Atezolizumab and Bevacizumab in EGFR Mutant NSCLC in Patients With Progressive Disease After Receiving Osimertinib

NCT04099836 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: Pro00103723
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

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.

Conditions

Non Small Cell Lung Cancer

Keywords

EGFR Mutation; Atezolizumab; Bevacizumab; exon L858R; exon 21 L858R

Outcome Measures

Primary Outcomes (1)

• Objective Response Assessed by the Investigator Using RECIST 1.1

  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.

  Up to 2 years

Secondary Outcomes (3)

• 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

Study Arms (1)

atezolizumab and bevacizumab

EXPERIMENTAL

Atezolizumab 1200 mg IV every 3 weeks and bevacizumab 15 mg/kg IV every 3 weeks (1 cycle=3 weeks)

Drug: Atezolizumab; Drug: Bevacizumab

Interventions

Atezolizumab DRUG

1200 mg IV every 3 weeks

Also known as: TECENTRI

atezolizumab and bevacizumab

Bevacizumab DRUG

15 mg/kg IV every 3 weeks

Also known as: Avastin

atezolizumab and bevacizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN)
• Serum Glutamic Oxaloacetic Transaminase (SGOT) (Aspartate Aminotransferase, AST) and Serum Glutamic Pyruvic Transaminase (SGPT) (Alanine Aminotransferase, ALT) ≤2.5 x ULN in patients without liver or bone metastases; \< 5 x ULN in patients with liver or bone metastases.
• Cockcroft-Gault calculated creatinine clearance of ≥ 45 ml/min (appendix 3) or creatinine ≤1.5 x ULN
• Urine protein/creatinine (UPC) ratio ≤1.
• Negative pregnancy test done ≤7 days (or per institutional policy) prior to start of study therapy, for women of childbearing potential only. Female subjects should be using highly effective contraceptive measures, and must have a negative pregnancy test of must have evidence of non-child bearing potential by fulfilling one of the following criteria at screening:

You may not qualify if:

• 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.
• History of hemoptysis ≥ grade 2 (defined as bright red blood of at least 2.5 mL) ≤ 3 months prior to cycle 1 day 1 of study therapy.
• Symptomatic untreated brain metastases which is defined as persistent neurological symptoms or requiring ongoing use of steroids. Asymptomatic untreated brain metastases are allowed if ≤ 1 cm
• Significant vascular disease (e.g. aortic aneurysm surgical repair or recent peripheral arterial thrombosis) ≤6 months prior to starting study therapy
• Radiotherapy to any site for any reason ≤ 14 days prior to study cycle 1 day 1 of study therapy.
• Pre-existing and clinically active interstitial lung disease

Sponsors & Collaborators

• Duke University: lead

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

atezolizumab; Bevacizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Dr. Thomas Stinchcombe
• Organization: Duke University Medical Center

Thomas.stinchcombe@duke.edu

919-681-9509

Study Officials

• Thomas Stinchcombe, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 20, 2019
• First Posted: September 23, 2019
• Study Start: July 9, 2020
• Primary Completion: November 13, 2022
• Study Completion: June 15, 2023
• Last Updated: December 26, 2023
• Results First Posted: December 26, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)