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)

Phase 3

Recruiting

• Conditions: Non-Small Cell Lung Cancer
• Interventions: Drug: Durvalumab; Drug: Alectinib; Drug: Entrectinib

• Registration Number: NCT05170204
• Lead Sponsor: Hoffmann-La Roche

Brief 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-12-22
• Study First Submitted QC: 2021-12-22
• Study First Posted: 2021-12-27
• Study Start: 2022-11-01
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-21
• Last Update Posted: 2025-05-22
• Primary Completion: 2032-08-21
• Study Completion: 2033-09-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 121

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort A1: ALK-positive (durvalumab arm)	Durvalumab	Participants will receive 1500 mg of intravenous (IV) durvalumab every 4 weeks until completion of treatment period (1 year) or until disease progression, unacceptable toxicity, patient or physician decision to discontinue, or death, whichever occurs first
Cohort A1: ALK-Positive (alectinib arm)	Alectinib	Participants will receive alectinib 600 mg orally twice daily until completion of treatment period (3 years), or until disease progression, unacceptable toxicity, patient or physician decision to discontinue, or death, whichever occurs first
Cohort A2: ROS 1-positive (entrectinib arm)	Entrectinib	Participants will receive entrectinib 600 mg orally once daily until completion of treatment period (3 years), or until disease progression, unacceptable toxicity, patient or physician decision to discontinue, or death, whichever occurs first. Cohort A2 has been closed to enrollment.
Cohort A2: ROS 1-positive (durvalumab arm)	Durvalumab	Participants will receive 1500 mg of IV durvalumab every 4 weeks until completion of treatment period (1 year) or until disease progression, unacceptable toxicity, patient or physician decision to discontinue, or death, whichever occurs first Cohort A2 has been closed to enrollment.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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)
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)
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
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)
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)
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
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)
Overall survival (OS)	From randomization to death from any cause (up to 5 years)
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)
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)
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
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
Percentage of participants with adverse events (AEs)	Up to 3 years

Trial Locations

Locations (179)

RedSalud Vitacura; 🇨🇱 Santiago, Chile

Southern California Kaiser Permanente; 🇺🇸 Los Angeles, California, United States

Rocky Mountain Cancer Centers - Lone Tree; 🇺🇸 Lone Tree, Colorado, United States

Mount Sinai Medical Center; 🇺🇸 Miami Beach, Florida, United States

Centro de Estudios Clínicos SAGA; 🇨🇱 Santiago, Chile

University of South Alabama; 🇺🇸 Mobile, Alabama, United States

University Of Michigan; 🇺🇸 Ann Arbor, Michigan, United States

Oregon Health Sciences Uni; 🇺🇸 Portland, Oregon, United States

Northwest Cancer Specialists, P.C.; 🇺🇸 Tigard, Oregon, United States

Hillman Cancer Center; 🇺🇸 Pittsburgh, Pennsylvania, United States

Thompson Cancer Survival Center; 🇺🇸 Knoxville, Tennessee, United States

Baptist Cancer Center; 🇺🇸 Memphis, Tennessee, United States

The University of Texas MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Mays Cancer Center, UT Health San Antonio; 🇺🇸 San Antonio, Texas, United States

Virginia Cancer Specialists (Fairfax) - USOR; 🇺🇸 Fairfax, Virginia, United States

Lifehouse; 🇦🇺 Camperdown, New South Wales, Australia

GenesisCare North Shore; 🇦🇺 St Leonards, New South Wales, Australia

Westmead Hospital; 🇦🇺 Westmead, New South Wales, Australia

Peter MacCallum Cancer Centre; 🇦🇺 Melbourne, Victoria, Australia

One Clinical Research; 🇦🇺 Nedlands, Western Australia, Australia

GHdC Site Les Viviers; 🇧🇪 Charleroi, Belgium

UZ Gent; 🇧🇪 Gent, Belgium

Hospital Sao Rafael - HSR; 🇧🇷 Salvador, Bahia, Brazil

OrlandiOncología; 🇨🇱 Santiago, Chile

Crio - Centro Regional Integrado de Oncologia; 🇧🇷 Fortaleza, Ceará, Brazil

Instituto do Cancer Brasil; 🇧🇷 Tres Lagoas, Mato Grosso Do Sul, Brazil

Oncocentro Belo Horizonte; 🇧🇷 Belo Horizonte, Minas Gerais, Brazil

COT - Centro Oncologico do Triangulo; 🇧🇷 Uberlandia, Minas Gerais, Brazil

Santa Casa de Misericordia de Porto Alegre; 🇧🇷 Porto Alegre, Rio Grande Do Sul, Brazil

