A Phase III, Multicenter, Randomized, Open-Label, Controlled Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Atezolizumab Given in Combination With Cabozantinib Versus Docetaxel Monotherapy in Patients With Metastatic Non-Small Lung Cancer Previously Treated With an Anti-PD-L1/PD-1 Antibody and Platinum-Containing Chemotherapy

Hoffmann-La Roche92 sites in 11 countries366 target enrollmentOctober 1, 2020

ConditionsCarcinoma, Non-Small-Cell Lung

InterventionsCabozantinib Atezolizumab Docetaxel

DrugsCabozantinib Atezolizumab Docetaxel

Overview

Phase: Phase 3
Intervention: Cabozantinib
Conditions: Carcinoma, Non-Small-Cell Lung
Sponsor: Hoffmann-La Roche
Enrollment: 366
Locations: 92
Primary Endpoint: Overall Survival (OS)
Status: Completed
Last Updated: 4 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief 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.

Registry

clinicaltrials.gov

Start Date

October 1, 2020

End Date

January 17, 2025

Last Updated

4 months ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Hoffmann-La Roche

Responsible Party

Sponsor

Eligibility Criteria

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

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
•Patients with known ROS1 rearrangements, BRAF V600E mutations, or other actionable oncogenes with approved therapies if available
•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

Arms & Interventions

Atezolizumab + Cabozantinib

Participants received atezolizumab on Day 1 of each 21-day cycle and cabozantinib orally once daily on Days 1-21 of each cycle.

Intervention: Cabozantinib

Atezolizumab + Cabozantinib

Participants received atezolizumab on Day 1 of each 21-day cycle and cabozantinib orally once daily on Days 1-21 of each cycle.

Intervention: Atezolizumab

Docetaxel

Participants received docetaxel on Day 1 of each 21-day cycle.

Intervention: Docetaxel

Outcomes

Primary Outcomes

Overall Survival (OS)

Time Frame: Up to approximately 24 months

OS was defined as the time from randomization to death from any cause. Participants alive at the time of the analysis were censored at the date when they were last known to be alive as documented by the investigator. Kaplan-Meier method was used to estimate the median. 95% CI for median was computed using the method of Brookmeyer and Crowley.

Secondary Outcomes

Progression-Free Survival (PFS) as Determined by Investigator(Up to approximately 24 months)
Confirmed Objective Response Rate (ORR) as Determined by Investigator(Up to approximately 24 months)
Maximum Plasma Concentration (Cmax) of Cabozantinib(Predose on Day 1 of Cycles 1, 2, 3, 4, and 5 (Cycle= 21 days))
Duration of Response (DOR) as Determined by Investigator(Up to approximately 24 months)
Minimum Plasma Concentration (Cmin) of Cabozantinib(Predose on Day 1 of Cycles 1, 2, 3, 4, and 5 (Cycle= 21 days))
Time to Confirmed Deterioration (TTCD) in Patient-reported Physical Functioning (PF)(Up to approximately 24 months)
TTCD in Patient-reported Global Health Status (GHS)(Up to approximately 24 months)
PFS Rates Assessed by Investigator(6 months and 1 year)
OS Rates(1 and 2 years)
Percentage of Participants With Adverse Events (AEs)(Up to approximately 41.4 months)
Maximum Serum Concentration (Cmax) of Atezolizumab(30 minutes (min) postdose on Day 1 of Cycle 1 (Cycle= 21 days))
Minimum Serum Concentration (Cmin) of Atezolizumab(Predose on Day 1 of Cycles 1, 2, 3, 4, 8, 12 and 16 (Cycle= 21 days))
Number of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab(Pre-dose on Day 1 of Cycles 1, 2, 3, 4, 8, 12, 16 and post-treatment follow-up (≤ 30 days after final dose) (Cycle= 21 days))