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

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)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: Alectinib; Drug: Atezolizumab; Drug: Pemetrexed; Drug: Cisplatin; Drug: Carboplatin; Drug: Gemcitabine; Drug: Entrectinib; Drug: Cobimetinib; Drug: Vemurafenib; Drug: Bevacizumab; Drug: Docetaxel; Drug: Divarasib

• Study Type: Interventional
• Enrollment (Estimated): 1000
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1125ABD
    • Fundación Cenit para la Investigación en Neurociencias
  • Buenos Aires, Argentina, C1181ACH
    • Hospital Italiano
  • Ciudad Autonoma Buenos Aires, Argentina, C1284AEB
    • Hospital Británico de Buenos Aires
• Australia
  • New South Wales
    • St Leonards, New South Wales, Australia, 2065
      • Royal North Shore Hospital
  • Queensland
    • Chermside, Queensland, Australia, 4032
      • The Prince Charles Hospital
  • South Australia
    • Kurralta Park, South Australia, Australia, 5037
      • Ashford Cancer Center Research
• Belgium
  • Brussels, Belgium, 1090
    • UZ Brussel
  • Brussels, Belgium, 1200
    • Cliniques Universitaires St-Luc
  • Leuven, Belgium, 3000
    • UZ Leuven Gasthuisberg
• Brazil
  • Rio de Janeiro, Brazil, 20560-120
    • Instituto Nacional de Câncer - INCA
  • Rio Grande do Sul
    • Ijuí, Rio Grande do Sul, Brazil, 98700-000
      • ONCOSITE - Centro de Pesquisa Clinica em Oncologia LTDA
    • Porto Alegre, Rio Grande do Sul, Brazil, 90610-000
      • Hospital Sao Lucas - PUCRS
  • São Paulo
    • São Paulo, São Paulo, Brazil, 01246-000
      • Instituto do Cancer do Estado de Sao Paulo - ICESP
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 0V9
      • CancerCare Manitoba
  • Ontario
    • Barrie, Ontario, Canada, L4M 6M2
      • Royal Victoria Regional Health Centre
    • Brampton, Ontario, Canada, L6R 3J7
      • William Osler Health System Brampton Civic Hospital
    • London, Ontario, Canada, N6A 5W9
      • London Health Sciences Centre · Victoria Hospital
    • Oshawa, Ontario, Canada, L1G 2B9
      • Lakeridge Health Center
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Health Sciences Centre
    • Toronto, Ontario, Canada, M5G 1Z5
      • Princess Margaret Cancer Center
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Jewish General Hospital
    • Québec, Quebec, Canada, G1V 4G5
      • IUCPQ (Hôpital Laval)
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, SK S7N 4H4
      • Saskatoon Cancer Centre
• Chile
  • Recoleta, Chile, 8420383
    • Bradford Hill Centro de Investigaciones Clinicas
• China
  • Beijing, China, 100142
    • Beijing Cancer Hospital
  • Changchun, China, 132013
    • Jilin Cancer Hospital
  • Changsha, China, 410013
    • Hunan Cancer Hospital
  • Changsha, China, 410100
    • The Second Xiangya Hospital Of Central South University
  • Chengdu, China, 610041
    • Sichuan Cancer Hospital
  • Chengdu, China, 610047
    • West China Hospital - Sichuan University
  • Guangzhou, China, 510120
    • The First Affiliated Hospital of Guangzhou Medical University Pharmacy
  • Hangzhou, China, 310022
    • Zhejiang Cancer Hospital
  • Jinan, China, 250117
    • Shandong Cancer Hospital
  • Nanchang, China, 330006
    • The Second Affiliated Hospital to Nanchang University
  • Nanjing, China, 210008
    • Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School
  • Shanghai, China, 200032
    • Fudan Unviversity Shanghai Cancer Center