Hospital Nossa Senhora da Conceicao; 🇧🇷 Porto Alegre, Rio Grande Do Sul, Brazil

Clínica de Oncologia Reichow; 🇧🇷 Blumenau, Santa Catarina, Brazil

Hospital de Cancer de Barretos; 🇧🇷 Barretos, São Paulo, Brazil

Instituto do Cancer do Estado de Sao Paulo - ICESP; 🇧🇷 Sao Paulo, São Paulo, Brazil

Oncoclinicas Rio de Janeiro S.A.; 🇧🇷 Rio de Janeiro, Brazil

Sunnybrook Health Sciences Centre; 🇨🇦 Toronto, Ontario, Canada

K2 Oncology; 🇨🇱 Providencia, Chile

James Lind Centro de Investigación Del Cáncer; 🇨🇱 Temuco, Chile

Beijing Cancer Hospital; 🇨🇳 Beijing, 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; 🇨🇳 Tianjing, China

Union Hospital Tongji Medical College Huazhong University of Science and Technology; 🇨🇳 Wuhan City, China

Shanxi Cancer Hospital; 🇨🇳 Xi'an, China

Clinica De La Costa; 🇨🇴 Barranquilla, Colombia

Fundación CTIC - Centro de Tratamiento e Investigación sobre Cáncer Luis Carlos Sarmiento Angulo; 🇨🇴 Bogota, D.C., Colombia

Hospital Universitario San Ignacio; 🇨🇴 Bogota, Colombia

Instituto Cancerología Medellin; 🇨🇴 Medellin, Colombia

Clinica CIMCA; 🇨🇷 San Jose, Costa Rica

ICIMED Instituto de Investigación en Ciencias Médicas; 🇨🇷 San José, Costa Rica

CHU Angers,Service de Pneumologie; 🇫🇷 Angers, France

Polyclinique Bordeaux Nord Aquitaine; 🇫🇷 Bordeaux, France

Hôpital Ambroise Paré - Boulogne-Billancourt; 🇫🇷 Boulogne Billancourt, France

Centre Francois Baclesse; 🇫🇷 Caen, France

Centre Leon Berard; 🇫🇷 Lyon, France

Hopital Nord; 🇫🇷 Marseille cedex 20, France

Hôpitaux D'Instruction Des Armees Begin; 🇫🇷 St Mande, France

CHU Strasbourg - Nouvel Hopital Civil; 🇫🇷 Strasbourg, France

Hia Sainte Anne; 🇫🇷 Toulon, France

CHU de Toulouse - Hôpital Larrey; 🇫🇷 Toulouse, France

Helios Klinikum Emil von Behring GmbH; 🇩🇪 Berlin, Germany

Klinikum Chemnitz gGmbH; 🇩🇪 Chemnitz, Germany

Klinikum Esslingen; 🇩🇪 Esslingen, Germany

Thoraxklinik Heidelberg gGmbH; 🇩🇪 Heidelberg, Germany

LMU Klinikum der Universität München, Medizinische Klinik und Poliklinik V, Campus Innenstadt; 🇩🇪 München, Germany

Universitätsklinikum Regensburg; 🇩🇪 Regensburg, Germany

Universitätsklinikum Würzburg; 🇩🇪 Würzburg, Germany

Queen Mary Hospital; 🇭🇰 Hong Kong, Hong Kong

Rajiv Gandhi Cancer Inst.&Research Center; 🇮🇳 New Delhi, Delhi, India

Medanta-The Medicity; 🇮🇳 Gurgaon, Haryana, India

Tata Memorial Hospital; 🇮🇳 Mumbai, Maharashtra, India

Apollo Gleneagles Hospital; 🇮🇳 Kolkata, WEST Bengal, India

Rambam Medical Center; 🇮🇱 Haifa, Israel

Rabin Medical Center-Beilinson Campus; 🇮🇱 Petach Tikva, Israel

IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola; 🇮🇹 Meldola, Emilia-Romagna, Italy

