Study of Atezolizumab in Combination with Cabozantinib Versus Docetaxel in Patients with Metastatic Non-Small Cell Lung Cancer Previously Treated With an Anti-PD-L1/PD-1 Antibody and Platinum-Containing Chemotherapy
- Conditions
- on-small cell lung cancer (NSCLC)MedDRA version: 21.1Level: PTClassification code 10029522Term: Non-small cell lung cancer stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2020-000100-11-FR
- Lead Sponsor
- F. Hoffman-La Roche Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 350
- Age >= 18 years
- Histologically or cytologically confirmed metastatic NSCLC
- Documented radiographic disease progression during or following treatment with platinum-containing doublet chemotherapy and anti-PD-L1/PD-1 antibody, administered concurrently or sequentially for metastatic NSCLC
- Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 outside the central nervous system (CNS) as assessed by investigator
- Known PD-L1 status or availability of tumor tissue for central PD-L1 testing
- Eastern Cooperative Oncology Group performance status score of 0 or 1
- Recovery to baseline or Grade <= 1 National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 from toxicities related to any prior treatments, unless adverse events are clinically nonsignificant and/or stable on supportive therapy in the opinion of the investigator
- Adequate hematologic and end-organ function
- For women of childbearing potential: agreement to remain abstinent or use contraception, and agreement to refrain from donating eggs, for 5 months after the final dose of atezo and/or 4 months after the final dose of cabo
- For men: agreement to remain abstinent or use contraceptive methods, and agreement to refrain from donating sperm for 4 months after the final dose of cabo, or for 6 months after the final dose of docetaxel
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 175
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 175
- Prior therapy with the following agents for NSCLC: Cabo, Docetaxel, Combination of an anti-PD-L1/PD-1 antibody concurrently with a vascular endothelial growth factor -targeting tyrosine kinase inhibitor
- Treatment with investigational therapy within 28 days prior to initiation of study treatment
- Documentation of known sensitizing mutation in the epidermal growth factor receptor (EGFR) gene or anaplastic lymphoma kinase (ALK) fusion oncogene
- Symptomatic, untreated, or actively progressing CNS metastases
- History of leptomeningeal disease
- Uncontrolled tumor-related pain, pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures, uncontrolled or symptomatic hypercalcemia
- Any other active malignancy at the time of initiation of study treatment or diagnosis of another malignancy within 3 years prior to initiation of study treatment that requires active treatment, except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, incidental prostate cancer, or carcinoma in situ of the prostate, cervix, or breast
- Significant cardiovascular disease within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina
- Stroke, transient ischemic attack, myocardial infarction or other symptomatic ischemic events within 6 months of initiation of study treatment
- Active tuberculosis
- Severe infection within 4 weeks prior to initiation of study treatment
- Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment
- Current treatment with anti-viral therapy for HBV
- Ongoing Grade = 2 sensory or motor neuropathy
- Active or history of autoimmune disease or immune deficiency
- Pharmacologically uncompensated, symptomatic hypothyroidism
- Administration of 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
- Treatment with systemic immunostimulatory agents within 4 weeks or 5 drug-elimination half-lives prior to initiation of study treatment
- Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during study treatment
- Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab formulation
- History of severe hypersensitivity to docetaxel or to other drugs formulated with polysorbate 80
- Concomitant anticoagulation with oral anticoagulants or platelet inhibitors
- Thromboembolic event within 6 months before initiation of study treatment
- History of risk factors for torsades de pointes
- Corrected QT interval corrected through use of Fridericia's formula > 480 ms per ECG within 14 days before initiation of study treatment
- Uncontrolled hypertension defined as systolic blood pressure > 150 mm Hg or diastolic BP > 90 mm Hg despite optimal antihypertensive treatment
- Abdominal fistula, bowel obstruction, GI perforation, or intra-abdominal abscess within 6 months before initiation of study treatment
- Known cavitating pulmonary lesion(s) or known endobronchial disease manifestation
- Lesions invading major pulmonary blood vessels
- Clinically significant hematuria, hematemesis, hemoptysis of > 0.5 teaspoon (2.5
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the efficacy of atezolizumab in combination with cabozantinib compared with docetaxel monotherapy in patients with metastatic NSCLC who were previously treated with an anti- anti-Programmed death-ligand 1 (PD-L1)/PD-1 antibody and platinum-containing chemotherapy;Secondary Objective: To evaluate the safety of atezolizumab and cabozantinib compared with docetaxel monotherapy in this patient population<br>To characterize the pharmacokinetic (PK) profile of atezolizumab and cabozantinib<br>To evaluate the immune response to atezolizumab and cabozantinib <br>;Primary end point(s): Duration of Overall Survival (OS);Timepoint(s) of evaluation of this end point: Up to approximately 43 months
- Secondary Outcome Measures
Name Time Method