  • Xi'an, China, 710061
    • First Affiliated Hospital of Medical College of Xi'an Jiaotong University
• France
  • Bordeaux, France, 33000
    • Institut Bergonie CLCC Bordeaux
  • Caen, France, 14076
    • Centre Francois Baclesse
  • Lille, France, 59020
    • Centre Oscar Lambret
  • Lyon, France, 69373
    • Centre Leon Berard
  • Nouilly, France, 57645
    • Hopital Robert Schuman
  • Nîmes, France, 30029
    • Hopital Caremeau
  • Paris, France, 75970
    • Hôpital Tenon
  • Paris, France, 75908
    • Hôpital Europeen Georges Pompidou
  • Poitiers, France, 86021
    • CHU Poitiers
  • Rennes, France, 35033
    • Hôpital Pontchaillou
  • Toulouse, France, 31059
    • CHU de Toulouse - Hopital Larrey
• Germany
  • Chemnitz, Germany, 09116
    • Klinikum Chemnitz Ggmbh
  • Gauting, Germany, 82131
    • Asklepios-Fachklinik Muenchen-Gauting
  • Heidelberg, Germany, 69126
    • Thoraxklinik Heidelberg gGmbH
  • Wiesbaden, Germany, 65199
    • HSK Dr.-Horst-Schmidt-Kliniken Klinik für Innere Medizin III Onkologie Hämatologie und Palliativmed
• Hong Kong
  • Hong Kong, Hong Kong
    • Queen Mary Hospital
  • Shatin, Hong Kong
    • Prince of Wales Hosp
• Israel
  • Beersheba, Israel, 8410101
    • Soroka Medical Center
  • Haifa, Israel, 3109601
    • Rambam Health Care Campus
  • Kfar Saba, Israel, 4428164
    • Meir Medical Center
  • Petah Tikva, Israel, 4941492
    • Rabin MC
  • Ramat Gan, Israel, 5262100
    • Chaim Sheba Medical Center
  • Tel Aviv, Israel, 6423906
    • Sourasky / Ichilov Hospital; Dept. of Oncology
• Italy
  • Campania
    • Napoli, Campania, Italy, 80131
      • Istituto Nazionale per lo Studio e la Cura dei Tumori Fondazione G. Pascale
  • Emilia-Romagna
    • Meldola, Emilia-Romagna, Italy, 47014
      • IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola
  • Friuli Venezia Giulia
    • Aviano, Friuli Venezia Giulia, Italy, 33081
      • Irccs Centro Di Riferimento Oncologico (CRO)
  • Lazio
    • Rome, Lazio, Italy, 00151
      • Azienda Ospedaliera San Camillo Forlanini
  • Lombardy
    • Bergamo, Lombardy, Italy, 24128
      • Asst Papa Giovanni Xxiii
    • Cremona, Lombardy, Italy, 26100
      • ASST di Cremona - Azienda Socio Sanitaria Territoriale di Cremona
    • Milan, Lombardy, Italy, 20141
      • Irccs Istituto Europeo Di Oncologia (IEO)
    • Monza, Lombardy, Italy, 20900
      • Asst Di Monza
  • Piedmont
    • Orbassano (TO), Piedmont, Italy, 10043
      • Azienda Sanitaria Ospedaliera S Luigi Gonzaga
• Japan
  • Bunkyō City, Japan, 113-8677
    • Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital
  • Fukuoka, Japan, 810-8563
    • National Hospital Organization Kyushu Medical Center
  • Fukuoka, Japan, 811-1395
    • National Hospital Organization Kyushu Cancer Center
  • Fukuoka, Japan, 812-8582
    • Kyushu University Hospital
  • Hiroshima, Japan, 734-8551
    • Hiroshima University Hospital
  • Ishikawa, Japan, 920-8641
    • Kanazawa University Hospital
  • Kanagawa, Japan, 241-8515
    • Kanagawa Cancer Center
  • Kyoto, Japan, 602-8566
    • University Hospital Kyoto Prefectural University of Medicine
  • Matsuyama, Japan, 791-0280
    • Shikoku Cancer Center
  • Miyagi, Japan, 980-8574
    • Tohoku University Hospital
  • Miyagi, Japan, 981-0914
    • Sendai Kousei Hospital
  • Niigata, Japan, 951-8520
    • Niigata University Medical & Dental Hospital
  • Niigata, Japan, 951-8566
    • Niigata Cancer Center Hospital
