up to approximately 6 years)
Outcome Measure
Cohort D: Time to CNS progression as Assessed by the IRF Based on RECIST v1.1
Outcome Time Frame
Baseline, every 4 weeks until disease progression, up to approximately 6 years
Outcome Measure
Cohort D: Percentage of Participants who have shown improvement compared with Baseline in patient-reported cognitive function, fatigue, HRQoL, headache and vision disorder per the EORTC QLQ-C30
Outcome Time Frame
Baseline, every 4 weeks until disease progression, up to approximately 6 years
Outcome Measure
Cohort D: Percentage of Participants who have shown improvement compared with Baseline in patient-reported cognitive function, fatigue, HRQoL, headache and vision disorder per the EORTC QLQ-BN20
Outcome Time Frame
Pre-dose (0 hr), 1.5 and 4 hr post-dose on Day 1 of Cycles 1, 2, 3, 4 and 5; and pre-dose on Day 1 of each subsequent treatment cycle (1 cycle = 28 days).
Outcome Measure
Cohort D: Mean Plasma Concentration of Entrectinib
Outcome Time Frame
Pre-dose (0 hr), 1.5 and 4 hr post-dose on Day 1 of Cycles 1, 2, 3, 4 and 5; and pre-dose on Day 1 of each subsequent treatment cycle (1 cycle = 28 days).
Outcome Measure
Cohort D: Mean Plasma Concentration of Entrectinib Metabolite M5
Outcome Time Frame
Month 9
Outcome Measure
Cohort E: TIR as Assessed by the Investigator Based on RECIST v1.1
Outcome Time Frame
Month 12
Outcome Measure
Cohort E: TIR as Assessed by IRF
Outcome Time Frame
Pre-dose (0 hr), 1.5 and 4 hr post-dose on Day 1 of Cycles 1, 2, 3, 4 and 5; and pre-dose on Day 1 of each subsequent treatment cycle (1 cycle = 28 days)
Outcome Measure
Cohorts E, F: Serum Concentration of Atezolizumab
Outcome Time Frame
Baseline up to approximately 6 years
Outcome Measure
Cohorts E, F: Change from Baseline in Anti-Drug Antibodies (ADAs)
Outcome Time Frame
Baseline up to approximately 6 years
Outcome Measure
Cohorts E, F: Time to Confirmed Deterioration (TTCD) in Participant-Reported Lung Cancer Symptoms of Cough, Dyspnea, and Chest Pain, as Measured by the Symptoms in Lung Cancer (SILC)
Outcome Time Frame
Baseline up to approximately 6 years
Outcome Measure
Cohorts E, F: Proportion of Participants who Improve Compared with Baseline in Participant-Reported Lung Cancer Symptoms of Cough, Dyspnea, and Chest Pain, as Measured by the SILC
Outcome Time Frame
Baseline up to approximately 6 years
Outcome Measure
Cohort G: Plasma Concentration of Divarasib
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Haiying Cheng
Investigator Email
HCHENG@montefiore.org
Investigator Phone
718-405-8404