A Study Evaluating the Efficacy and Safety of Multiple Therapies in Cohorts of Participants With Locally Advanced, Unresectable, Stage III Non-Small Cell Lung Cancer (NSCLC)

Non-Small Cell Lung Cancer Clinical Trial

Official title:

A Phase I-III, Multicenter Study Evaluating the Efficacy and Safety of Multiple Therapies in Cohorts of Patients Selected According to Biomarker Status, With Locally Advanced, Unresectable, Stage III Non-Small Cell Lung Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05170204
• Other study ID #: BO42777
• Status: Recruiting
• Phase: Phase 3
• Start date: November 1, 2022
• Est. completion date: April 14, 2035

Study information

• Verified date: June 2024
• Source: Hoffmann-La Roche
• Contact: Reference Study ID Number: BO42777 https://forpatients.roche.com
• Phone: 888-662-6728
• Email: global-roche-genentech-trials[@]gene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will evaluate the efficacy and safety of multiple therapies in participants with locally advanced, unresectable, Stage III NSCLC with eligible biomarker status as determined by Version 8 of the American Joint Committee on Cancer/Union for International Cancer Control NSCLC staging system.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 121
• Est. completion date: April 14, 2035
• Est. primary completion date: June 17, 2029
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria (All Cohorts):

• Body weight >/= 30 kg at screening

• Willingness and ability to use the electronic device(s) or application(s) for the electronic patient-reported outcome (PRO)

• Whole-body positron emission tomography/computed tomography scan (PET/CT) (from the base of skull to mid-thighs) for the purposes of staging, performed prior and within 42 days of the first dose of cCRT or sCRT

• Histologically or cytologically documented locally advanced, unresectable Stage III NSCLC of either squamous or non-squamous histology

• Prior receipt of at least two prior cycles of platinum-based chemotherapy given concurrently with radiotherapy (cCRT); or at least two prior cycles of platinum-based chemotherapy given prior to radiotherapy (sCRT)

• The RT component in the cCRT or sCRT must have been at a total dose of radiation of 60 (+/-10%) Gy (54 Gy to 66 Gy) administered by intensity-modulated radiotherapy (preferred) or three dimension (3D)-conforming technique

• No disease progression during or following platinum-based cCRT or sCRT

• Life expectancy >/= 12 weeks

• Confirmed availability of a representative formalin-fixed, paraffin-embedded (FFPE) tumor specimen

• Documented tumor PD-L1 status (TC score < 1% vs. >/= 1% vs. unknown) as determined:

centrally with the SP263 IHC assay on the confirmed available FFPE tumor specimen; locally, with the SP263 (preferred) or 22C3 IHC assays

• Eastern Cooperative Oncology Group Performance Status of 0, 1, or 2

• Adequate hematologic and end-organ function

• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception, and agreement to refrain from donating eggs, as defined by the protocol

• For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agreement to refrain from donating sperm, as defined by the protocol

Inclusion criteria specific to Cohort A1:

• Documented ALK fusion positivity by an eligible result from: centralized multiplex molecular testing of tumor tissue at the Sponsor's designated central laboratory under Study BX43361 or available results from a Sponsor pre-approved local, appropriately validated ALK fusion test on tumor tissue performed in a Clinical Laboratory Improvement Amendments certified or equivalent laboratory

Inclusion criteria specific to Cohort A2:

• Documented ROS1 fusion positivity by an eligible result from: centralized multiplex molecular testing of tumor tissue at the Sponsor's designated central laboratory under Study BX43361 or available results from a Sponsor pre-approved local, appropriately validated ROS1 fusion test on tumor tissue performed in a Clinical Laboratory Improvement Amendments certified or equivalent laboratory

• Ability to swallow entrectinib intact, without chewing, crushing, or opening the capsules

Exclusion Criteria (All Cohorts):

• Any history of previous NSCLC and/or any history of prior treatment for NSCLC (patients must be newly diagnosed with unresectable Stage III disease)

• Any evidence of Stage IV disease, including, but not limited to, the following:

pleural effusion, pericardial effusion, brain metastases, history of intracranial hemorrhage or spinal cord hemorrhage, bone metastases, distant metastases