  • Osaka, Japan, 589-8511
    • Kindai University Hospital
  • Saga, Japan, 849-8501
    • Saga University Hospital
  • Shizuoka, Japan, 411-8777
    • Shizuoka Cancer Center
  • Tokyo, Japan, 135-8550
    • The Cancer Institute Hospital Of JFCR
  • Tokyo, Japan, 113-8431
    • Juntendo University Hospital
  • Tokyo, Japan, 181-8611
    • Kyorin University Hospital
  • Toyoake-shi, Japan, 470-1192
    • Fujita Health University Hospital
  • Wakayama, Japan, 641-8510
    • Wakayama Medical University Hospital
  • Yamaguchi, Japan, 775-0241
    • National Hospital Organization Yamaguchi - Ube Medical Center
• Mexico
  • Estado de Baja California
    • Tijuana, Estado de Baja California, Mexico, 22010
      • Hospital Angeles Tijuana
  • Mexico CITY (federal District)
    • Mexico City, Mexico CITY (federal District), Mexico, 03100
      • Health Pharma Professional Research
  • Nuevo León
    • Monterrey, Nuevo León, Mexico, 64710
      • AVIX Investigación Clínica S.C
  • San Luis Potosí
    • San Luis Potosí City, San Luis Potosí, Mexico, 78250
      • Oncológico Potosino
• New Zealand
  • Auckland, New Zealand, 1023
    • Auckland City Hospital
• Panama
  • Panama City, Panama, 0801
    • Hemato Oncología de Panamá Especializada
• Peru
  • Lima, Peru, 11
    • Hospital Nacional Edgardo Rebagliati Martins
  • Lima, Peru, 15038
    • Instituto Nacional de Enfermedades Neoplasicas
  • Lima, Peru
    • Instituto Peruano de Oncologia y Radioterapia
  • San Isidro, Peru, Lima 27
    • Clinica Ricardo Palma
• Poland
  • Gda?sk, Poland, 80-214
    • Uniwersyteckie Centrum Kliniczne, Klinika Onkologii i Radioterapii
  • Krakow, Poland, 31-202
    • Krakowski Szpital Specjalistyczny im sw.Jana Pawla II
  • Olsztyn, Poland, 10-357
    • Warminsko-Mazurskie Centrum Chorób P?uc w Olsztynie
  • Otwock, Poland, 05-400
    • Mazowieckie Centrum Leczenia Chorob Pluc I Gruzlicy
  • Poznan, Poland, 60-569
    • Wielkopolskie Centrum Pulmonologii i Torakochirurgii w Poznaniu
  • Warsaw, Poland, 02-781
    • Centrum Onkologii Instytut im.Marii Sklodowskiej-Curie
• Russia
  • Omsk, Russia, 644013
    • Clinical Oncology Dispensary
  • Moscow Oblast
    • Moscovskaya Oblast, Moscow Oblast, Russia, 143423
      • Moscow City Oncology Hospital #62
    • Moscow, Moscow Oblast, Russia, 105229
      • Principal Military Clinical Hospital n.a. N.N. Burdenko
  • Sankt-Peterburg
    • Saint Petersburg, Sankt-Peterburg, Russia, 197758
      • S-Pb clinical scientific practical center of specialized kinds of medical care (oncological)
• Serbia
  • Belgrade, Serbia, 11000
    • Clinical Center of Serbia
  • Belgrade, Serbia, 11080
    • University Hospital Medical Center Bezanijska kosa
  • Kamenitz, Serbia, 21204
    • Institute for pulmonary diseases of Vojvodina
  • Niš, Serbia, 18000
    • Clinical Center Nis
• Singapore
  • Singapore, Singapore, 169610
    • National Cancer Centre
  • Singapore, Singapore, 119228
    • National University Hospital
• South Korea
  • Gyeonggi-do, South Korea, 10408
    • National Cancer Center
  • Jeollanam-do, South Korea, 58128
    • Chonnam National University Hwasun Hospital
  • Seoul, South Korea, 03080
    • Seoul National University Hospital
  • Seoul, South Korea, 05505
    • Asan Medical Center
  • Seoul, South Korea, 120-752
    • Yonsei University Health System/Severance Hospital
• Spain
  • Alicante, Spain, 03010
    • Hospital General Univ. de Alicante
