Chemotherapy naïve, EGFR mutant non-squamous NSCLC, stage IIIB/C (not amenable to radical therapy) or IV. MedDRA version: 21.1 Level: PT Classification code 10029522 Term: Non-small cell lung cancer stage IV System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: PT Classification code 10029521 Term: Non-small cell lung cancer stage IIIB System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts
Conditions
Sponsors
ETOP IBCSG Partners Foundation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Chemotherapy naïve, non-squamous NSCLC, stage IIIB/C (not amenable to radical therapy) or IV. Patients who have received previous adjuvant or neoadjuvant chemotherapy are eligible if the date of last dose of treatment was at least 12 months before randomisation - Known EGFR mutations genotypes by tissue or ctDNA; patients with common mutations (L858R or Del19) and other rare mutations (e.g. S768I, G719X) are eligible - Measurable or evaluable disease by RECIST v1.1 - Disease progression (during or after) or unacceptable side effects from prior treatment with at least one EGFR TKI (TKI washout period = 7 days). If most recent line of treatment (1st or 2nd line) was a third-generation EGFR TKI (e.g. osimertinib): – Patient must be known to be EGFR mutation positive, either on fresh tumour biopsy taken >7 days prior to protocol treatment start or by recent ctDNA analysis (informative ctDNA test, local test). – T790M genotype is allowed. If most recent line of treatment (1st or 2nd line) was a first- or second-generation EGFR TKI (e.g. afatinib, dacomitinib, erlotinib, gefitinib): – Patient must be known to be tissue EGFR T790M wild type (local test) on most recent line of EGFR TKI or if no tissue re-biopsy, no evidence of T790M on ctDNA but identified L858R, del19, S768I or G719X genotypes (informative ctDNA test, local test). - Treatment with an EGFR TKI therapy for at least 30 days - Adequate haematological, renal and liver function (CrCl at least 45ml/min) - Willing to make available surplus tissue obtained at the time of acquired resistance to EGFR TKI 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 50 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 45
Exclusion criteria
Exclusion criteria: - Prior systemic cytotoxic chemotherapy for advanced stage NSCLC - Prior therapy with bevacizumab or other anti-angiogenic agent - Prior immune checkpoint inhibitor therapy - More than two lines of EGFR TKI therapy - Known small-cell lung carcinoma (SCLC) or high grade neuroendocrine carcinoma (if progression biopsy has been performed locally) - Squamous cell histologic subtype - Known EGFR T790M positive genotype by tissue on most recent EGFR TKI progression or ctDNA and have not received an approved EGFR TKI targeting T790M - Active or untreated CNS metastases as determined by brain MRI - Patients with CNS metastases must be non-progressive by RECIST v1.1 and symptomatically stable with no ongoing requirement for corticosteroids as therapy for CNS disease; anticonvulsants at a stable dose allowed. - Radiotherapy in target lesions within 4 weeks of randomization - QTc of grade =3 according to CTCAE v5.0 - Active autoimmune disease that has required systemic treatment in past 2 years - Active or uncontrolled HIV, tuberculosis, hepatitis B or C infection - Inadequately controlled hypertension (defined as systolic blood pressure >150 mmHg and/or diastolic blood pressure >100 mmHg). Anti-hypertensive therapy to achieve these parameters is allowable. - Prior history of hypertensive crisis or hypertensive encephalopathy - Significant vascular disease (e.g. aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to randomization - History of haemoptysis (>=2.5 ml of bright red blood per episode) within 1 month prior to randomization - Recent surgery: Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to the first dose of bevacizumab: - Major surgery of significant traumatic injury within 28 days prior to the first dose of bevacizumab - Minor surgical procedures within 7 days, or placement of vascular access device 2 days prior to the first dose of bevacizumab - Serious, non-healing wound, active ulcer, or untreated bone fracture - Proteinuria, as demonstrated by urine dipstick or >1.0 g of protein in a 24-hour urine collection - Any unresolved toxicities from prior therapy greater than CTCAE v5.0 grade 1 at the time of starting trial treatment with the exception of Alopecia - History of active diverticulitis
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to explore the clinical efficacy of atezolizumab and bevacizumab combined with chemotherapy in EGFR mutated patients after failure of standard EGFR targeted therapies.;Secondary Objective: To further assess the efficacy and safety of atezolizumab and bevacizumab combined with chemotherapy. To evaluate symptom-specific and global quality of life. To explore the relationship between baseline biomarkers and measures of efficacy to protocol treatment. To assess exploratory biomarkers in archival and/or fresh tumour tissue, blood samples, oropharyngeal swabs and faecal samples and their association with disease status and/or response to study treatment. ;Primary end point(s): Progression-free survival (PFS) rate at 12 months according to RECIST v1.1. ;Timepoint(s) of evaluation of this end point: - 12 months from date of randomisation | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Objective response rate according to RECIST v1.1 - Extra-cranial PFS - Intracranial PFS - Overall survival, including OS rate at 12 months - Adverse events according to CTCAE v5.0 - Patient reported quality of life - prior use of 3rd generation TKI, EGFR mutation subtype and PD-L1 expression - Sequencing of specific gene panels - Tumour mutation burden - Microbiome analysis;Timepoint(s) of evaluation of this end point: - Objective response: across all assessment time-points from rando until the end of protocol treatment - Extra-cranial PFS: from rando to disease progression - Intracranial PFS: from rando to first documented radiographic evidence of CNS progression - Overall survival: time from the date of rando until death from any cause. Censoring will occur at the last follow-up date. - Adverse events: from date of signature of the IC until 90 days after last dose of protocol treatment - QoL: from baseline up to 12 months after rando - Prior use of 3rd generation TKI, EGFR mutation subtype and PD-L1 expression: at screening - Sequencing of specific gene panels: baseline, D1C2, D1C4, progression - Tumor mutation burden: baseline - Microbiome analysis: baseline, D1C2, D1C4, progression | — |
Countries
Germany, Korea, Republic of, Singapore, Spain, Switzerland, United Kingdom
Contacts
Public ContactCoordinating Center
ETOP IBCSG Partners Foundation
Outcome results
None listed