Non-Small Cell Lung Cancer (NSCLC) MedDRA version: 23.1 Level: LLT Classification code 10084713 Term: Tumor System Organ Class: 100000004864
Conditions
Sponsors
F. Hoffmann La Roche Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Age >=18 years Body weight >=30 kg Whole-body positron emission tomography/computed tomography scan (PET/CT) 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 (Version 8, American Joint Committee on Cancer/Union for International Cancer Control NSCLC staging system (Amin et al. 2017). 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 Documented tumor PD-L1 status 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, during the treatment period and for at least 90 days after the final dose of alectinib or durvalumab (Cohort A1 only) For women of childbearing potential: Agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception, and agreement to refrain from donating eggs, during the treatment period, and for at least 35 days after the final dose of entrectinib, or 90 days after the final dose of durvalumab (Cohort A2 only) For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception, and agreement to refrain from donating eggs, during the treatment period, and for at least 14 days after the final dose of pralsetinib, or at least 90 days after the final dose of durvalumab (Cohort A3 only) For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agreement to refrain from donating sperm during the treatment period and for least 90 days after the final dose of alectinib or durvalumab (Cohort A1 only) For men: Agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom plus an additional contraception method, and agreement to refrain from donating sperms, during the treatment period and for at least 3 months after the final dose of entrectinib or final dose of durvalumab Cohort A2 only) For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm, during the treatment period and for at least 7 days after the final dose of pralsetinib and at least 90 days after the final dose of durvalumab (Cohort A3 only) Ability to swallow entrectinib intact, without chewing, crushing, or opening the capsules (Cohort A2 only) Confirmed availability of a representative formalin-fixed, paraffin-embedded (FFPE) tumor specimen Documented ALK fusion positivity (Cohort A1 only) Documented ROS1 fusion positivity (Cohort A2 only) Documented RET fusion positivity (Cohort A3 only Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 7
Exclusion criteria
Exclusion criteria: Any history of previous NSCLC and/or any history of prior treatment for NSCLC Any evidence of Stage IV disease If pleural effusion is present the following criteria must be met to exclude malignant involvement (T4 disease): When pleural fluid is visible on both the computed tomography scan & chest X-ray, a pleuracentesis is required to confirm that the pleural fluid is cytologically negative. Patients with exudative pleural effusions are excluded regardless of cytology. Patients with effusions that are minimal (ie not visible on chest X-ray) that are too small to safely tap are eligible 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 (Cohort A1) 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 Positive hepatitis B surface antigen test at screening Patients known to be positive for hepatitis C virus antibody HIV infection, patients are excluded if HIV is not adequately controlled(specific criteria apply) Known active tuberculosis Presence of clinically symptomatic interstitial lung disease or interstitial pneumonitis, including radiation pneumonitis (Cohorts A1, A3) Grade = 2 pneumonitis from prior cCRT or sCRT Symptomatic bradycardia(Cohort A1,A2) Significant cardiovascular disease within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina Left ventricular ejection fraction less than or equal to 50% observed during the screening for the study (Cohort A2) Any gastrointestinal (GI) disorder that may affect absorption of oral medications 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 History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on the screening chest CT scan History of malignancy other than NSCLC within 5 years prior to screening 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 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 systemic immunostimulatory agents Treatment with live, attenuated vaccine Treatment with investigational therapy within 28 days prior to initiation of study treatment Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment Treatment with systemic immunosuppressive medication Prior treatment with ALK inhibitors (Cohort A1) Prior treatment with ROS1 inhibitors (Cohort A2) Prior treatment with RET inhibitors (Cohort A3) Prior treatment with CD137 agonists or immune checkpoint blockade therapies Prior allogeneic stem cell or solid organ transplantation History of hypersensitivity to alectinib, durvalumab, or any of their excipients (Cohort A1) History of hypersensitivi
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of study treatment (alectinib or entrectinib or pralsetinib) compared with durvalumab in patients with biomarker-selected, locally advanced, unresectable, Stage III NSCLC who have received concurrent chemoradiotherapy (cCRT) or sequential chemoradiotherapy (sCRT) and have not had radiographic disease progression;Secondary Objective: To evaluate the health-related quality of life of patients with biomarker-selected locally advanced, unresectable, Stage III NSCLC who have received cCRT or sCRT and have not had radiographic disease progression in the study treatment arm compared with in the durvalumab arm To evaluate the safety and tolerability of study treatment compared with durvalumab in patients with biomarker selected, locally advanced, unresectable, Stage III NSCLC who have received cCRT or sCRT and have not had radiographic disease progression ;Primary end point(s): 1.Progression-free survival (PFS), as determined by Blinded independent central review (BICR) per RECIST v1.1 ;Timepoint(s) of evaluation of this end point: 1. Up to approximately 5 years | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. PFS, defined as the time 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 2. Time to central nervous system (CNS) progression, as determined by BICR and investigator per RECIST v1.1 3. Distant metastasis-free survival (DMFS), s determined by BICR per RECIST v1.1 4. Objective response rate (ORR), as determined by BICR and investigator per RECIST v1.1 5. Duration of response (DOR), as determined by BICR and investigator per RECIST v1.1 6. Overall survival (OS) 7. Time-to-confirmed deterioration (TTCD), in the following patient-reported scales and lung cancer symptoms: Physical functioning, Role functioning, Cough, Chest pain, Dyspnea 8. Change from baseline score as measured through the use of the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) at 5, 11, and 17 months in the following patient-reported scales and lung cancer symptoms: Physical functioning, Role functioning, Cough, Chest pain, Dyspnea 9. Incidence, type, and severity of adverse events according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) 10. Changes in vital signs, physical findings, and clinical laboratory results during and following administration of protocol-specified investigational medicinal products (IMPs) ;Timepoint(s) of evaluation of this end point: 1-7. Up to approximately 5 years 8. Baseline to 5 years 9. Up to approximately 5 years 10. Baseline to 5 years | — |
Countries
Australia, Belgium, Brazil, Canada, Chile, China, Colombia, Costa Rica, France, Germany, Hong Kong, India, Italy, Japan, Korea, Republic of, Netherlands, New Zealand, Norway, Poland, Serbia, Singapore, Spain, Sweden, Taiwan, Thailand, Turkey, United Kingdom, United States
Contacts
Public ContactTrial Information Support Line-TISL
F. Hoffmann La Roche Ltd.
Outcome results
None listed