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Barcelona, Spain, 08036
    • Hospital Clinic I Provincial
  • Barcelona, Spain, 08916
    • ICO Badalona - Hospital Germans Trias I Pujol
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28034
    • Hospital Ramon y Cajal
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañón
  • Madrid, Spain, 28050
    • Centro Integral Oncologico Clara Campal
  • Madrid, Spain, 28222
    • Hospital Universitario Puerta de Hierro
  • Madrid, Spain, 28223
    • Hospital Quiron de Madrid
  • Málaga, Spain, 29010
    • Hospital Regional Universitario Carlos Haya
  • Seville, Spain, 41013
    • Hospital Universitario Virgen del Rocio
  • Valencia, Spain, 46010
    • Hospital Clinico Universitario de Valencia
  • Barcelona
    • L'Hospitalet de Llobregat, Barcelona, Spain, 08908
      • Insititut Catala D'Oncologia
  • LA Coruna
    • Santiago de Compostela, LA Coruna, Spain, 15706
      • Complejo Hospitalario Universitario de Santiago (CHUS)
  • Navarre
    • Pamplona, Navarre, Spain, 31008
      • Clinica Universitaria de Navarra
• Taiwan
  • Kaohsiung City, Taiwan, 83301
    • Kaohsiung Chang Gung Memorial Hospital
  • Taipei, Taiwan, 112
    • Taipei Veterans General Hospital
  • Taipei, Taiwan, 100
    • National Taiwan Uni Hospital
  • Taoyuan District, Taiwan, 333
    • Chang Gung Medical Foundation - Linkou
• Thailand
  • Bangkok, Thailand, 10700
    • Faculty of Med. Siriraj Hosp.
  • Hat Yai, Thailand, 90110
    • Prince of Songkla University
• Turkey (Türkiye)
  • Adana, Turkey (Türkiye), 01230
    • Baskent University Adana Dr. Turgut Noyan Practice and Research Hospital; Medical Oncology
  • Antalya, Turkey (Türkiye), 07070
    • Akdeniz University Medical Faculty; Medical Oncology Department
  • Edirne, Turkey (Türkiye), 22770
    • Trakya University Medical Faculty Research And Practice Hospital Medical Oncology Department
  • Istanbul, Turkey (Türkiye), 34214
    • Medipol University Medical Faculty; Oncology Department
  • Istanbul, Turkey (Türkiye), 34890
    • Marmara University Pendik Training and Research Hospital; Medikal Onkoloji
  • Kar??yaka, Turkey (Türkiye), 35575
    • Medikal Park Izmir Hospital
  • Sihhiye/Ankara, Turkey (Türkiye), 06230
    • Hacettepe Uni Medical Faculty Hospital; Oncology Dept
• United States
  • California
    • Sacramento, California, United States, 95817
      • UC Davis
  • Colorado
    • Denver, Colorado, United States, 80218
      • Rocky Mountain Cancer Center
  • Florida
    • Fort Myers, Florida, United States, 33901
      • SCRI Florida Cancer Specialists South
    • St. Petersburg, Florida, United States, 33705
      • Florida Cancer Specialist, North Region
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky
  • Nevada
    • Las Vegas, Nevada, United States, 89128
      • Comprehensive Cancer Centers of Nevada
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth Hitchcock Medical Center
  • New York
    • New York, New York, United States, 10021
      • Weill Cornell Medical College-New York Presbyterian Hospital
    • The Bronx, New York, United States, 10461
      • Montefiore Medical Center
  • Oregon
    • Portland, Oregon, United States, 97210
      • Oregon HSU
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States, 18015
      • St. Luke's University Health Network
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Sarah Cannon Research Institute / Tennessee Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