IRCCS Istituto Regina Elena (IFO); 🇮🇹 Roma, Lazio, Italy

Azienda Ospedaliera San Camillo Forlanini; 🇮🇹 Roma, Lazio, Italy

IRCCS A.O.U San MArtino - IST; 🇮🇹 Genova, Liguria, Italy

Asst Degli Spedali Civili Di Brescia; 🇮🇹 Brescia, Lombardia, Italy

Irccs Istituto Europeo di Oncologia (IEO); 🇮🇹 Milano, Lombardia, Italy

Asst Grande Ospedale Metropolitano Niguarda; 🇮🇹 Milano, Lombardia, Italy

A.O. Universitaria S. Luigi Gonzaga; 🇮🇹 Orbassano, Piemonte, Italy

IRCCS Giovanni Paolo II Istituto Oncologico; 🇮🇹 Bari, Puglia, Italy

Azienda Ospedaliero-Universitaria Careggi; 🇮🇹 Firenze, Toscana, Italy

IRCCS Istituto Oncologico Veneto (IOV); 🇮🇹 Padova, Veneto, Italy

Ospedale P. Pederzoli Casa di cura Privata; 🇮🇹 Peschiera Del Garda (VR), Veneto, Italy

Aichi Cancer Center Hospital; 🇯🇵 Aichi, Japan

Hirosaki University Hospital; 🇯🇵 Aomori, Japan

National Cancer Center East; 🇯🇵 Chiba, Japan

Shikoku Cancer Center; 🇯🇵 Ehime, Japan

NHO Kyushu Cancer Center; 🇯🇵 Fukuoka, Japan

Kurume University Hospital; 🇯🇵 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

Okayama University Hospital; 🇯🇵 Okayama, Japan

Kurashiki Central Hospital; 🇯🇵 Okayama, Japan

Kindai University Hospital; 🇯🇵 Osaka-sayama, Japan

Osaka City General Hospital; 🇯🇵 Osaka, Japan

Osaka International Cancer Institute; 🇯🇵 Osaka, Japan

NHO Kinki Chuo Chest Medical Center; 🇯🇵 Osaka, 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, Japan

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

Kangbuk Samsung Hospital; 🇰🇷 Seoul, Korea, Republic of

Asan Medical Center; 🇰🇷 Seoul, Korea, Republic of

Korea University Guro Hospital; 🇰🇷 Seoul, Korea, Republic of

Hospital Civil de Guadalajara Fray Antonio Alcalde; 🇲🇽 Guadalajara, Jalisco, Mexico

Clinstile S.A de C.V.; 🇲🇽 Mexico City, Mexico CITY (federal District), Mexico

Centro de Investigación Oncologica Galerias; 🇲🇽 Aguascalientes, Mexico

ARKE Estudios Clínicos S.A. de C.V.; 🇲🇽 Ciudad de México, Mexico

Maastricht University Medical Center; 🇳🇱 Maastricht, Netherlands

Auckland City Hospital, Cancer and Blood Research; 🇳🇿 Auckland, New Zealand

Oslo university hospital Radiumhospitalet; 🇳🇴 Oslo, Norway

Instytut Genetyki i Immunologii GENIM; 🇵🇱 Lublin, Poland

Warminsko-Mazurskie Centrum Chorób P?uc w Olsztynie; 🇵🇱 Olsztyn, Poland

Wielkopolskie Centrum Pulmonologii i Torakochirurgii w Poznaniu; 🇵🇱 Poznan, Poland

