Non-Small Cell Lung CancerPhase 3HORIZON 1NCT05170204
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)
A Phase 3 study testing Alectinib, Entrectinib and Durvalumab in people with Non-Small Cell Lung Cancer, run by Hoffmann-La Roche at 45 sites in 19 countries.
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 (AJCC/UICC) NSCLC staging system. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-Small Cell Lung Cancer
- What is being tested?
- Alectinib, Entrectinib and Durvalumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 68 participants
- Where
- 45 sitesin 19 countries
- Study dates
- 1 Nov 2022to 16 Jun 2030
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
- 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
Who cannot join
- 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
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- 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
- 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
- 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
Trial locations and contacts
45 sites in 19 countries.
45 sites in 19 countries
Japan8 sites
NHO Kyushu Cancer Center
Fukuoka, 811-1395
Kurume University Hospital
Fukuoka, 830-0011
Kobe City Medical Center General Hospital
Hyōgo, 650-0047
Kagoshima University Hospital
Kagoshima, 890-8520
Kumamoto University Hospital
Kumamoto, 860-8556
Kindai University Hospital
Osaka, 590-0197
Juntendo University Hospital
Tokyo, 113-8431
The Cancer Institute Hospital of JFCR
Tokyo, 135-8550
South Korea6 sites
Kyungpook National University Chilgok Hospital
Daegu, 41404
Pusan National University Yangsan Hospital
Gyeongsangnam-do, 50612
Chonnam National University Hwasun Hospital
Jeollanam-do, 58128
Seoul National University Bundang Hospital
Seongnam-si, 13605
Asan Medical Center
Seoul, 05505
Korea University Guro Hospital
Seoul, 08308
China4 sites
Hunan Cancer Hospital
Changsha, 410013
Xinqiao Hospital of Third Military Medical University
Chongqing, 400037
Shandong Cancer Hospital
Jinan, 250117
Shanghai Pulmonary Hospital
Shanghai, 200433
Thailand4 sites
Rajavithi Hospital
Bangkok, 10400
Faculty of Med. Siriraj Hosp.
Bangkok, 10700
Oncology Unit, Faculty of Medicine, Vajira Hospital
Dusit, 10300
Songklanagarind Hospital
Songkhla, 90110
France3 sites
Centre Francois Baclesse
Caen, 14000
Centre Leon Berard
Lyon, 69008
Hopital Nord
Marseille, 13915
United States2 sites
Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
Northwest Cancer Specialists, P.C.
Tigard, Oregon, 97223
Australia2 sites
Peter MacCallum Cancer Centre
Melbourne, Victoria, 3000
One Clinical Research
Nedlands, Western Australia, 6009
Brazil2 sites
Hospital de Cancer de Barretos
Barretos, São Paulo, 14784-400
Instituto do Cancer do Estado de Sao Paulo - ICESP
São Paulo, São Paulo, 01246-000
Colombia2 sites
Hospital Universitario San Ignacio
Bogotá, 000472
Fundación CTIC - Centro de Tratamiento e Investigación sobre Cáncer Luis Carlos Sarmiento Angulo
Bogota, D.C., 110131
Italy2 sites
IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola
Meldola, Emilia-Romagna, 47014
Asst Grande Ospedale Metropolitano Niguarda
Milan, Lombardy, 20162
Sweden2 sites
Sahlgrenska University Hospital
Gothenburg, 413 45
Karolinska Universitetssjukhuset, Solna
Stockholm, 171 76
Mexico1 site
Hospital Civil de Guadalajara Fray Antonio Alcalde
Guadalajara, Jalisco, 44280
About this study
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
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
- Being tested
- Alectinib, Entrectinib, Durvalumab
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AlectinibDrug
Also called RO5424802; Alecensa®
Participants will receive oral alectinib twice daily with food.
EntrectinibDrug
Also called RO7102122; Rozlytrek®
Participants will receive oral entrectinib once daily, with or without food.