11

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A: Alectinib 600 Milligrams (mg); This cohort includes participants with anaplastic lymphoma kinase (ALK) positive NSCLC. Participants will receive alectinib 600 mg orally twice in a day (BID) until disease progression, unacceptable toxicity, withdrawal of consent or death. Enrollment to Cohort A is complete.	Drug: Alectinib; 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
Experimental: Cohort B: Dose Finding Phase (DFP) Alectinib; This cohort includes participants with rearranged during transfection (RET) positive NSCLC. Participants may receive alectinib 900 or 1200 mg orally BID until disease progression, unacceptable toxicity, withdrawal of consent or death if the recommended phase 2 dose (RP2D) is not established in any other clinical study. Participants may receive 750 mg or 600 mg, if it is unsafe to pursue the higher starting dose. Enrollment to Cohort B is complete.	Drug: Alectinib; 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
Experimental: Cohort B: Dose Expansion Phase (DEP) Alectinib; This cohort includes participants with RET positive NSCLC. Participants will receive alectinib at the RP2D established in the DFP of Cohort B or a separate clinical study. Participants will continue receiving study treatment until disease progression, unacceptable toxicity, withdrawal of consent or death. Enrollment to Cohort B is complete.	Drug: Alectinib; 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
Experimental: Cohort C: Atezolizumab 1200 mg; This cohort includes participants with bTMB positive NSCLC. Participants will receive atezolizumab at a dose of 1200 mg administered by IV infusion every 21 days (Q21D) until disease progression, loss of clinical benefit, unacceptable toxicity, withdrawal of consent or death. Enrollment to Cohort C is complete.	Drug: Atezolizumab; 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
Active Comparator: Cohort C: Pemetrexed, Cisplatin or Carboplatin; This cohort includes participants with bTMB positive, non-squamous NSCLC. Participants will receive 4 or 6 cycles of treatment, with each cycle being 21 days in duration. Carboplatin at a dose of area under the concentration-time curve (AUC) of 5 or 6 IV or cisplatin at a dose of 75 milligrams per meter square (mg/m^2) IV on Day 1 of each cycle combined with pemetrexed at a dose of 500 mg/m^2 IV on Day 1 of each cycle. Pemetrexed may be continued as maintenance therapy every 21 days (Q21D) as per local standard of care. Enrollment to Cohort C is complete.	Drug: Pemetrexed; Participants will receive pemetrexed 500 mg/m^2 IV infusion on Day 1 Q21D.; Drug: Cisplatin; Participants will receive cisplatin 75 mg/m^2 IV on Day 1 Q21D.; Drug: Carboplatin; Participants will receive carboplatin of AUC 5 or 6 IV on Day 1 Q21D.
Active Comparator: Cohort C: Gemcitabine, Cisplatin or Carboplatin; This cohort includes participants with bTMB positive, squamous NSCLC. Participants will receive 4 or 6 cycles of treatment, with each cycle being 21 days in duration. Gemcitabine 1250 mg/m^2 IV on Days 1 and 8 of every cycle and cisplatin 75 mg/m^2 IV on Day 1 Q21D or gemcitabine 1000 mg/m^2 IV on Days 1 and 8 of every cycle and carboplatin AUC 5 IV on Day 1 Q21D. Enrollment to Cohort C is complete.	Drug: Cisplatin; Participants will receive cisplatin 75 mg/m^2 IV on Day 1 Q21D.; Drug: Carboplatin; Participants will receive carboplatin of AUC 5 or 6 IV on Day 1 Q21D.; Drug: Gemcitabine; Participants will receive gemcitabine 1000 or 1250 mg/m^2 on Days 1 and 8 of every cycle (1 Cycle=21 days).
Experimental: Cohort D: Entrectinib 600 Milligrams (mg); This cohort includes participants with c-ros oncogene 1 positive (ROS1+) NSCLC. Participants will receive entrectinib 600 mg orally once a day (QD) until disease progression, unacceptable toxicity, withdrawal of consent or death. Enrollment to Cohort D is complete.	Drug: Entrectinib; Participants will receive entrectinib 600 mg orally QD.; Other Names: RO7102122
Experimental: Cohort E: Atezolizumab, Vemurafenib, and Cobimetinib; This cohort includes participants with BRAF V600 mutation. Participants will receive: atezolizumab 1680 mg IV Q4W after the run-in period; cobimetinib 60 mg orally (PO) QD on Days 1-21 of each cycle during the run-in and triple-combination periods; and vemurafenib 960 mg PO twice daily (BID) on Days 1-21 of the initial run-in period, then 720 mg PO BID on Days 1-22 of the initial run-in period and on Days 1-28 of each cycle during the triple-combination period. Enrollment to Cohort E is complete.	Drug: Atezolizumab; 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; Drug: Cobimetinib; Participants will receive 60 mg PO QD on Days 1-21 of the initial run-in and triple-combination periods.; Other Names: RO5514041; Drug: Vemurafenib; 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
