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

  • STATUS
    Recruiting
  • participants needed
    350
  • sponsor
    Hoffmann-La Roche
Updated on 19 February 2024
cancer
measurable disease
atezolizumab
docetaxel
lung cancer
cabozantinib
antibody test
carcinoma
hepatitis b surface antigen
hepatitis
stage iv non-small cell lung cancer
hepatitis b
hiv test
programmed cell death 1 ligand 1
dna test
hepatitis b core antibody
non-small cell lung cancer
EGFR
small cell lung cancer
alk gene translocation

Summary

This is a Phase III, multicenter, randomized, open-label study designed to evaluate the efficacy, safety, and pharmacokinetics of atezolizumab given in combination with cabozantinib compared with docetaxel monotherapy in patients with metastatic NSCLC, with no sensitizing EGFR mutation or ALK translocation, who have progressed following treatment with platinum-containing chemotherapy and anti-PD-L1/PD-1 antibody, administered concurrently or sequentially.

Details
Condition Non-Small Cell Lung Cancer, Non-Small Cell Lung Cancer
Age 18years - 100years
Treatment Atezolizumab, Docetaxel, Cabozantinib
Clinical Study IdentifierNCT04471428
SponsorHoffmann-La Roche
Last Modified on19 February 2024

Eligibility

Yes No Not Sure

Inclusion Criteria

Histologically or cytologically confirmed metastatic NSCLC
Documented radiographic disease progression during or following treatment with platinum-containing chemotherapy and anti-PD-L1/PD-1 antibody, administered concurrently or sequentially for metastatic NSCLC
Measurable disease per RECIST v1.1 outside CNS as assessed by investigator
Known PD-L1 status or availability of tumor tissue for central PD-L1 testing
ECOG Performance Status score of 0 or 1
Recovery to baseline or Grade <=1 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
Negative HIV test at screening
Negative hepatitis B surface antigen (HBsAg) test at screening
Negative total hepatitis B core antibody (HBcAb) test at screening, or positive total HBcAb test followed by a negative hepatitis B virus (HBV) DNA test at screening
Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening
For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception, and agreement to refrain from donating eggs
For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agreement to refrain from donating sperm

Exclusion Criteria

Prior therapy with the following agents for NSCLC: Cabozantinib, Docetaxel, Combination of an anti-PD-L1/PD-1 antibody concurrently with a vascular endothelial growth factor (VEGF)R targeting tyrosine kinase inhibitor (TKI)
Treatment with investigational therapy within 28 days prior to initiation of study treatment
Documentation of known sensitizing mutation in the EGFR gene or ALK fusion oncogene
Symptomatic, untreated, or actively progressing CNS metastases
History of leptomeningeal disease
Uncontrolled tumor-related pain
Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (more frequently than once monthly)
Severe hepatic impairment
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, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia
Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment
Current treatment with anti-viral therapy for HBV
Major surgical procedure, other than for diagnosis within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the study
Pregnant or lactating females, or intention of becoming pregnant during the treatment with atezolizumab in combination with cabozantinib in the experimental arm or during the treatment with docetaxel in the control arm, or within 5 months after the final dose of atezolizumab and/or 4 months after the final dose of cabozantinib, whichever is later
Ongoing Grade >= 2 sensory or motor neuropathy
Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjgren syndrome, Guillain-Barr syndrome, or multiple sclerosis with the following exceptions: Patients with a history of autoimmune-mediated hypothyroidism who are on thyroid replacement hormone are eligible for the study. Patients with controlled Type 1 diabetes mellitus are eligible for the study. Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only are eligible for the study provided all of following conditions are met: Rash must cover < 10% of body surface area
Pharmacologically uncompensated, symptomatic hypothyroidism
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
Prior allogeneic stem cell of solid organ transplantation
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 (including, but not limited to, interferon and interleukin 2) within 4 weeks or 5 drug-elimination half-lives (whichever is longer) 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, with the following exceptions: Patients who received acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication are eligible for the study after Medical Monitor confirmation has been obtained. Patients who received mineralocorticoids, corticosteroids for COPD or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for the study
History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins
Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab formulation
Known allergy or hypersensitivity to any component of the cabozantinib formulation
History of severe hypersensitivity to docetaxel or to other drugs formulated with polysorbate 80
Concomitant anticoagulation with oral anticoagulants or platelet inhibitors
History of risk factors for torsades de pointes
Corrected QT interval corrected through use of Fridericia's formula (QTcF) > 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
Tumors invading the GI-tract, active peptic ulcer disease, acute pancreatitis, acute obstruction of the pancreatic or biliary duct, appendicitis, cholangitis, cholecystitis, diverticulitis, gastric outlet obstruction, or inflammatory bowel disease
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 mL) of red blood, coagulopathy, or other history of significant bleeding within 3 months before initiation of study treatment
Serious non-healing wound/ulcer/bone fracture
Malabsorption syndrome
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption are also excluded
Requirement for hemodialysis or peritoneal dialysis
Inability to swallow tablets
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