• If a pleural effusion is present, the following criteria must be met to exclude malignant involvement (T4 disease): when pleural fluid is visible on both the CT scan and chest X-ray, a pleuracentesis is required to confirm that the pleural fluid is cytologically negative; participants with exudative pleural effusions are excluded regardless of cytology; participants with effusions that are minimal (i.e., not visible on chest X-ray) that are too small to safely tap are eligible

• NSCLC known to have a known or likely oncogenic-driver mutation in the EGFR gene, as identified by site local testing or Sponsor central testing

• Liver disease, characterized by any of the following: impaired excretory function (e.g., hyperbilirubinemia), synthetic function, or other conditions of decompensated liver disease, such as coagulopathy, hepatic encephalopathy, hypoalbuminemia, ascites, and bleeding from esophageal varices or active viral or active autoimmune, alcoholic, or other types of acute hepatitis

• Positive hepatitis B surface antigen (HBsAg) test at screening

• Participants known to be positive for hepatitis C virus (HCV) antibody (Ab) are excluded with the following exception: participants who are HCV Ab positive but HCV RNA negative due to prior treatment or natural resolution are eligible

• HIV infection: participants are excluded if not well-controlled as defined by the protocol

• Known active tuberculosis

• History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on the screening chest CT scan

• Grade >/= 2 pneumonitis from prior cCRT or sCRT

• Any Grade > 2 unresolved toxicity from prior cCRT or sCRT

• Any gastrointestinal (GI) disorder that may affect absorption of oral medications, such as malabsorption syndrome or status post-major bowel resection

• Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications

• Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis, with the following exceptions: participants with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study; participants with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study

• History of malignancy other than NSCLC within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death (e.g., 5-year OS rate > 90%), such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal breast carcinoma in situ, or Stage I uterine cancer

• Any concurrent chemotherapy, immunotherapy, biologic, or hormonal therapy for cancer

• Major surgical procedure, within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the study

• Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin-2) within 4 weeks or 5 drug-elimination half-lives (whichever is longer) prior to initiation of study treatment

• Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during study treatment or within 5 months after the final dose of study treatment

• Treatment with investigational therapy within 28 days prior to initiation of study treatment

• Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor-alpha agents) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during study treatment, with exceptions defined by the protocol

• Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-cytotoxic T lymphocyte-associated protein 4, anti-TIGIT, anti-PD-1, and anti-PD-L1 therapeutic antibodies

• Prior allogeneic stem cell or solid organ transplantation

• Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or the follow-up period of an interventional study

• Any condition that, in the opinion of the investigator, would interfere with the evaluation of the study drug or interpretation of patient safety or study results

• Any prior Grade >/= 3 immune-mediated adverse event or any unresolved Grade > 1 immune-mediated adverse event while receiving any previous immunotherapy agent other than immune checkpoint blockade agents

Exclusion criteria specific to Cohort A1:

• Presence of clinically symptomatic interstitial lung disease or interstitial pneumonitis, including radiation pneumonitis (i.e., affecting activities of daily living or requiring therapeutic intervention)

• NSCLC known to have one or more of the following ALK point mutations, as identified by site local testing or Sponsor central testing: I1171X (where X is any other amino acid), V1180L, G1202R

• Symptomatic bradycardia

• Significant cardiovascular disease (such as New York Heart Association Class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident) within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina; participants with known coronary artery disease, congestive heart failure not meeting the above criteria, or left ventricular ejection fraction < 50% must be on a stable medical regimen that is optimized in the opinion of the treating physician, in consultation with a cardiologist if appropriate

• Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia

• Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment

• Prior treatment with ALK inhibitors

• History of hypersensitivity to alectinib, durvalumab, or any of their excipients

• Inability to swallow oral study drug

• Known hereditary problems of galactose intolerance, a congenital lactase deficiency, or glucose-galactose malabsorption

• Pregnancy or breastfeeding, or intending to become pregnant during the study treatment or within 90 days after the final dose of alectinib or durvalumab

Exclusion criteria specific to Cohort A2:

• Symptomatic bradycardia

• Significant cardiovascular disease (such as New York Heart Association Class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident) within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina; participants with known coronary artery disease, congestive heart failure not meeting the above criteria, or left ventricular ejection fraction < 50% must be on a stable medical regimen that is optimized in the opinion of the treating physician, in consultation with a cardiologist if appropriate

• Left ventricular ejection fraction less than or equal to 50% observed during the screening for the study

