ETOP 15-19 ABC-lung is an international, multi-centre open-label, randomized phase II trial with two non-comparative parallel arms of atezolizumab plus bevacizumab with carboplatin-paclitaxel (Arm A) or atezolizumab, bevacizumab and pemetrexed (Arm B) in patients with stage IIIB-IV non-squamous non-small cell lung cancer (NSCLC) harbouring EGFR mutations after failure of standard EGFR tyrosine kinase inhibitors (TKIs).
Name: Atezolizumab
Name: Bevacizumab
Name: Carboplatin
Name: Paclitaxel
Name: Pemetrexed
Description: The primary objective of this study is to explore the clinical efficacy of atezolizumab and bevacizumab combined with chemotherapy in patients with EGFR-mutant advanced NSCLC after failure of standard EGFR TKIs.
Measure: Progression-free survival (PFS) rate at 12 months according to RECIST v1.1 Time: 12 months from randomisationDescription: To assess the safety and tolerability of the treatment.
Measure: Adverse events according to CTCAE v5.0 Time: from the date of randomisation until 90 days after the last dose of protocol treatmentDescription: OS is defined as the time from the date of randomisation until death from any cause. Censoring will occur at the last follow-up date.
Measure: Overall survival Time: through study completion, from the date of randomisation until death, including OS rate at 12 months.Description: Objective response is defined as best overall response (CR or PR) across all assessment time-points according to RECIST criteria v1.1, from randomisation until the end of protocol treatment.
Measure: Objective response Time: From date of randomisation until date of treatment completion (until documented disease progression, death or any other causes), assessed up to 2 years.Description: Quality of life will be assessed by the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30). The key QoL outcome is the time to deterioration (TTD) in the QLQ-C30 global health status/global QoL.
Measure: Quality of Life Core Questionnaire (EORTC QLQ-C30) Time: from baseline up to 12 months or until disease progression, whatever is first.Description: Lung cancer associated symptoms will be measured by the lung cancer-specific module (QLQ-LC13).
Measure: Quality of Life lung cancer-specific module (QLQ-LC13) Time: from baseline up to 12 months or until disease progression, whatever is first.Description: Extra-cranial progression-free-survival is the time from randomisation to documentation of disease progression outside the central nervous system (CNS) as per RECIST criteria or death, whichever occurred first.
Measure: Extra-cranial PFS Time: through study completion, from date of randomisation to documentation of PD outside the CNS, assessed up to 2 yearsDescription: Intracranial progression-free-survival is defined as the time from randomisation to first documented radiographic evidence of CNS progression. CNS progression is defined as progression due to newly developed CNS lesions and/or progression of pre-existing baseline CNS lesions.
Measure: Intracranial PFS Time: through study completion, from date of randomisation to first documented radiographic evidence of CNS progression, assessed up to 2 years.Allocation: Randomized
Parallel Assignment
There are 3 SNPs
3. Known EGFR mutations genotypes by tissue or ctDNA, patients with common mutations (L858R or Del19) and other rare mutations (e.g. --- L858R ---
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) 6. Treatment with an EGFR TKI therapy for at least 10 days 7. Adequate haematological function: - Haemoglobin greater or equal 90 g/L - Absolute neutrophils count (ANC) greater or equal 1.5× 109/L - Platelet count greater or equal 100× 109/L 8. Adequate renal function: - Creatinine less or equal 1.5× ULN OR - Creatinine clearance greater or equal 45 mL/min (using the Cockcroft-Gault formula) 9. Adequate liver function: - ALT and AST less or equal 2.5× ULN. --- T790M --- --- T790M --- --- L858R ---
S768I, G719X) are eligible. --- S768I ---
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) 6. Treatment with an EGFR TKI therapy for at least 10 days 7. Adequate haematological function: - Haemoglobin greater or equal 90 g/L - Absolute neutrophils count (ANC) greater or equal 1.5× 109/L - Platelet count greater or equal 100× 109/L 8. Adequate renal function: - Creatinine less or equal 1.5× ULN OR - Creatinine clearance greater or equal 45 mL/min (using the Cockcroft-Gault formula) 9. Adequate liver function: - ALT and AST less or equal 2.5× ULN. --- T790M --- --- T790M --- --- L858R --- --- S768I ---
- T790M genotype is allowed If most recent line of treatment (1st or 2nd line) was a first- or second-generation EGFR TKI (e.g. --- T790M ---
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) 6. Treatment with an EGFR TKI therapy for at least 10 days 7. Adequate haematological function: - Haemoglobin greater or equal 90 g/L - Absolute neutrophils count (ANC) greater or equal 1.5× 109/L - Platelet count greater or equal 100× 109/L 8. Adequate renal function: - Creatinine less or equal 1.5× ULN OR - Creatinine clearance greater or equal 45 mL/min (using the Cockcroft-Gault formula) 9. Adequate liver function: - ALT and AST less or equal 2.5× ULN. --- T790M ---
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) 6. Treatment with an EGFR TKI therapy for at least 10 days 7. Adequate haematological function: - Haemoglobin greater or equal 90 g/L - Absolute neutrophils count (ANC) greater or equal 1.5× 109/L - Platelet count greater or equal 100× 109/L 8. Adequate renal function: - Creatinine less or equal 1.5× ULN OR - Creatinine clearance greater or equal 45 mL/min (using the Cockcroft-Gault formula) 9. Adequate liver function: - ALT and AST less or equal 2.5× ULN. --- T790M --- --- T790M ---
6. Squamous cell histologic subtype 7. 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 (e.g. a third-generation EGFR TKI such as osimertinib). --- T790M ---
6. Squamous cell histologic subtype 7. 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 (e.g. a third-generation EGFR TKI such as osimertinib). --- T790M --- --- T790M ---