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)

NCT05170204 | Active Not Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: BO427772023-503920-14-00
• Study Type: interventional
• Target: 68
• Locations: 19 countries
• Sites: 45

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 (AJCC/UICC) NSCLC staging system.

Conditions

Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival (PFS), as Determined by Blinded Independent Central Review (BICR) per Response Evaluation Criterial in Solid Tumors Version 1.1 (RECIST V1.1)

  From randomization to the first documented disease progression or death from any cause, whichever occurs first (up to 3 years)

Secondary Outcomes (15)

• Time to Central Nervous System (CNS) Progression, as Determined by BICR per RECIST v1.1

  From randomization to the first occurrence of disease progression in the CNS (up to 3 years)

• Distant Metastasis-free Survival (DMFS), as Determined by BICR per RECIST v1.1

  From randomization to the first occurrence of distant metastasis or death, whichever occurs first (up to 3 years)

• Objective Response Rate (ORR), as Determined by the Investigator per RECIST v1.1

  Up to 3 years

• PFS, as Determined by the Investigator per RECIST v1.1

  From randomization to the first documented disease progression or death from any cause, whichever occurs first (up to 3 years)

• Duration of response (DOR), as Determined by the Investigator per RECIST v1.1

  From the first documented CR or PR to the first documented disease progression or death, whichever occurs first (up to 3 years)

Study Arms (4)

Cohort A1: Anaplastic Lymphoma Kinase (ALK)-positive (Alectinib Arm)

EXPERIMENTAL

Participants will receive alectinib 600 milligrams (mg) orally twice daily until completion of treatment period (3 years), or until disease progression, unacceptable toxicity, participant or physician decision to discontinue, or death, whichever occurs first

Drug: Alectinib

Cohort A1: ALK-positive (Durvalumab Arm)

ACTIVE COMPARATOR

Participants will receive 1500 mg of intravenous (IV) durvalumab every 4 weeks (Q4W) until completion of treatment period (1 year) or until disease progression, unacceptable toxicity, participant or physician decision to discontinue, or death, whichever occurs first

Drug: Durvalumab

Cohort A2: ROS Proto-oncogene 1 (ROS 1)-positive (Entrectinib Arm)

EXPERIMENTAL

Participants will receive entrectinib 600 mg orally once daily until completion of treatment period (3 years), or until disease progression, unacceptable toxicity, participant or physician decision to discontinue, or death, whichever occurs first. Cohort A2 has been closed to enrollment.

Drug: Entrectinib

Cohort A2: ROS 1-positive (Durvalumab Arm)

ACTIVE COMPARATOR

Participants will receive 1500 mg of IV durvalumab Q4W until completion of treatment period (1 year) or until disease progression, unacceptable toxicity, participant or physician decision to discontinue, or death, whichever occurs first Cohort A2 has been closed to enrollment.

Drug: Durvalumab

Interventions

Alectinib DRUG

Participants will receive oral alectinib twice daily with food.

Also known as: RO5424802; Alecensa®

Cohort A1: Anaplastic Lymphoma Kinase (ALK)-positive (Alectinib Arm)

Entrectinib DRUG

Participants will receive oral entrectinib once daily, with or without food.

Also known as: RO7102122; Rozlytrek®

Cohort A2: ROS Proto-oncogene 1 (ROS 1)-positive (Entrectinib Arm)

Durvalumab DRUG

Participants will receive durvalumab, IV Q4W.

Also known as: IMFINZI®

Cohort A1: ALK-positive (Durvalumab Arm); Cohort A2: ROS 1-positive (Durvalumab Arm)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Body weight ≥ 30 kilograms (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 for Cohort A2 (ROS1 positive) and 50 days for Cohort A1 (ALK positive) of the first dose of concurrent chemoradiotherapy (cCRT) or sequential chemoradiotherapy (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 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
• Tumor programmed death-ligand 1 (PD-L1) status (TC score \< 1% vs. ≥ 1% vs. unknown) as determined using the VENTANA PD-L1 IHC SP263 assay (preferred) or the Dako PD-L1 IHC 22C3 pharmDx assay
• Eastern Cooperative Oncology Group (ECOG) 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
• 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 prior tissue-based testing performed in an accredited or certified laboratory

You may not qualify if:

• Any history of previous NSCLC and/or any history of prior treatment for NSCLC (participants 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 epidermal growth factor receptor (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 ribonucleic acid (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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (45)

Northwest Cancer Specialists, P.C.