DurvalumabDrug
Also called IMFINZI®
Participants will receive durvalumab, IV Q4W.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: 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. Receives: 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. Receives: Drug: Durvalumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 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
Measured: 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
Measured: 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
Measured: Up to 3 years
PFS, as Determined by the Investigator per RECIST v1.1
Measured: 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
Measured: From the first documented CR or PR to the first documented disease progression or death, whichever occurs first (up to 3 years)
ORR, as Determined by BICR per RECIST v1.1
Measured: Up to 3 years
DOR, as Determined by BICR per RECIST v1.1
Measured: From the first documented CR or PR to the first documented disease progression or death, whichever occurs first (up to 3 years)
Overall Survival (OS)
Measured: From randomization to death from any cause (up to 5 years)
Time to CNS Progression, as Determined by the Investigator per RECIST v1.1
Measured: From randomization to the first occurrence of disease progression in the CNS (up to 3 years)
DMFS, as Determined by the Investigator per RECIST v1.1
Measured: From randomization to the first occurrence of distant metastasis or death, whichever occurs first (up to 3 years)
Time-to-confirmed Deterioration (TTCD), as Measured Using the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (EORTC QLQ-C30) in Physical and Role Functioning Scales
Measured: 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)
TTCD, as Measured Using the EORTC QLQ - Lung Cancer 13-item Questionnaire (LC13) in Cough, Chest Pain and Dyspnea Symptom Scales
Measured: 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 EORTC QLQ-C30 Physical Functioning and Role Functioning Scales
Measured: At 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
Measured: At 5, 11, and 17 months
Percentage of Participants With Adverse Events (AEs)
Measured: Up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Dec 2021
- Study start1 Nov 2022
- Primary completion19 Jan 2027 (estimated)
- Study completion16 Jun 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-Small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 68 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05170204
- Sponsor's protocol ID
- BO42777
- Other IDs
- 2023-503920-14-00, 2023
- Acronym
- HORIZON 1
- Status last verified
- Oct 2026
- First submitted
- 22 Dec 2021
- Last updated
- 2 Nov 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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
Study at a glance
From the registry record, last updated by the sponsor on 2 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05170204
- Acronym / sponsor ID
- HORIZON 1 / BO42777
- Conditions
- Non-Small Cell Lung Cancer
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 68 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- 1 Nov 2022 (actual)
- Primary completion
- 19 Jan 2027 (estimated)
- Study completion
- 16 Jun 2030 (estimated)
- First posted
- 27 Dec 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Cohort A1: Anaplastic Lymphoma Kinase (ALK)-positive (Alectinib Arm) | Experimental | Drug: AlectinibParticipants 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 |
| Cohort A1: ALK-positive (Durvalumab Arm) | Active comparator | Drug: DurvalumabParticipants 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 |
| Cohort A2: ROS Proto-oncogene 1 (ROS 1)-positive (Entrectinib Arm) | Experimental | Drug: EntrectinibParticipants 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. |
| Cohort A2: ROS 1-positive (Durvalumab Arm) | Active comparator | Drug: DurvalumabParticipants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- 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)
Key exclusion criteria (53 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AlectinibAlso: RO5424802; Alecensa®Participants will receive oral alectinib twice daily with food. | Drug | Cohort A1: Anaplastic Lymphoma Kinase (ALK)-positive (Alectinib Arm) |
| EntrectinibAlso: RO7102122; Rozlytrek®Participants will receive oral entrectinib once daily, with or without food. | Drug | Cohort A2: ROS Proto-oncogene 1 (ROS 1)-positive (Entrectinib Arm) |
| DurvalumabAlso: IMFINZI®Participants will receive durvalumab, IV Q4W. | Drug | Cohort A1: ALK-positive (Durvalumab Arm), Cohort A2: ROS 1-positive (Durvalumab Arm) |
Primary outcome
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)
Time frame: From randomization to the first documented disease progression or death from any cause, whichever occurs first (up to 3 years)
15 secondary outcomes
Time to Central Nervous System (CNS) Progression, as Determined by BICR per RECIST v1.1
Time frame: 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
Time frame: 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
Time frame: Up to 3 years
PFS, as Determined by the Investigator per RECIST v1.1
Time frame: 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
Time frame: From the first documented CR or PR to the first documented disease progression or death, whichever occurs first (up to 3 years)
ORR, as Determined by BICR per RECIST v1.1
Time frame: Up to 3 years
DOR, as Determined by BICR per RECIST v1.1
Time frame: From the first documented CR or PR to the first documented disease progression or death, whichever occurs first (up to 3 years)
Overall Survival (OS)
Time frame: From randomization to death from any cause (up to 5 years)
Time to CNS Progression, as Determined by the Investigator per RECIST v1.1
Time frame: From randomization to the first occurrence of disease progression in the CNS (up to 3 years)
DMFS, as Determined by the Investigator per RECIST v1.1
Time frame: From randomization to the first occurrence of distant metastasis or death, whichever occurs first (up to 3 years)
Time-to-confirmed Deterioration (TTCD), as Measured Using the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (EORTC QLQ-C30) in Physical and Role Functioning Scales
Time frame: 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)
TTCD, as Measured Using the EORTC QLQ - Lung Cancer 13-item Questionnaire (LC13) in Cough, Chest Pain and Dyspnea Symptom Scales
Time frame: 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 EORTC QLQ-C30 Physical Functioning and Role Functioning Scales
Time frame: At 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
Time frame: At 5, 11, and 17 months
Percentage of Participants With Adverse Events (AEs)
Time frame: Up to 3 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Nov 2026.
- Individual participant dataSharing planned: Yes. 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
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trials study director
Hoffmann-La Roche
45 sites in 19 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Alectinib, Entrectinib and Durvalumab in people with Non-Small Cell Lung Cancer, run by Hoffmann-La Roche at 45 sites in 19 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 53 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 2 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 45 sites in Japan, South Korea, China, Thailand, France and 14 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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) (time frame: From randomization to the first documented disease progression or death from any cause, whichever occurs first (up to 3 years)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Nov 2026.