• History of prolonged QTc interval (e.g., repeated demonstration of a QTc interval > 450 ms from ECGs performed at least 24 hours apart)

• History of additional risk factors for torsade de pointes (e.g., family history of long QT syndrome)

• Familial or personal history of congenital bone disorders or bone metabolism alterations

• Incomplete recovery from any surgery prior to the start of study treatment that would interfere with the determination of safety or efficacy of the treatment

• Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia

• Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment

• Prior treatment with ROS1 inhibitors

• History of hypersensitivity to entrectinib, durvalumab, and their excipients

• Grade >/= 3 toxicities due to any prior therapy (e.g., RT) (excluding alopecia) that have not shown improvement or are not stable and are considered to interfere with current study drug

• Known hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption

• Grade >/= 2 peripheral neuropathy

• Pregnancy or intention of becoming pregnant during study treatment, within 35 days after the final dose of entrectinib, or within 90 days after the final dose of durvalumab

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Small Cell Lung Cancer

Intervention

Drug:
• Alectinib
Participants will receive oral alectinib twice daily with food.
• Entrectinib
Participants will receive oral entrectinib once daily, with or without food.
• Durvalumab
Participants will receive IV durvalumab every 4 weeks.

Locations

Country	Name	City	State
Australia	Lifehouse	Camperdown	New South Wales
Australia	Peter MacCallum Cancer Centre; Medical Oncology	Melbourne	Victoria
Australia	One Clinical Research	Nedlands	Western Australia
Australia	Northern Cancer Institute	St Leonards	New South Wales
Australia	Westmead Hospital; Medical Oncology and Pallative Care	Westmead	New South Wales
Belgium	GHdC Site Notre Dame	Charleroi
Belgium	UZ Gent	Gent
Brazil	Hospital de Cancer de Barretos	Barretos	SP
Brazil	Oncocentro Belo Horizonte	Belo Horizonte	MG
Brazil	Clínica de Oncologia Reichow	Blumenau	SC
Brazil	Crio - Centro Regional Integrado de Oncologia	Fortaleza	CE
Brazil	Hospital Nossa Senhora da Conceicao	Porto Alegre	RS
Brazil	Santa Casa de Misericordia de Porto Alegre	Porto Alegre	RS
Brazil	Oncoclinicas Rio de Janeiro S.A.	Rio de Janeiro	RJ
Brazil	Hospital Sao Rafael - HSR	Salvador	BA
Brazil	Instituto do Cancer do Estado de Sao Paulo - ICESP	Sao Paulo	SP
Brazil	COT - Centro Oncologico do Triangulo	Uberlandia	MG
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario
Chile	Centro de Estudios Clínicos SAGA	Santiago
Chile	OrlandiOncología	Santiago
Chile	James Lind Centro de Investigación Del Cáncer	Temuco
China	Beijing Cancer Hospital	Beijing
China	Hunan Cancer Hospital	Changsha CITY
China	Hunan Cancer Hospital	Changsha CITY
China	Xinqiao Hospital of Third Military Medical University	Chongqing City
China	Shandong Cancer Hospital	Jinan
China	Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School	Nanjing City
China	The affiliated hospital of Qingdao university	Qingdao City
China	Shanghai Pulmonary Hospital	Shanghai
China	Tianjin Medical University Cancer Institute & Hospital	Tianjin
China	Union Hospital Tongji Medical College Huazhong University of Science and Technology	Wuhan City
China	Shanxi Cancer Hospital	Xi'an
Colombia	Clinica De La Costa	Barranquilla
Colombia	Fundacion Cardioinfantil	Bogota
Colombia	Hospital Universitario San Ignacio	Bogota
Colombia	Fundación CTIC - Centro de Tratamiento e Investigación sobre Cáncer Luis Carlos Sarmiento Angulo	Bogota, D.C.
Colombia	Instituto Cancerologia Medellin; Clinica Las Americas	Medellin
Costa Rica	Clinica CIMCA	San José
Costa Rica	ICIMED Instituto de Investigación en Ciencias Médicas	San José
France	CHU Angers,Service de Pneumologie	Angers
France	CENTRE FRANCOIS BACLESSE; Oncologie- Pneumologie	Caen
France	Centre Leon Berard	Lyon
France	Hopital Nord; Pneumologie	Marseille cedex 20
