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)

Study 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.

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Key things to know

Main goalTreatment

This describes the study’s primary purpose.

What is being studiedAlectinib and Entrectinib

Plus 1 other study approaches.

Who it may be forNon-small cell lung cancer (NSCLC) · Early-stage or resectable · Locally advanced

These are broad labels—not an eligibility decision.

Checked against the public recordLast updated Aug 5, 2026 · Source: ClinicalTrials.gov

Is enrollment open?Active Not Recruiting

The study is underway but is not accepting new participants.

What kind of study?Phase 3

Interventional

Where is it offered?45 U.S. locations

Locations may change over time.

Who runs it?Hoffmann-La Roche

Study sponsor

Study overview

What this study is about

Purpose: Treatment
Study type: Interventional
Phase: Phase 3
Sponsor: Hoffmann-La Roche
Interventions being studied: Drug: Alectinib; Drug: Entrectinib; Drug: Durvalumab

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How this study is categorized

These labels come from structured fields and exact terms in the public record.

Cancer type

Non-small cell lung cancer (NSCLC)→

Disease setting

Early-stage or resectable→Locally advanced→

Treatment approach

Immunotherapy→Targeted therapy→

Public criteria

Who may be able to participate

The sponsor separates these requirements into two groups. You do not need to interpret them alone—use them to guide a conversation with the study team.

Requirements people may need to meetInclusion criteria

(All Cohorts):
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 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 prior tissue-based testing performed in an accredited or certified 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

Reasons someone may not be able to joinExclusion criteria

(All Cohorts):
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
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

Important: This is the sponsor’s public criteria, not a determination of eligibility. The study team must review your individual situation.

Study sites

U.S. locations

Northwest Cancer Specialists, P.C.Tigard, Oregon
Hillman Cancer CenterPittsburgh, Pennsylvania
Peter MacCallum Cancer CentreMelbourne, Victoria
One Clinical ResearchNedlands, Western Australia
UZ GentGhent
Hospital de Cancer de BarretosBarretos, São Paulo
Instituto do Cancer do Estado de Sao Paulo - ICESPSão Paulo, São Paulo
RedSalud VitacuraSantiago
Hunan Cancer HospitalChangsha
Xinqiao Hospital of Third Military Medical UniversityChongqing
Shandong Cancer HospitalJinan
Shanghai Pulmonary HospitalShanghai

Source and freshness
Processed from ClinicalTrials.gov. Last public update: Aug 5, 2026. Always confirm current availability with the study team.

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