Lung Cancer Clinical Trial

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)

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.

View Eligibility Criteria

Eligibility Criteria

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

Inclusion criteria specific to Cohort A3:

Documented RET 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 RET fusion test on tumor tissue performed in a Clinical Laboratory Improvement Amendments certified or equivalent laboratory

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

Exclusion criteria specific to Cohort A3:

Participant has significant cardiovascular disease, as evidenced by any of the following conditions: QT interval corrected through the use of Fridericia's formula (QTcF) > 480 ms; history of prolonged QT syndrome or torsades de pointes; familial history of prolonged QT syndrome
Total serum phosphorous > 5.5 mg/dL
Participant has clinically significant, uncontrolled, cardiovascular disease, including Grade III or IV congestive heart failure according to the New York Heart Association classification; myocardial infarction or unstable angina within the previous 6 months, uncontrolled hypertension, or clinically significant, uncontrolled arrhythmias, including bradyarrhythmias that may cause QT prolongation (e.g., Type II second-degree or third-degree heart block)
Treatment with a prohibited medication (i.e., strong inhibitors of CYP3A4, strong inducers of CYP3A4, combined P-glycoprotein and strong CYP3A4 inhibitors) or herbal remedy, within 2 weeks prior to the start of study drug administration
Participant with a serious infection requiring IV or systemic antibiotics within 7 days prior to initiation of study treatment, or any active infection that, in the opinion of the investigator, could impact patient's safety. In the setting of a pandemic or epidemic, screening for active infections should be considered according to local or institutional guidelines or applicable guidelines (e.g., NCCN, ESMO)
Participant has an active, uncontrolled infection (viral, bacterial, or fungal)
Prior treatment with RET inhibitors
History of hypersensitivity to pralsetinib, durvalumab, or any of their excipients
Inability to swallow oral study drug
Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within 2 weeks after the final dose of pralsetinib or 3 months after the final dose of durvalumab

Study is for people with:

Lung Cancer

Phase:

Phase 3

Estimated Enrollment:

320

Study ID:

NCT05170204

Recruitment Status:

Recruiting

Sponsor:

Hoffmann-La Roche

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There are 22 Locations for this study

See Locations Near You

Thompson Cancer Survival Center
Knoxville Tennessee, 37916, United States
Virginia Cancer Specialists (Fairfax) - USOR
Fairfax Virginia, 22031, United States
One Clinical Research
Nedlands Western Australia, 6009, Australia
Shanghai Pulmonary Hospital
Shanghai , 20043, China
Fundacion Cardioinfantil
Bogota , , Colombia
Clinica CIMCA
San José , 10103, Costa Rica
ICIMED Instituto de Investigación en Ciencias Médicas
San José , 10108, Costa Rica
Queen Mary Hospital; Dept. of Clinical Oncology
Hong Kong , , Hong Kong
Kurume University Hospital
Fukuoka , 830-0, Japan
National Hospital Organization Himeji Medical Center
Hyogo , 670-8, Japan
Kagoshima University Hospital
Kagoshima , 890-8, Japan
Kumamoto University Hospital
Kumamoto , 860-8, Japan
Sendai Kousei Hospital
Miyagi , 980-0, Japan
Nara Medical University Hospital
Nara , 634-8, Japan
Okayama University Hospital
Okayama , 700-8, Japan
Kurashiki Central Hospital
Okayama , 710-8, Japan
Shizuoka Cancer Center
Shizuoka , 411-8, Japan
The Cancer Institute Hospital of JFCR
Tokyo , 135-8, Japan
Tottori University Hospital
Tottori , 683-8, Japan
Kyungpook National University Chilgok Hospital
Daegu , 41404, Korea, Republic of
Seoul National University Bundang Hospital
Seongnam-si , 13605, Korea, Republic of
Korea University Guro Hospital
Seoul , 08308, Korea, Republic of
Narod.Inst.Onkol. im. M.Sklodowskiej - Curie-Panst.Inst.Bad; Klinika Nowot.Pluca i Klatki Piers
Warszawa , 02-78, Poland
Songklanagarind Hospital; Department of Internal Medicine, Division of Respiratory
Songkhla , 90110, Thailand

How clear is this clinincal trial information?

Study is for people with:

Lung Cancer

Phase:

Phase 3

Estimated Enrollment:

320

Study ID:

NCT05170204

Recruitment Status:

Recruiting

Sponsor:


Hoffmann-La Roche

How clear is this clinincal trial information?

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