Non small cell lung cancer MedDRA version: 20.0 Level: PT Classification code 10061873 Term: Non-small cell lung cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Tecentriq
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: ATEZOLIZUMAB
Current Sponsor code: RO5541267
Other
Sponsors
Fundación GECP
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female, aged = 18 years old 2. ECOG performance status of 0 or 1. 3. Histologically or cytologically confirmed, Stage IIIB or IV non-squamous NSCLC according to 8th version of the International Association for the Study of Lung Cancer Staging Manual in Thoracic Oncology 4. No prior treatment for Stage IIIB or IV non-squamous NSCLC. 5. Patients who have received prior neo-adjuvant, adjuvant chemotherapy, radiotherapy, or chemo-radiotherapy with curative intent for non-metastatic disease must have experienced a treatment-free interval of at least 6 months from randomization since the last chemotherapy, radiotherapy, or chemo-radiotherapy. 6. Patients with a treated asymptomatic CNS metastasis are eligible, provided they meet all of the following criteria: a. Only supratentorial and cerebellar metastases allowed (i.e., no metastases to midbrain, pons, medulla or spinal cord). b. No ongoing requirement for corticosteroids as therapy for CNS disease. c. No stereotactic radiation within 7 days or whole-brain radiation within 14 days prior to randomization. d. No evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study. Patients with new asymptomatic CNS metastases detected at the screening scan must receive radiation therapy and/or surgery for CNS metastases. Following treatment, these patients may then be eligible without the need for an additional brain scan prior to inclusion, if all other criteria are met. 7. Patients with high-intermediate Tumour Mutational Burden analysed by Foundation Medicine (=10 mutations/ MB) performed by a Foundation Medicine laboratory on previously obtained archival tumour tissue or tissue obtained from a biopsy at pre-screening (sample must fulfil minimal sample requirements of 20% tumour cellularity and a minimum surface of 25mm2). 8. Measurable disease, as defined by RECIST v1.1. Previously irradiated lesions can only be considered as measurable disease if disease progression has been unequivocally documented at that site since radiation and the previously irradiated lesion is not the only site of disease. 9. Adequate hematologic and organ function defined by the following laboratory results obtained within 14 days prior to randomization • 10. All patients are notified of the investigational nature of this study and signed a written informed consent in accordance with institutional and national guidelines, including the Declaration of Helsinki prior to any trial-related intervention. 11. For female patients of childbearing potential, agreement (by patient and/or partner) to use a highly effective form(s) of contraception that results in a low failure rate (< 1% per year) when used consistently and correctly, and to continue its use for 5 months after the last dose of Atezolizumab and/or 6 months after the last dose of Bevacizumab, whichever is later. Such methods include: combined (oestrogen and progestogen containing) hormonal contraception, progestogen-only hormonal contraception associated with inhibition of ovulation together with another additional barrier method always containing a spermicide, intrauterine device (IUD): intrauterine hormone-releasing
Exclusion criteria
Exclusion criteria: 1. Patients with a sensitizing mutation in the epidermal growth factor receptor (EGFR) gene. 2. Patients with an anaplastic lymphoma kinase (ALK) fusion oncogene. 3. Patients with an STK-1 Ligand alteration. 4. Patients with MDM2 amplification. 5. Patients with ROS1 translocations. 6. Active or untreated CNS metastases as determined by CT or magnetic resonance imaging (MRI) evaluation during screening and prior radiographic assessments. 7. Spinal cord compression not definitively treated with surgery and/or radiation or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for > 2 weeks prior to randomization. 8. Leptomeningeal disease. 9. Uncontrolled tumour-related pain. Patients requiring pain medication must be on a stable regimen at study entry. Symptomatic lesions amenable to palliative radiotherapy (e.g., bone metastases or metastases causing nerve impingement) should be treated prior to initiation of study drug. Patients should be recovered from the effects of radiation. There is no required minimum recovery period. Asymptomatic metastatic lesions whose further growth would likely cause functional deficits or intractable pain (e.g., epidural metastasis that is not currently associated with spinal cord compression) should be considered for locoregional therapy, if appropriate, prior to initiation of study drug. 10. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently). Patients with indwelling catheters (e.g., PleurX®) are allowed. 11. Uncontrolled or symptomatic hypercalcemia (> 1.5 mmol/L ionized calcium or Ca > 12 mg/dL or corrected serum calcium > ULN). 12. Malignancies other than NSCLC within 5 years prior to randomization, with the exception of those with a negligible risk of metastasis or death (e.g., expected 5-year OS > 90%) treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous-cell skin cancer, localized prostate cancer treated surgically with curative intent, ductal carcinoma in situ treated surgically with curative intent).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of Atezolizumab in combination with Bevacizumab as measured by Progression Free Survival (PFS) according to Response Evaluation Criteria in Solid Tumours (RECIST) Version 1.1; Secondary Objective: • To evaluate the ORR of Atezolizumab in combination with Bevacizumab as measured by investigator-assessed overall response rate (ORR) according to RECIST v1.1. • To evaluate the efficacy of Atezolizumab in combination with Bevacizumab as measured by investigator-assessed duration of response (DOR), time to response (TTR) according to RECIST v1.1, ORR, PFS and DOR according to immune-related response criteria; irRC. • To evaluate the PFS and OS rate at 1 and 2 years of Atezolizumab in combination with Bevacizumab and according to PDL1 expression • To evaluate the safety and tolerability of Atezolizumab in combination with Bevacizumab. • To evaluate patient-reported outcomes (PROs) of lung cancer symptoms ;Primary end point(s): Progression free survival;Timepoint(s) of evaluation of this end point: At the time of the first progression to the study treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Overall response rate Duration of response Quality of life Time to response Overall survival ; Timepoint(s) of evaluation of this end point: Overall response rate: at the end of the study treatment Duration of response: at the end of the study treatment Quality of life: at the end of the study Time to response: at the time when the first response is achieved Overall survival: at the end of the study | — |
Countries
Spain
Contacts
Public ContactEva Pereira
Fundación GECP
Outcome results
None listed