Experimental: Cohort F: Atezolizumab, Bevacizumab, Carboplatin, and Pemetrexed; This cohort includes participants with EGFR exon 20+ NSCLC. Participants will receive atezolizumab + bevacizumab + carboplatin + pemetrexed for 4 or 6 induction cycles (cycle = 21 days). After induction therapy, participants will continue maintenance treatment with atezolizumab + bevacizumab + pemetrexed until disease progression, unacceptable toxicity, withdrawal of consent, or death. Enrollment to Cohort F is complete.	Drug: Atezolizumab; 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; Drug: Pemetrexed; Participants will receive pemetrexed 500 mg/m^2 IV infusion on Day 1 Q21D.; Drug: Carboplatin; Participants will receive carboplatin of AUC 5 or 6 IV on Day 1 Q21D.; Drug: Bevacizumab; 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
Experimental: Cohort G: Divarasib or Docetaxel; Experimental: Cohort G: GDC-6036 or Docetaxel This cohort includes participants with KRAS G12C mutation. Participants will receive GDC-6036 PO QD or IV docetaxel Q3W (75 mg/m^2) until disease progression or unacceptable toxicity New participants will no longer receive docetaxel.	Drug: Docetaxel; Participants will receive IV docetaxel Q3W (75 mg/m^2) until disease progression or unacceptable toxicity; Drug: Divarasib; Participants will receive divarasib PO QD until disease progression or unacceptable toxicity.; Other Names: RO7435846; GDC-6036
No Intervention: Cohort Z: Natural History Cohort; Participants with genomic profiles of interest that are not enrolled in the other cohorts will enter into natural history follow-up.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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	Baseline up to disease progression or death (up to approximately 6 years)
Cohort B: Percentage of Participants with Confirmed Objective Response as Assessed by the Investigator Based on RECIST v1.1	Baseline up to disease progression or death (up to approximately 6 years)
Cohort C: Progression Free Survival (PFS) as Assessed by the Investigator Based on RECIST v1.1 in bTMB PP1	Baseline up to disease progression or death (up to approximately 6 years)
Cohort D: Percentage of Participants with Confirmed Objective Response as Assessed by the Investigator Based on RECIST v1.1	Baseline up to disease progression or death (up to approximately 6 years)
Cohort E: Time in Response (TIR) as Assessed by the Investigator Based on RECIST v1.1	Month 12
Cohort F: Investigator-Assessed Objective Response Rate (ORR) Based on RECIST v1.1	Baseline up to disease progression or death (up to approximately 6 years)
Cohort G: Incidence of Adverse Events (AEs)	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cohorts A, B and D: Percentage of Participants with Clinical Benefit Response as Assessed by the Investigator Based on RECIST v1.1		Baseline up to disease progression or death (up to approximately 6 years)
Cohorts A-F: Duration of Response as Assessed by the Independent Review Facility (IRF) Based on RECIST v1.1		Baseline up to disease progression or death (up to approximately 6 years)
Cohorts A, B and D: Percentage of Participants with Clinical Benefit Response as Assessed by IRF Based on RECIST v1.1		Baseline up to disease progression or death (up to approximately 6 years)
Cohorts A-F: PFS as Assessed by IRF Based on RECIST v1.1		Baseline up to disease progression or death (up to approximately 6 years)
Cohorts A-F: Percentage of Participants with Confirmed Objective Response as Assessed by IRF Based on RECIST v1.1		Baseline up to disease progression or death (up to approximately 6 years)
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)		Baseline, every 4 weeks through Cycle 6 (1 Cycle = 21 or 28 days), every 8 weeks thereafter up to approximately 6 years
Cohorts A-F: Time to Deterioration in Patient-Reported Lung Cancer Symptoms (Cough, Dyspnea and Chest Pain) as Measured by the SILC Scale		Baseline, every 4 weeks through Cycle 6 (1 Cycle = 21 or 28 days), every 8 weeks thereafter up to approximately 6 years
Cohorts C, E, F: Change from Baseline in Patient-Reported Lung Cancer Symptom (Cough, Dyspnea, Chest pain) Score as Measured by the SILC Scale		Baseline, every 4 weeks through Cycle 6 (1 Cycle = 21 or 28 days), every 8 weeks thereafter up to approximately 6 years