France	Hôpitaux D'Instruction Des Armees Begin	St Mande
France	Hia Sainte Anne; Pneumologie	Toulon
France	CHU de Toulouse - Hôpital Larrey	Toulouse
Germany	Helios Klinikum Emil von Behring GmbH	Berlin
Germany	Klinikum Chemnitz gGmbH	Chemnitz
Germany	Klinikum Esslingen; Klinik für Kardiologie, Angiologie und Pneumologie	Esslingen
Germany	Thoraxklinik Heidelberg gGmbH	Heidelberg
Germany	LMU Klinikum der Universität München, Medizinische Klinik und Poliklinik V, Campus Innenstadt	München
Germany	Universitätsklinikum Regensburg; Klinik und Poliklinik für Innere Medizin II, Pneumologie	Regensburg
Hong Kong	Queen Mary Hospital; Dept. of Clinical Oncology	Hong Kong
Israel	Rambam Medical Center; Oncology	Haifa
Israel	Rabin Medical Center-Beilinson Campus; Davidof Institute	Petach Tikva
Italy	ASST DEGLI SPEDALI CIVILI DI BRESCIA; Oncologia Medica	Brescia	Lombardia
Italy	Azienda Ospedaliero-Universitaria Careggi; SOD Radioterapia	Firenze	Toscana
Italy	IRCCS A.O.U San MArtino - IST; U.O. Oncologia Medica 2	Genova	Liguria
Italy	IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola; Oncologia Medica	Meldola	Emilia-Romagna
Italy	Asst Grande Ospedale Metropolitano Niguarda; Dipartimento Di Ematologia Ed Oncologia	Milano	Lombardia
Italy	Irccs Istituto Europeo di Oncologia (IEO); Divisione di Oncologia	Milano	Lombardia
Italy	A.O. UNIVERSITARIA S. LUIGI GONZAGA; Oncologia Medica	Orbassano	Piemonte
Italy	IRCCS Istituto Oncologico Veneto (IOV); Oncologia Medica Seconda	Padova	Veneto
Italy	Ospedale P. Pederzoli Casa di cura Privata; Lung Unit Thoracic 3° Floor	Peschiera Del Garda (VR)	Veneto
Italy	Azienda Ospedaliera San Camillo Forlanini; U.O.C. Pneumologia Ad Indirizzo Oncologico 1	Roma	Lazio
Italy	IRCCS Istituto Regina Elena (IFO); Oncologia Medica B	Roma	Lazio
Japan	Aichi Cancer Center Hospital	Aichi
Japan	Hirosaki University Hospital	Aomori
Japan	National Cancer Center East	Chiba
Japan	Shikoku Cancer Center	Ehime
Japan	Kurume University Hospital	Fukuoka
Japan	NHO Kyushu Cancer Center	Fukuoka
Japan	Kobe City Medical Center General Hospital	Hyogo
Japan	National Hospital Organization Himeji Medical Center	Hyogo
Japan	Kagoshima University Hospital	Kagoshima
Japan	Kanagawa Cancer Center	Kanagawa
Japan	Kumamoto University Hospital	Kumamoto
Japan	Sendai Kousei Hospital	Miyagi
Japan	Nara Medical University Hospital	Nara
Japan	Niigata Cancer Center Hospital	Niigata
Japan	Kurashiki Central Hospital	Okayama
Japan	Okayama University Hospital	Okayama
Japan	NHO Kinki Chuo Chest Medical Center	Osaka
Japan	Osaka City General Hospital	Osaka
Japan	Osaka International Cancer Institute	Osaka
Japan	Kindai University Hospital ; Faculty of Medicine	Osaka-sayama
Japan	Shizuoka Cancer Center	Shizuoka
Japan	Juntendo University Hospital	Tokyo
Japan	Komagome Hospital	Tokyo
Japan	The Cancer Institute Hospital of JFCR	Tokyo
Japan	Tottori University Hospital	Tottori
Japan	National Hospital Organization Yamaguchi - Ube Medical Center	Yamaguchi
Korea, Republic of	Chungbuk National University Hospital	Cheongju si
Korea, Republic of	Kyungpook National University Chilgok Hospital	Daegu
Korea, Republic of	Pusan National University Yangsan Hospital	Gyeongsangnam-do
Korea, Republic of	Chonnam National University Hwasun Hospital	Jeollanam-do
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Kangbuk Samsung Hospital	Seoul
Korea, Republic of	Korea University Guro Hospital	Seoul
New Zealand	Auckland City Hospital, Cancer and Blood Research	Auckland
Norway	Oslo universitetssykehus HF, Ullevål, Kreftsenteret	Oslo
Poland	Instytut Genetyki i Immunologii GENIM	Lublin
Poland	Warminsko-Mazurskie Centrum Chorób P?uc w Olsztynie; Oddzial onkologii z pododdzialem chemioterapii	Olsztyn
Poland	Wielkopolskie Centrum Pulmonologii i Torakochirurgii w Poznaniu	Poznan
Poland	Narod.Inst.Onkol. im. M.Sklodowskiej - Curie-Panst.Inst.Bad; Klinika Nowot.Pluca i Klatki Piers	Warszawa
Poland	Dolno?l?skie Centrum Chorób P?uc we Wroc?awiu; Oddzia? Onkologii Klinicznej VII	Wroc?aw
Serbia	Hospital Medical Center Bezanijska kosa; Clinic for Medical Oncology	Belgrade