Dolno?l?skie Centrum Chorób P?uc we Wroc?awiu; 🇵🇱 Wroc?aw, Poland

University Clinical Centre of Serbia; 🇷🇸 Belgrade, Serbia

Hospital Medical Center Bezanijska kosa; 🇷🇸 Belgrade, Serbia

Univ Clinical Center Kragujevac; 🇷🇸 Kragujevac, Serbia

Institute for Pulmonary Diseases of Vojvodina; 🇷🇸 Sremska Kamenica, Serbia

National Cancer Centre; 🇸🇬 Singapore, Singapore

Tan Tock Seng Hospital; 🇸🇬 Singapore, Singapore

Complejo Hospitalario Universitario A Coruña (CHUAC); 🇪🇸 A Coruña, LA Coruna, Spain

Complejo Hospitalario Universitario Insular?Materno Infantil; 🇪🇸 Las Palmas de Gran Canaria, LAS Palmas, Spain

Hospital General Univ. de Alicante; 🇪🇸 Alicante, Spain

Hospital Universitari Vall d'Hebron; 🇪🇸 Barcelona, Spain

Hospital Ramon y Cajal; 🇪🇸 Madrid, Spain

Hospital Universitario 12 de Octubre; 🇪🇸 Madrid, Spain

Hospital Universitario La Paz; 🇪🇸 Madrid, Spain

Hospital Regional Universitario Carlos Haya; 🇪🇸 Malaga, Spain

Hospital Universitario Virgen del Rocio; 🇪🇸 Sevilla, Spain

Hospital Clínico Universitario de Valencia; 🇪🇸 Valencia, Spain

Sahlgrenska University Hospital; 🇸🇪 Göteborg, Sweden

Karolinska Universitetssjukhuset, Solna; 🇸🇪 Stockholm, Sweden

Taipei Medical University ?Shuang Ho Hospital; 🇨🇳 New Taipei City, Taiwan

National Cheng Kung Univ Hosp; 🇨🇳 Tainan, Taiwan

National Taiwan Uni Hospital; 🇨🇳 Taipei City, Taiwan

Taipei Veterans General Hospital; 🇨🇳 Taipei City, Taiwan

Taipei Medical University Hospital; 🇨🇳 Taipei, Taiwan

Taipei Municipal Wan Fang Hospital; 🇨🇳 Taipei, Taiwan

Chang Gung Memorial Hospital - Linkou; 🇨🇳 Taoyuan, Taiwan

Taichung Veterans General Hospital; 🇨🇳 Xitun Dist., Taiwan

Rajavithi Hospital; 🇹🇭 Bangkok, Thailand

Faculty of Med. Siriraj Hosp.; 🇹🇭 Bangkok, Thailand

Oncology Unit, Faculty of Medicine, Vajira Hospital; 🇹🇭 Dusit, Thailand

Songklanagarind Hospital; 🇹🇭 Songkhla, Thailand

Ataturk Sanatoryum Egitim Ve Arastirma Hastanesi; 🇹🇷 Ankara, Turkey

Gazi Uni Medical Faculty Hospital; 🇹🇷 Ankara, Turkey

Liv Hospital Ankara; 🇹🇷 Ankara, Turkey

Bakirkoy Dr. Sadi Konuk Egitim ve Arastirma Hastanesi, Tibbi Onkoloji; 🇹🇷 Bakirkoy / Istanbul, Turkey

Dicle University Faculty of Medicine; 🇹🇷 Diyarbakir, Turkey

Ataturk University Medical Faculty Yakutiye Research Hospital Medical Oncology Department; 🇹🇷 Erzurum, Turkey

Medipol University Medical Faculty; 🇹🇷 Istanbul, Turkey

Marmara Uni Faculty of Medicine; 🇹🇷 Istanbul, Turkey

Medikal Park Samsun; 🇹🇷 Samsun, Turkey

Medical Park Seyhan Hospital; 🇹🇷 Seyhan, Turkey

Birmingham Heartlands Hospital; 🇬🇧 Birmingham, United Kingdom

North Middlesex Hospital; 🇬🇧 Harlow, United Kingdom

Barts & London School of Med; 🇬🇧 London, United Kingdom

Royal Marsden Hospital; 🇬🇧 London, United Kingdom

Christie Hospital Nhs Trust; 🇬🇧 Manchester, United Kingdom