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)		Baseline, every 4 weeks through Cycle 6 (1 Cycle = 21 or 28 days), every 8 weeks thereafter up to approximately 6 years
Cohorts A, B, D, E, F: Change from Baseline in HRQoL Scores as Measured by the SILC Scale		Baseline, every 4 weeks through Cycle 6 (1 Cycle = 21 or 28 days), every 8 weeks thereafter up to approximately 6 years
Cohorts A, B, D, E, F: Change from Baseline in Patient Functioning and Symptoms Score as Measured by the SILC Scale		Baseline, every 4 weeks through Cycle 6 (1 Cycle = 21 or 28 days), every 8 weeks thereafter up to approximately 6 years
Cohort B: Percentage of Participants with Dose-Limiting Toxicities (DLTs)		Day 1 to Day 28 of Cycle 1 (cycle length = 28 days)
Cohort B: Maximum Plasma Concentration (Cmax) of Alectinib	DFP: Dose-Finding Phase; DEP: Dose-Expanding Phase.	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)
Cohort B: Area Under the Concentration-Time Curve from Time Zero to the Last Measurable Concentration (AUC0-last) of Alectinib		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)
Cohort B: Time to Reach Cmax (Tmax) of Alectinib		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)
Cohort B: Half-Life (t1/2) of Alectinib		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)
Cohort B: Metabolite to Parent Exposure Ratio for AUC0-last		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)
Cohort B: Metabolite to Parent Exposure Ratio for Cmax		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)
Cohort C: Percentage of Participants with Objective Response as Assessed by the Investigator Based on RECIST v1.1		Baseline up to disease progression or death (up to approximately 6 years)
Cohort C: Percentage of Participants Free from Disease Progression as Assessed by the Investigator Based on RECIST v1.1 at Months 6 and 12		Months 6, 12
Cohort C: PFS as Assessed by the Investigator based on RECIST v1.1 in bTMB PP2		Baseline up to disease progression or death (up to approximately 6 years)
Cohort C: OS in bTMB PP2		Baseline up to approximately 6 years
Cohort D: Time to CNS progression as Assessed by the Investigator Based on RECIST v1.1		Baseline up to CNS progression (up to approximately 6 years)
Cohort D: Time to CNS progression as Assessed by the IRF Based on RECIST v1.1		Baseline up to CNS progression (up to approximately 6 years)
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		Baseline, every 4 weeks until disease progression, up to approximately 6 years
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		Baseline, every 4 weeks until disease progression, up to approximately 6 years
Cohort D: Mean Plasma Concentration of Entrectinib		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).
Cohort D: Mean Plasma Concentration of Entrectinib Metabolite M5		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).
Cohort E: TIR as Assessed by the Investigator Based on RECIST v1.1		Month 9
Cohort E: TIR as Assessed by IRF		Month 12
Cohorts E, F: Serum Concentration of Atezolizumab		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)
Cohorts E, F: Change from Baseline in Anti-Drug Antibodies (ADAs)		Baseline up to approximately 6 years
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)		Baseline up to approximately 6 years
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		Baseline up to approximately 6 years
Cohorts A-F: Duration of Response (DOR) as Assessed by the Investigator Based on RECIST v1.1		Baseline up to disease progression or death (up to approximately 6 years)
Cohorts A, B, D, F: PFS as Assessed by the Investigator Based on RECIST v1.1		Baseline up to disease progression or death (up to approximately 6 years)
Cohorts A-F: Overall Survival (OS)		Baseline up to approximately 6 years
Cohorts A-F: Percentage of Participants with Adverse Events (AEs)		Baseline up to approximately 6 years
Cohorts A-F: Change from Baseline in Patient Functioning and Symptoms Score as Measured by the EORTC QLQ-C30		Baseline, every 4 weeks through Cycle 6 (1 Cycle = 21 or 28 days), every 8 weeks thereafter up to approximately 6 years
Cohorts A-F: Health Status Assessed as an Index Score Using the European Quality of Life 5-Dimension 5-Level (EQ-5D-5L) Questionnaire		Baseline, every 4 weeks through Cycle 6 (1 Cycle = 21 or 28 days), every 8 weeks thereafter up to approximately 6 years
Cohort G: Plasma Concentration of Divarasib		Baseline up to approximately 6 years

