Single Arm Phase 2 Trial of Atezolizumab and Bevacizumab in Epidermal Growth Factor Receptor (EGFR) Mutant Non-Small Cell Lung Cancer in Patients With Progressive Disease After Receiving Osimertinib (TOP 1901)
Overview
- Phase
- Phase 2
- Intervention
- Atezolizumab
- Conditions
- Non Small Cell Lung Cancer
- Sponsor
- Duke University
- Enrollment
- 7
- Locations
- 1
- Primary Endpoint
- Objective Response Assessed by the Investigator Using RECIST 1.1
- Status
- Terminated
- Last Updated
- 2 years ago
Overview
Brief Summary
The purpose of this study is to investigate the safety and efficacy of giving atezolizumab combined with bevacizumab in patients with stage 4 epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) whose cancer has gotten worse while receiving osimertinib.
Detailed Description
This study will be single arm, open label, phase 2 study which will include patients with stage 4 NSCLC patients with EGFR mutations and who have progressed on osimertinib. Although both atezolizumab and bevacizumab are approved for the treatment of NSCLC, the combination of atezolizumab and bevacizumab has not been approved by the FDA for the treatment of specific non-small cell lung cancer (NSCLC). Patients who have one of the following EGRF mutations: exon 19 or exon 21 L858R with progressive disease on osimertinib may be eligible to participate in this study. If enrolled into the study, the study team will give the patient atezolizumab (1200 mg) combined with bevacizumab (15 mg/kg) every 3 weeks intravenously. As part of this study, the patient will have blood samples, other tests, exams, and procedures done for study purposes and their standard of care. Patient participation in the study will last for up to 2 years after completion of the last dose of the study drug or until your condition worsens or intolerable adverse events as deemed by the study doctor. There are possible patient risks to this study that include but are not limited to diarrhea, itching, rash, and a feeling of weakness.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Age ≥18 years
- •Histologic documentation of primary lung carcinoma, non-squamous histology with EGFR exon deletion 19 or exon 21 L858R mutation
- •Stage IV disease according to the 8th Edition of the American Joint Committee on Cancer staging system
- •Disease progression on osimertinib
- •Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1 (appendix 1)
- •Measureable disease as defined by RECIST 1.1 (appendix 2)
- •The following laboratory values obtained ≤ 30 days prior to starting study therapy
- •ANC ≥ 1, 500 / mm3
- •Platelet count, ≥ 100,000 / mm3
- •Hemoglobin ≥ 9.0 g / dL
Exclusion Criteria
- •Mixed, non-small cell and small cell tumors or mixed adenosquamous carcinomas with a predominant squamous component.
- •Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown: pregnant women, nursing women, men or women of childbearing potential who are unwilling to employ adequate contraception
- •Other active malignancy ≤ 2 years prior to study cycle 1 day 1 of study therapy. EXCEPTIONS: Nonmelanotic skin cancer or carcinoma-in-situ of the cervix, or adequately treated stage I or II cancer. NOTE: If there is a history of prior malignancy, they must not be receiving other specific treatment (i.e. hormonal therapy) for their cancer.
- •History of myocardial infarction or other evidence of arterial thrombotic disease (angina), symptomatic congestive heart failure (New York Heart Association ≥ grade 2), unstable angina pectoris, or ventricular arrhythmia with ≤ 6 months
- •History of cerebral vascular accident (CVA) or transient ischemic attack (TIA) ≤ 6 months prior to study cycle 1 day 1 of study therapy.
- •History of bleeding diathesis or coagulopathy.
- •Inadequately controlled hypertension (systolic blood pressure of \>160 mmHg or diastolic pressure \>100 mmHg on anti-hypertensive medications). Note: History of hypertensive crisis or hypertensive encephalopathy not allowed.
- •Serious non-healing wound, ulcer, bone fracture, or have undergone a major surgical procedure, open biopsy, or significant traumatic injury ≤ 28 days or core biopsy ≤ 7 days prior to starting therapy
- •History of abdominal fistula, gastrointestinal perforation, or intraabdominal abscess ≤6 months prior to study cycle 1 day 1 of study therapy.
- •Known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies.
Arms & Interventions
atezolizumab and bevacizumab
Atezolizumab 1200 mg IV every 3 weeks and bevacizumab 15 mg/kg IV every 3 weeks (1 cycle=3 weeks)
Intervention: Atezolizumab
atezolizumab and bevacizumab
Atezolizumab 1200 mg IV every 3 weeks and bevacizumab 15 mg/kg IV every 3 weeks (1 cycle=3 weeks)
Intervention: Bevacizumab
Outcomes
Primary Outcomes
Objective Response Assessed by the Investigator Using RECIST 1.1
Time Frame: Up to 2 years
Objective response (complete or partial response) rate (ORR) is assessed by the investigator using Response Evaluation Criteria in Solid Tumors RECIST 1.1 (brand name) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Secondary Outcomes
- Progression Free Survival as Measured by RECIST v1.1 RECIST 1.1 (Brand Name) as Assessed by the Investigator.(Up to 2 years)
- Overall Survival as Noted by Follow-up Via Composite of Telephone or Medical Record Review.(Up to 2 years)
- Number of Participants With AEs as Measured by Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03(Up to 2 years)