A Single Arm, Phase II Study of Atezolizumab (MPDL3280A, Anti-PD-L1 Antibody) in Combination With Bevacizumab in Patients With EGFR Mutation Positive Stage IIIB-IV Non-Squamous Non-Small Cell Lung Cancer Pretreated With Epidermal Growth Factor Receptor Tyrosine-Kinase Inhibitors

Hoffmann-La Roche10 sites in 1 country23 target enrollmentSeptember 9, 2020

ConditionsCarcinoma, Non-Small-Cell Lung

InterventionsAtezolizumab Bevacizumab

DrugsAtezolizumab Bevacizumab

Overview

Phase: Phase 2
Intervention: Atezolizumab
Conditions: Carcinoma, Non-Small-Cell Lung
Sponsor: Hoffmann-La Roche
Enrollment: 23
Locations: 10
Primary Endpoint: Objective Response Rate (ORR)
Status: Completed
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is an open-label, single-arm, phase II, multicenter study designed to evaluated the efficacy and safety of atezolizumab in combination with bevacizumab in PD-L1-selected patients with Stage IIIB-IV Non-Squamous NSCLC harbored EGFR mutation after EGFR TKI therapy.

Registry

clinicaltrials.gov

Start Date

September 9, 2020

End Date

February 10, 2023

Last Updated

last year

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Hoffmann-La Roche

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Life expectancy ≥ 10 months
•Histologically or cytologically confirmed stage IIIB, IIIC, or IV non-squamous NSCLC. Patients with tumors of mixed histology are eligible if the major histological component appears to be non-squamous.
•No prior treatment for Stage IIIB, IIIC, or IV non-squamous NSCLC, with the following exceptions:
•Patients with a sensitizing mutation in the EGFR gene must have experienced disease progression or were intolerant to treatment with one or more EGFR TKIs. Patients who have progressed on or were intolerant to first-line osimertinib or other thirdgeneration EGFR TKIs are eligible.
•Patients who have progressed on or were intolerant to first- or second-generation EGFR TKIs, and who have no evidence of the EGFR T790M mutation after TKI therapy are eligible.
•Patients who have progressed on or were intolerant to first- or second-generation EGFR TKIs and who have evidence of the T790M mutation must have also progressed on or were intolerant to osimertinib to be eligible.
•TKIs approved for treatment of NSCLC discontinued \>7 days prior to enrollment.
•Measurable disease per RECIST v1.
•PD-L1 expression of ≥1% as documented through central testing of a representative tumor tissue specimen either from previously obtained archival tumor tissue or tissue obtained from a biopsy at screening
•ECOG Performance Status of 0-1

Exclusion Criteria

•Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases as determined by CT or MRI evaluation during screening and prior radiographic assessments
•History of leptomeningeal disease
•Prior chemotherapy or other systemic therapy for stage IIIB, IIIC, or IV disease
•Active or history of autoimmune disease or immune deficiency
•History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
•Active tuberculosis
•Significant cardiovascular disease within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina
•History of malignancy other than NSCLC within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death
•Prior allogeneic stem cell or solid organ transplantation
•Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the final dose of atezolizumab

Arms & Interventions

Atezolizumab plus Bevacizumab

Participants will receive atezolizumab plus bevacizumab intravenously on Day 1 of each cycle. Treatment will continue until progressive disease, unacceptable toxicity, or death.

Intervention: Atezolizumab

Atezolizumab plus Bevacizumab

Participants will receive atezolizumab plus bevacizumab intravenously on Day 1 of each cycle. Treatment will continue until progressive disease, unacceptable toxicity, or death.

Intervention: Bevacizumab

Outcomes

Primary Outcomes

Objective Response Rate (ORR)

Time Frame: Baseline up to approximately 10 months

Objective response rate (ORR) was defined as the percentage of participants with a complete response (CR) or partial response (PR) on two consecutive occasions \>=4 weeks apart, as determined by the investigator according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1).

Secondary Outcomes

Duration of Objective Response (DOR)(Baseline up to approximately 2.5 years)
Time to Response (TTR)(Baseline up to approximately 2.5 years)
Disease Control Rate (DCR)(Baseline up to approximately 2.5 years)
PFS Rate at 6 and 12 Months(Baseline to 6 months and 12 months)
Duration of Objective Response (DOR) According to iRECIST(Baseline up to approximately 2.5 years)
Progression-Free Survival (PFS) Rate at 12 Months According to iRECIST(Baseline up to approximately 12 months)
Change From Baseline in Health-Related Quality of Life (HRQoL) and Health Status(Baseline up to approximately 1 year)
Overall Survival (OS)(Baseline until death due to any cause (up to approximately 2.5 years))
Progression-Free Survival (PFS)(Baseline up to approximately 2.5 years)
OS Rate at 1 and 2 Years(Baseline to 1 and 2 Years)
Percentage of Participants With Adverse Events(Baseline up to approximately 2.5 years)
Percentage of Participants With Serious and Non-Serious Immune-Mediated Adverse Events (irAEs)(Baseline up to approximately 2.5 years)
Objective Response Rate (ORR) According to iRECIST(Baseline up to approximately 2.5 years)
Disease Control Rate (DCR) According to iRECIST(Baseline up to 2 years and approximately 5 months)
Progression-Free Survival (PFS) According to iRECIST(Baseline up to approximately 2.5 years)
Time to Deterioation (TTD) Using EORTC(Baselsine up to approximately 1 year)
Change From Baseline in Lung Cancer Related Symptoms(Baseline up to approximately 1 year)