lung cancer Non-small cell lung cancer
Conditions
Interventions
In the experimental arm, atezolizumab will be administered to patients by IV
infusion at a fixed dose of 1680 mg, followed by tiragolumab at a fixed dose of
840 mg administered by IV infusion on Day
Sponsors
Roche Nederland B.V.
Eligibility
Age
18 Years to 99 Years
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 non-squamous histology - Whole-body PET-CT scan for the purposes of staging, performed prior and within 42 days of the first dose of concurrent chemoradiotherapy (CRT) - At least two prior cycles of platinum-based chemotherapy concurrent with radio therapy (cCRT), 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 CRT must have been at a total dose of radiation of 60 Gy±10% (54 Gy to 66 Gy) administered by intensity-modulated radiotherapy (preferred) or 3D-conforming technique - No progression during or following concurrent platinum-based CRT - Tumor PD-L1 expression, 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.
Exclusion criteria
Exclusion criteria: - Any history of prior NSCLC - NSCLC known to have a mutation in the epidermal growth factor mutation and/or an anaplastic lymphoma kinase translocation - 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 concurrent CRT 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 - 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-[antiTNF-alpha]agents) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressivemedication during study treatment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| - To evaluate the efficacy of tiragolumab plus atezolizumab compared with durvalumab with durvalumab in the programmed death ligand 1 positive analysis set (PPAS) on the basis of PFS, as assessed by an IRF as assessed by an independent review facility (IRF) - 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. | — |
Secondary
| Measure | Time frame |
|---|---|
| The secondary efficacy objective for this study is to evaluate the efficacy of atezolizumab plus tiragolumab compared with durvalumab in the ITT and the PD-L1-positive populations on the basis of the following endpoints: - To evaluate the efficacy of tiragolumab plus atezolizumab compared with durvalumab in the FAS and PPAS 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 FAS and PPAS - To evaluate the efficacy of tiragolumab plus atezolizumab compared with durvalumab on the basis of PFS rate at 12, 18, and 24 months (FAS and PPAS), OS rate at 12, 24, 36, and 48 months (FAS and PPAS), and time to distant metastasis (TTDM) (FAS and PPAS) - To evaluate the safety and tolerability of tiragolumab plus atezolizumab compared with durvalumab. See chapter 2 of protocol for all endpoints | — |
Countries
Netherlands
Outcome results
None listed