Non-small cell lung cancer (NSCLC) MedDRA version: 21.1 Level: PT Classification code 10029519 Term: Non-small cell lung cancer stage III System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Age>= 18 years - Eastern Cooperative Oncology Group Performance Status of 0 or 1 - Histologically or cytologically documented NSCLC with locally advanced unresectable Stage III NSCLC of either squamous or nonsquamous histology - Whole-body positron emission tomography (PET)-CT scan for the purposes of staging, performed prior and within 42 days of the first dose of concurrent chemoradiotherapy (cCRT) - At least two prior cycles of platinum-based chemotherapy administered concurrently with RT, which must be completed within 1 to 42 days prior to randomization in the study (one cycle of cCRT is defined as 21 or 28 days) - The RT component in the cCRT must have been at a total dose of radiation of 60 Gy±10% (54 Gy to 66 Gy) administered by intensitymodulated radiotherapy (preferred) or 3D-conforming technique - No progression during or following concurrent platinum-based CRT - A known programmed death ligand 1 (PD-L1) result, as determined by the investigational Ventana PD-L1 (SP263) CDx assay and documented by means of central testing of a representative tumor tissue, in either a previously obtained archival tumor tissue or fresh tissue obtained from a biopsy collected prior to the first dose of cCRT - Adequate hematologic and end-organ function. 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 353 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 455
Exclusion criteria
Exclusion criteria: - Any history of prior NSCLC and/or any history of prior treatment for NSCLC (patients must be newly diagnosed with unresectable Stage III disease) - NSCLC known to have a mutation in the epidermal growth factor mutation and/or an anaplastic lymphoma kinase (ALK) fusion oncogene - Any evidence of Stage IV disease - Treatment with sequential CRT for locally advanced NSCLC - Patients with locally advanced NSCLC who have progressed during or after the definitive cCRT prior to randomization - Any Grade > 2 unresolved toxicity from previous CRT - Grade >=2 pneumonitis from prior CRT - Active or history of autoimmune disease or immune deficiency, history of idiopathic pulmonary fibrosis, organizing pneumonia - History of malignancy other than NSCLC within 5 years prior to screening - 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, or any active infection that, in the opinion of the investigator, could impact patient safety - Prior allogeneic stem cell or solid organ transplantation - Active Epstein-Barr virus (EBV) infection or known or suspected chronic active EBV infection at screening - Treatment with investigational therapy within 28 days prior to initiation of study treatment - Prior treatment with CD137 agonists or immune checkpoint blockade therapies - 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 - Current treatment with anti-viral therapy for hepatitis B virus or hepatitis C virus - Active EBV infection or known or suspected chronic active EBV infection at Screening - Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-cytotoxic T lymphocyte-associated protein 4, anti-T-cell immunoreceptor with Ig and ITIM domains, anti-PD-1, and anti-PD-L1 therapeutic antibodies - Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor-[anti TNFalpha] agents) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during study treatment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: ? To evaluate the efficacy of tiragolumab plus atezolizumab compared with durvalumab in the programmed death ligand 1 positive analysis set (PPAS) on the basis of PFS, as assessed by an IRF. ? To evaluate the efficacy of tiragolumab plus atezolizumab compared with durvalumab in the full analysis set (FAS) on the basis of progression-free survival (PFS), as assessed by an independent review facility (IRF);Secondary Objective: ? To evaluate the efficacy of tiragolumab plus atezolizumab compared with durvalumab in the PPAS and FAS on the basis of overall survival (OS), PFS as assessed by investigator, confirmed objective response rate (ORR), as assessed by an IRF and investigator, DOR, as assessed by an IRF and investigator ? To evaluate the quality of life of patients treated with tiragolumab plus atezolizumab compared with durvalumab in the PPAS and FAS ? To evaluate the efficacy of tiragolumab plus atezolizumab compared with durvalumab in the PPAS and FAS on the basis of PFS rate at 12, 18, and 24 months, OS rate at 12, 24, 36, and 48 months, and time to distant metastasis (TTDM) ? To evaluate the safety and tolerability of tiragolumab plus atezolizumab compared with durvalumab.;Primary end point(s): 1. PFS, as assessed by an IRF, defined as the time from randomization to the first occurrence of disease progression, as determined by the IRF according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1), or death from any cause, whichever occurs first (PPAS) 2. PFS, as assessed by an IRF (FAS).;Timepoint(s) of evaluation of this end point: 1. Up to approximately 114 months (approximately 9.5 years) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Overall survival (FAS and PPAS) 2. PFS, as assessed by the investigator (FAS and PPAS) 3. Confirmed ORR, as assessed by an IRF (FAS and PPAS) 4. Confirmed ORR, as assessed by the investigator (FAS and PPAS) 5. DOR, as assessed by an IRF (FAS and PPAS) 6. DOR, as assessed by the investigator (FAS and PPAS) 7. Time to confirmed deterioration (TTCD) (FAS and PPAS) 8. PFS rate at 12, 18, and 24 months (FAS and PPAS) 9. OS rate at 12, 24, 36, and 48 months (FAS and PPAS) 10. TTDM (FAS and PPAS) 11. Incidence and severity of adverse events with severity graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0).;Timepoint(s) of evaluation of this end point: 1-7. Up to approximately 114 months (approximately 9.5 years) 8. At 12 months, 18 months, and 24 months 9. At 12 months, 24 months, 36 months, and 48 months 10-11. Up to approximately 114 months (approximately 9.5 years) | — |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, China, Czechia, France, Germany, Greece, Hong Kong, Hungary, Israel, Italy, Japan, Korea, Republic of, Netherlands, Poland, Portugal, Spain, Taiwan, Thailand, Türkiye, United Kingdom, United States
Contacts
Public ContactTrial Information Support Line-TISL
F. Hoffmann-La Roche Ltd
Outcome results
None listed