Skip to main content
OpenTrials
Active, Not Recruiting

NCT Number: NCT03178552

A Study to Evaluate the Efficacy and Safety of Multiple Targeted Therapies as Treatments for Participants With Non-Small Cell Lung Cancer (NSCLC)

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.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

Notify Me

Key information

Conditions

Non-small Cell Lung Cancer Bronchial Neoplasms Carcinoma, Bronchogenic Carcinoma, Non-Small-Cell Lung Lung Diseases Lung Neoplasms Neoplasms Neoplasms by Site Respiratory Tract Diseases Respiratory Tract Neoplasms Thoracic Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2 / Phase 3

Primary location

Fundación CENIT para la Investigación en Neurociencias, Buenos Aires, Argentina

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Alectinib

Drug

Participants will receive 600 mg BID (Cohort A); 900, 1200, or 750 mg BID (Cohort B) or RP2D BID; orally until disease progression, unacceptable toxicity, withdrawal of consent or death.

Other names: RO5424802

Atezolizumab

Drug

Participants will receive atezolizumab 1200 mg IV infusion Q21D (Cohorts C and F) or 1680 mg IV infusion Q4W starting on Day 29 (Cohort E).

Other names: RO5541267

Pemetrexed

Drug

Participants will receive pemetrexed 500 mg/m^2 IV infusion on Day 1 Q21D.

Cisplatin

Drug

Participants will receive cisplatin 75 mg/m^2 IV on Day 1 Q21D.

carboplatin

Drug

Participants will receive carboplatin of AUC 5 or 6 IV on Day 1 Q21D.

Gemcitabine

Drug

Participants will receive gemcitabine 1000 or 1250 mg/m^2 on Days 1 and 8 of every cycle (1 Cycle=21 days).

Entrectinib

Drug

Participants will receive entrectinib 600 mg orally QD.

Other names: RO7102122

Cobimetinib

Drug

Participants will receive 60 mg PO QD on Days 1-21 of the initial run-in and triple-combination periods.

Other names: RO5514041

Vemurafenib

Drug

Participants will receive 960 mg PO BID on Days 1-21 of the initial run-in period, and 720 mg PO BID on Days 22-28 of the initial run-in period and on Days 1-28 of each cycle during the triple-combination period.

Other names: RO5185426

Bevacizumab

Drug

Participants will receive 15 mg/kg of IV bevacizumab on Day 1 of each 21-day cycle during the induction and maintenance periods.

Other names: RO4876646

Divarasib

Drug

Participants will receive divarasib PO QD until disease progression or unacceptable toxicity.

Other names: RO7435846; GDC-6036

docetaxel

Drug

Participants will receive IV docetaxel Q3W (75 mg/m^2) until disease progression or unacceptable toxicity

Primary outcomes

  1. 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

    Time frame: Baseline up to disease progression or death (up to approximately 6 years)

  2. Cohort B: Percentage of Participants with Confirmed Objective Response as Assessed by the Investigator Based on RECIST v1.1

    Time frame: Baseline up to disease progression or death (up to approximately 6 years)

  3. Cohort C: Progression Free Survival (PFS) as Assessed by the Investigator Based on RECIST v1.1 in bTMB PP1

    Time frame: Baseline up to disease progression or death (up to approximately 6 years)

  4. Cohort D: Percentage of Participants with Confirmed Objective Response as Assessed by the Investigator Based on RECIST v1.1

    Time frame: Baseline up to disease progression or death (up to approximately 6 years)

  5. Cohort E: Time in Response (TIR) as Assessed by the Investigator Based on RECIST v1.1

    Time frame: Month 12

  6. Cohort F: Investigator-Assessed Objective Response Rate (ORR) Based on RECIST v1.1

    Time frame: Baseline up to disease progression or death (up to approximately 6 years)

  7. Cohort G: Incidence of Adverse Events (AEs)

    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 outcomes

  1. Cohorts A-F: Duration of Response (DOR) as Assessed by the Investigator Based on RECIST v1.1

    Time frame: Baseline up to disease progression or death (up to approximately 6 years)

  2. Cohorts A, B and D: Percentage of Participants with Clinical Benefit Response as Assessed by the Investigator Based on RECIST v1.1

    Time frame: Baseline up to disease progression or death (up to approximately 6 years)

  3. Cohorts A, B, D, F: PFS as Assessed by the Investigator Based on RECIST v1.1

    Time frame: Baseline up to disease progression or death (up to approximately 6 years)

  4. Cohorts A-F: Duration of Response as Assessed by the Independent Review Facility (IRF) Based on RECIST v1.1

    Time frame: Baseline up to disease progression or death (up to approximately 6 years)

  5. Cohorts A, B and D: Percentage of Participants with Clinical Benefit Response as Assessed by IRF Based on RECIST v1.1

    Time frame: Baseline up to disease progression or death (up to approximately 6 years)

  6. Cohorts A-F: PFS as Assessed by IRF Based on RECIST v1.1

    Time frame: Baseline up to disease progression or death (up to approximately 6 years)

  7. Cohorts A-F: Percentage of Participants with Confirmed Objective Response as Assessed by IRF Based on RECIST v1.1

    Time frame: Baseline up to disease progression or death (up to approximately 6 years)

  8. Cohorts A-F: Overall Survival (OS)

    Time frame: Baseline up to approximately 6 years

  9. Cohorts A-F: Percentage of Participants with Adverse Events (AEs)

    Time frame: Baseline up to approximately 6 years

  10. 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)