Serbia	University Clinical Centre of Serbia; Clinic for Pulmonology	Belgrade
Serbia	Univ Clinical Center Kragujevac; Clinic for Pulmonology	Kragujevac
Serbia	Institute for Pulmonary Diseases of Vojvodina; Clinic for Pulmonary Oncology	Sremska Kamenica
Singapore	National Cancer Centre; Medical Oncology	Singapore
Singapore	Tan Tock Seng Hospital; Oncology	Singapore
Spain	Complejo Hospitalario Universitario A Coruña (CHUAC); Servicio de Oncologia	A Coruña	LA Coruña
Spain	Hospital General Univ. de Alicante; Servicio de Oncologia	Alicante
Spain	Hospital Universitari Vall d'Hebron; Oncology	Barcelona
Spain	Complejo Hospitalario Universitario Insular?Materno Infantil; Servicio de Oncologia	Las Palmas de Gran Canaria	LAS Palmas
Spain	Hospital Ramon y Cajal; Servicio de Oncologia	Madrid
Spain	Hospital Universitario 12 de Octubre; Servicio de Oncologia	Madrid
Spain	Hospital Universitario La Paz; Servicio de Oncologia	Madrid
Spain	Hospital Regional Universitario Carlos Haya; Servicio de Oncologia	Malaga
Spain	Hospital Universitario Virgen del Rocio; Servicio de Oncologia	Sevilla
Spain	Hospital Clínico Universitario de Valencia; Servicio de Oncología	Valencia
Sweden	Sahlgrenska University Hospital; Sahlgrenska Clinical Trial unit / Department of Oncology	Göteborg
Sweden	Karolinska Universitetssjukhuset, Solna; Kliniska prövningsenheten Z:4:01	Stockholm
Taiwan	Taipei Medical University ?Shuang Ho Hospital	New Taipei City
Taiwan	National Cheng Kung Univ Hosp	Tainan
Taiwan	Taipei Medical University Hospital	Taipei
Taiwan	Taipei Municipal Wan Fang Hospital	Taipei
Taiwan	National Taiwan Uni Hospital	Taipei City
Taiwan	Taipei Veterans General Hospital	Taipei City
Taiwan	Chang Gung Memorial Hospital - Linkou	Taoyuan
Taiwan	Taichung Veterans General Hospital	Xitun Dist.
Thailand	Faculty of Med. Siriraj Hosp.; Med.-Div. of Med. Oncology	Bangkok
Thailand	Rajavithi Hospital; Division of Medical Oncology	Bangkok
Thailand	Oncology Unit, Faculty of Medicine, Vajira Hospital; Department of Medicine	Dusit
Thailand	Songklanagarind Hospital; Department of Internal Medicine, Division of Respiratory	Songkhla
Turkey	Baskent University Adana Dr. Turgut Noyan Practice and Research Hospital; Medical Oncology	Adana
Turkey	Gazi Uni Medical Faculty Hospital; Oncology Dept	Ankara
Turkey	Liv Hospital Ankara; Medical Oncology	Ankara
Turkey	Bakirkoy Dr. Sadi Konuk Egitim ve Arastirma Hastanesi, Tibbi Onkoloji	Bakirkoy / Istanbul
Turkey	Ataturk University Medical Faculty Yakutiye Research Hospital Medical Oncology Department	Erzurum
Turkey	Istanbul Uni Cerrahpasa Medical Faculty Hospital; Medical Oncology	Istanbul
Turkey	Marmara Uni Faculty of Medicine; Medical Oncology	Istanbul
Turkey	Medipol University Medical Faculty; Oncology Department	Istanbul
Turkey	Medikal Park Samsun	Samsun
United Kingdom	Birmingham Heartlands Hospital	Birmingham
United Kingdom	Velindre Cancer Centre; Oncology Dept	Cardiff
United Kingdom	Barts & London School of Med; Medical Oncology	London
United Kingdom	Royal Marsden Hospital; Dept of Med-Onc	London
United Kingdom	Christie Hospital Nhs Trust; Medical Oncology	Manchester
United States	University Of Michigan	Ann Arbor	Michigan
United States	Virginia Cancer Specialists (Fairfax) - USOR	Fairfax	Virginia
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Thompson Cancer Survival Center	Knoxville	Tennessee
United States	Rocky Mountain Cancer Centers - Lone Tree	Lone Tree	Colorado
United States	Baptist Cancer Center	Memphis	Tennessee
United States	Mount Sinai Medical Center; Comprehensive Cancer Center	Miami Beach	Florida
United States	University of South Alabama; Mitchell Cancer Institute	Mobile	Alabama
United States	Hillman Cancer Center;Medical Oncology	Pittsburgh	Pennsylvania
United States	Oregon Health Sciences Uni	Portland	Oregon
United States	Mays Cancer Center, UT Health San Antonio	San Antonio	Texas
United States	Southern California Kaiser Permanente	San Diego	California
United States	Northwest Cancer Specialists, P.C.	Tigard	Oregon

