A Phase II Open Label Study of Atezolizumab in Combination With Bevacizumab as First Line Treatment for Locally Advanced or Metastasic High-intermediate Tumor Mutation Burden Selected Non-squamous Non-small Cell Lung Cancer Patients.
Overview
- Phase
- Phase 2
- Intervention
- Atezolizumab-Bevacizumab
- Conditions
- Non Small Cell Lung Cancer
- Sponsor
- Fundación GECP
- Enrollment
- 41
- Locations
- 25
- Primary Endpoint
- Efficacy of Atezolizumab in Combination With Bevacizumab - PFS
- Status
- Completed
- Last Updated
- 4 months ago
Overview
Brief Summary
This is a multi-center phase II clinical trial of atezolizumab in combination with bevacizumab as first line treatment for locally advanced or metastasic high-intermediate tumour mutation burden selected NSCLC patients. 102 patients will be enrolled in this trial to examine the efficacy of this combination measured by progression free survival according to response evaluation Criteria in solid tumours (RECIST) version 1.1.
Detailed Description
Chemotherapy-naïve patients high-intermediate TMB (TMB≥10 mutations/MB) and with locally advanced or metastatic non-squamous non-small cell lung cancer patients will be selected. Enroled patientswill receive 1200 mg of atezolizumab and 15mg/Kg of Avastin® (bevacizumab) administered by IV infusion every 21 days (+/- 3 days). The treatment will start within 1-5 days from enrolment. Atezolizumab may continue beyond disease progression per RECIST v1.1 until loss of clinical benefit, unacceptable toxicity, patient or physician decision to discontinue , or death. Bevacizumab will be administered until progression disease, unacceptable toxicity, patient or physician decision to discontinue or death. For all patients, tumour response data collection will continue until disease progression, even if the patient stops study treatment prior to disease progression. The primary endpoint is to evaluate the efficacy of Atezolizumab in combination with Bevacizumab as measured by Progression Free Survival according to RECIST Version 1.1. PFS after enrolment is defined as the time from enrolment to the first occurrence of disease progression or death from any cause, whichever occurs first. Patient accrual is expected to be completed within 1.5 years excluding a run-in-period of 46 months. Treatment and follow-up are expected to extend the study duration to a total of 4.5 years. Patients will be followed 1.5 years after the end of treatment independently of the cause of end of treatment. The study will end once survival follow-up has concluded.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male or female, aged ≥ 18 years old
- •ECOG performance status of 0 or
- •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
- •No prior treatment for Stage IIIB or IV non-squamous NSCLC.
- •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.
- •Patients with a treated asymptomatic CNS metastasis are eligible, provided they meet all of the following criteria:
- •Only supratentorial and cerebellar metastases allowed (i.e., no metastases to midbrain, pons, medulla or spinal cord).
- •No ongoing requirement for corticosteroids as therapy for CNS disease.
- •No stereotactic radiation within 7 days or whole-brain radiation within 14 days prior to randomization.
- •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.
Exclusion Criteria
- •Patients with a sensitizing mutation in the epidermal growth factor receptor (EGFR) gene.
- •Patients with an anaplastic lymphoma kinase (ALK) fusion oncogene.
- •Patients with an STK-1 Ligand alteration.
- •Patients with MDM2 amplification.
- •Patients with ROS1 translocations.
- •Active or untreated CNS metastases as determined by CT or magnetic resonance imaging (MRI) evaluation during screening and prior radiographic assessments.
- •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.
- •Leptomeningeal disease.
- •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.
- •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.
Arms & Interventions
Experimental: Atezolizumab plus Bevacizumab arm
1 group, Atezolizumab 1200mb + Bevacizumab 15 mg/kg (IV),every 21 days.
Intervention: Atezolizumab-Bevacizumab
Outcomes
Primary Outcomes
Efficacy of Atezolizumab in Combination With Bevacizumab - PFS
Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months
To evaluate the efficacy of Atezolizumab in combination with Bevacizumab as measured by Progression Free Survival according to Response Evaluation Criteria in Solid Tumours (RECIST).