    Time frame: Baseline, every 4 weeks through Cycle 6 (1 Cycle = 21 or 28 days), every 8 weeks thereafter up to approximately 6 years

  11. Cohorts A-F: Time to Deterioration in Patient-Reported Lung Cancer Symptoms (Cough, Dyspnea and Chest Pain) as Measured by the SILC Scale

    Time frame: Baseline, every 4 weeks through Cycle 6 (1 Cycle = 21 or 28 days), every 8 weeks thereafter up to approximately 6 years

  12. Cohorts C, E, F: Change from Baseline in Patient-Reported Lung Cancer Symptom (Cough, Dyspnea, Chest pain) Score as Measured by the SILC Scale

    Time frame: Baseline, every 4 weeks through Cycle 6 (1 Cycle = 21 or 28 days), every 8 weeks thereafter up to approximately 6 years

  13. 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)

    Time frame: Baseline, every 4 weeks through Cycle 6 (1 Cycle = 21 or 28 days), every 8 weeks thereafter up to approximately 6 years

  14. Cohorts A, B, D, E, F: Change from Baseline in HRQoL Scores as Measured by the SILC Scale

    Time frame: Baseline, every 4 weeks through Cycle 6 (1 Cycle = 21 or 28 days), every 8 weeks thereafter up to approximately 6 years

  15. Cohorts A-F: Change from Baseline in Patient Functioning and Symptoms Score as Measured by the EORTC QLQ-C30

    Time frame: Baseline, every 4 weeks through Cycle 6 (1 Cycle = 21 or 28 days), every 8 weeks thereafter up to approximately 6 years

  16. Cohorts A, B, D, E, F: Change from Baseline in Patient Functioning and Symptoms Score as Measured by the SILC Scale

    Time frame: Baseline, every 4 weeks through Cycle 6 (1 Cycle = 21 or 28 days), every 8 weeks thereafter up to approximately 6 years

  17. Cohorts A-F: Health Status Assessed as an Index Score Using the European Quality of Life 5-Dimension 5-Level (EQ-5D-5L) Questionnaire

    Time frame: Baseline, every 4 weeks through Cycle 6 (1 Cycle = 21 or 28 days), every 8 weeks thereafter up to approximately 6 years

  18. Cohort B: Percentage of Participants with Dose-Limiting Toxicities (DLTs)

    Time frame: Day 1 to Day 28 of Cycle 1 (cycle length = 28 days)

  19. Cohort B: Maximum Plasma Concentration (Cmax) of Alectinib

    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)

    DFP: Dose-Finding Phase; DEP: Dose-Expanding Phase.

  20. Cohort B: Area Under the Concentration-Time Curve from Time Zero to the Last Measurable Concentration (AUC0-last) of Alectinib

    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)

  21. Cohort B: Time to Reach Cmax (Tmax) of Alectinib

    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)

  22. Cohort B: Half-Life (t1/2) of Alectinib

    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)

  23. Cohort B: Metabolite to Parent Exposure Ratio for AUC0-last

    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)

  24. Cohort B: Metabolite to Parent Exposure Ratio for Cmax

    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)

  25. Cohort C: Percentage of Participants with Objective Response as Assessed by the Investigator Based on RECIST v1.1

    Time frame: Baseline up to disease progression or death (up to approximately 6 years)

  26. Cohort C: Percentage of Participants Free from Disease Progression as Assessed by the Investigator Based on RECIST v1.1 at Months 6 and 12

    Time frame: Months 6, 12

  27. Cohort C: PFS as Assessed by the Investigator based on RECIST v1.1 in bTMB PP2

    Time frame: Baseline up to disease progression or death (up to approximately 6 years)

  28. Cohort C: OS in bTMB PP2

    Time frame: Baseline up to approximately 6 years

  29. Cohort D: Time to CNS progression as Assessed by the Investigator Based on RECIST v1.1

    Time frame: Baseline up to CNS progression (up to approximately 6 years)

  30. Cohort D: Time to CNS progression as Assessed by the IRF Based on RECIST v1.1

    Time frame: Baseline up to CNS progression (up to approximately 6 years)

  31. 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

    Time frame: Baseline, every 4 weeks until disease progression, up to approximately 6 years

  32. 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

    Time frame: Baseline, every 4 weeks until disease progression, up to approximately 6 years

  33. Cohort D: Mean Plasma Concentration of Entrectinib

    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).

  34. Cohort D: Mean Plasma Concentration of Entrectinib Metabolite M5

    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).

  35. Cohort E: TIR as Assessed by the Investigator Based on RECIST v1.1

    Time frame: Month 9

  36. Cohort E: TIR as Assessed by IRF

    Time frame: Month 12

  37. Cohorts E, F: Serum Concentration of Atezolizumab

    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)

  38. Cohorts E, F: Change from Baseline in Anti-Drug Antibodies (ADAs)

    Time frame: Baseline up to approximately 6 years

  39. 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)

    Time frame: Baseline up to approximately 6 years

  40. 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

    Time frame: Baseline up to approximately 6 years

  41. Cohort G: Plasma Concentration of Divarasib

    Time frame: Baseline up to approximately 6 years

Sponsors and collaborators

Lead sponsor

Hoffmann-La Roche

Industry

Registry information

Official study 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)

Acronym: B-FAST

Important dates

Study start
2017
Primary completion
2026
Study completion
2026
First posted
Jun 7, 2017
Registry last updated
Jun 5, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.