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Brazil,  Canada,  Chile,  China,  Colombia,  Costa Rica,  France,  Germany,  Hong Kong,  Israel,  Italy,  Japan,  Korea, Republic of,  New Zealand,  Norway,  Poland,  Serbia,  Singapore,  Spain,  Sweden,  Taiwan,  Thailand,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival (PFS)		From randomization to the first documented disease progression as determined by blinded independent central review (BICR) per Response Evaluation Criterial in Solid Tumors (RECIST) v1.1, or death from any cause, whichever occurs first (up to 3 years)
Secondary	Time-to-confirmed deterioration (TTCD)		From randomization to the first deterioration of >/= 10 points that is either maintained for two consecutive assessments or followed by death from any cause within 3 weeks (up to 3 years)
Secondary	Proportion of participants who have maintained or improved baseline health as measured by the European Organisation for the Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ)-C30 physical functioning and role functioning scales		5, 11, and 17 months
Secondary	Proportion of participants who have maintained or improved from their baseline health in cough, chest pain, and dyspnea symptoms as measured using the EORTC QLQ-LC13		5, 11, and 17 months
Secondary	Percentage of participants with adverse events (AEs)		Up to 3 years
Secondary	Time to central nervous system (CNS) progression		From randomization to the first occurrence of disease progression in the CNS as determined by BICR per RECIST v1.1 (up to 3 years)
Secondary	Distant metastasis-free survival (DMFS)		From randomization to the first occurrence of distant metastasis or death (whichever occurs first) as determined by BICR per RECIST v1.1 (up to 3 years)
Secondary	Objective response rate (ORR), defined as the percentage of participants with measurable disease who attain a complete response (CR) or partial response (PR) as determined by the investigator per RECIST v1.1		Up to 3 years
Secondary	PFS		From randomization to the first documented disease progression as determined by the investigator per RECIST v1.1, or death from any cause, whichever occurs first (up to 3 years)
Secondary	Duration of response (DOR)		From the first documented CR or PR to the first documented disease progression or death (whichever occurs first) as determined by the investigator per RECIST v1.1 (up to 3 years)
Secondary	ORR, defined as the percentage of participants with measurable disease who attain a CR or PR as determined by BICR per RECIST v1.1		Up to 3 years
Secondary	DOR		From the first documented CR or PR to the first documented disease progression or death (whichever occurs first) as determined by BICR per RECIST v1.1 (up to 3 years)
Secondary	Overall survival (OS)		From randomization to death from any cause (up to 5 years)
Secondary	Time to CNS progression		From randomization to the first occurrence of disease progression in the CNS as determined by the investigator per RECIST v1.1 (up to 3 years)