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Publications and helpful links

General Publications

• Peters S, Dziadziuszko R, Morabito A, Felip E, Gadgeel SM, Cheema P, Cobo M, Andric Z, Barrios CH, Yamaguchi M, Dansin E, Danchaivijitr P, Johnson M, Novello S, Mathisen MS, Shagan SM, Schleifman E, Wang J, Yan M, Mocci S, Voong D, Fabrizio DA, Shames DS, Riehl T, Gandara DR, Mok T. Atezolizumab versus chemotherapy in advanced or metastatic NSCLC with high blood-based tumor mutational burden: primary analysis of BFAST cohort C randomized phase 3 trial. Nat Med. 2022 Sep;28(9):1831-1839. doi: 10.1038/s41591-022-01933-w. Epub 2022 Aug 22.
• Peters S, Gadgeel SM, Mok T, Nadal E, Kilickap S, Swalduz A, Cadranel J, Sugawara S, Chiu CH, Yu CJ, Moskovitz M, Tanaka T, Nersesian R, Shagan SM, Maclennan M, Mathisen M, Bhagawati-Prasad V, Diarra C, Assaf ZJ, Archer V, Dziadziuszko R. Entrectinib in ROS1-positive advanced non-small cell lung cancer: the phase 2/3 BFAST trial. Nat Med. 2024 Jul;30(7):1923-1932. doi: 10.1038/s41591-024-03008-4. Epub 2024 Jun 19.
• Wang HY, Ho CC, Lin YT, Liao WY, Chen CY, Shih JY, Yu CJ. Comprehensive Genomic Analysis of Patients With Non-Small-Cell Lung Cancer Using Blood-Based Circulating Tumor DNA Assay: Findings From the BFAST Database of a Single Center in Taiwan. JCO Precis Oncol. 2024 Jan;8:e2300314. doi: 10.1200/PO.23.00314.

Study record dates

Study Major Dates

• Study Start (Actual): September 22, 2017
• Primary Completion (Estimated): October 31, 2026
• Study Completion (Estimated): October 31, 2026

Study Registration Dates

• First Submitted: June 5, 2017
• First Submitted That Met QC Criteria: June 5, 2017
• First Posted (Actual): June 7, 2017

Study Record Updates

• Last Update Posted (Actual): March 9, 2026
• Last Update Submitted That Met QC Criteria: March 6, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; Amino Acids, Peptides, and Proteins; Proteins; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Amides; Indoles; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Inorganic Chemicals; Chlorine Compounds; Nitrogen Compounds; Coordination Complexes; Guanine; Hypoxanthines; Purinones; Purines; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic; Taxoids; Cyclodecanes; Diterpenes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Platinum Compounds; Sulfonamides; Sulfones; Docetaxel; Bevacizumab; Pemetrexed; Vemurafenib; Gemcitabine; Carboplatin; Cisplatin; atezolizumab; cobimetinib; entrectinib; alectinib
• Other Study ID Numbers: BO29554; 2017-000076-28 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data_sharing

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No