Tigard, Oregon, 97223, United States

Location

Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

Location

One Clinical Research

Nedlands, Western Australia, 6009, Australia

Location

UZ Gent

Ghent, 9000, Belgium

Location

Hospital de Cancer de Barretos

Barretos, São Paulo, 14784-400, Brazil

Location

Instituto do Cancer do Estado de Sao Paulo - ICESP

São Paulo, São Paulo, 01246-000, Brazil

Location

RedSalud Vitacura

Santiago, Chile

Location

Hunan Cancer Hospital

Changsha, 410013, China

Location

Xinqiao Hospital of Third Military Medical University

Chongqing, 400037, China

Location

Shandong Cancer Hospital

Jinan, 250117, China

Location

Shanghai Pulmonary Hospital

Shanghai, 200433, China

Location

Fundación CTIC - Centro de Tratamiento e Investigación sobre Cáncer Luis Carlos Sarmiento Angulo

Bogota, D.C., 110131, Colombia

Location

Hospital Universitario San Ignacio

Bogotá, 000472, Colombia

Location

Centre Francois Baclesse

Caen, 14000, France

Location

Centre Leon Berard

Lyon, 69008, France

Location

Hopital Nord

Marseille, 13915, France

Location

Helios Klinikum Emil von Behring GmbH

Berlin, 14165, Germany

Location

IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola

Meldola, Emilia-Romagna, 47014, Italy

Location

Asst Grande Ospedale Metropolitano Niguarda

Milan, Lombardy, 20162, Italy

Location

NHO Kyushu Cancer Center

Fukuoka, 811-1395, Japan

Location

Kurume University Hospital

Fukuoka, 830-0011, Japan

Location

Kobe City Medical Center General Hospital

Hyōgo, 650-0047, Japan

Location

Kagoshima University Hospital

Kagoshima, 890-8520, Japan

Location

Kumamoto University Hospital

Kumamoto, 860-8556, Japan

Location

Kindai University Hospital

Ōsaka-sayama, 589-8511, Japan

Location

Juntendo University Hospital

Tokyo, 113-8431, Japan

Location

The Cancer Institute Hospital of JFCR

Tokyo, 135-8550, Japan

Location

Hospital Civil de Guadalajara Fray Antonio Alcalde

Guadalajara, Jalisco, 44280, Mexico

Location

Dolno?l?skie Centrum Chorób P?uc we Wroc?awiu

Wroc?aw, 53-439, Poland

Location

National Cancer Centre

Singapore, 168583, Singapore

Location

Kyungpook National University Chilgok Hospital

Daegu, 41404, South Korea

Location

Pusan National University Yangsan Hospital

Gyeongsangnam-do, 50612, South Korea

Location

Chonnam National University Hwasun Hospital

Jeollanam-do, 58128, South Korea

Location

Seoul National University Bundang Hospital

Seongnam-si, 13605, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Korea University Guro Hospital

Seoul, 08308, South Korea

Location

Sahlgrenska University Hospital

Gothenburg, 413 45, Sweden

Location

Karolinska Universitetssjukhuset, Solna

Stockholm, 171 76, Sweden

Location

Taichung Veterans General Hospital

Taichung, 40705, Taiwan

Location

Rajavithi Hospital

Bangkok, 10400, Thailand

Location

Faculty of Med. Siriraj Hosp.

Bangkok, 10700, Thailand

Location

Oncology Unit, Faculty of Medicine, Vajira Hospital

Dusit, 10300, Thailand

Location

Songklanagarind Hospital

Songkhla, 90110, Thailand

Location

Christie Hospital Nhs Trust

Manchester, M2O 4BX, United Kingdom

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

alectinib; entrectinib; durvalumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 22, 2021
• First Posted: December 27, 2021
• Study Start: November 1, 2022
• Primary Completion (Estimated): June 16, 2030
• Study Completion (Estimated): June 16, 2030
• Last Updated: May 6, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share

Locations

CN (4); TH (4); SG (1); GB (1); CL (1); CO (2); ME (1); PL (1); FR (3); IT (2); US (2); BE (1); JP (8); BR (2); TW (1); AU (2); KR (6); SE (2); DE (1)