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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

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

366

The mean of age was 64 (atezolizumab plus cabozantinib) and 66 (Docetaxel) years. Other baseline characteristics were generally well balanced between arms.

From October 2020 to November 2021, 366 patients at 97 study sites in 15 countries were enrolled, with 186 patients assigned to atezolizumab plus cabozantinib and 180 to docetaxel. Overall, 185 patients in the atezolizumab plus cabozantinib arm and 167 in the docetaxel arm received >=1 dose of study treatment were included in the safety-evaluable population.

Any-cause adverse events (AEs) occurred in 182 (98.4%) of patients in the atezolizumab plus cabozantinib arm and 157 (94.0%) in the docetaxel arm (grade 3/4 AEs in 89 [48.1%] and 76 [45.5%], respectively). In the atezolizumab plus cabozantinib and docetaxel arms, 177 (95.7%) and 135 (80.8%) patients, respectively, had AEs related to any study treatment. In the atezolizumab plus cabozantinib arm, treatment-related AEs that occurred in >=20% of patients were diarrhea (40.5%), decreased appetite (24.9%), and palmar-plantar erythrodysesthesia syndrome (21.6%). In the docetaxel arm, treatment-related AEs that occurred in >=20% of patients were alopecia (22.2%) and asthenia (21.6%). In the atezolizumab plus cabozantinib and docetaxel arms, 71 (38.4%) and 58 (34.7%) patients, respectively, had serious AEs (SAEs). In the atezolizumab plus cabozantinib arm, SAEs that occurred in >=2% of patients were pneumonia (5.4%), pyrexia (2.7%), and vascular device infection (2.2%). In the docetaxel arm, SAEs that occurred in >=2% of patients were pneumonia (6.0%), febrile neutropenia (4.8%), pneumonitis (3.0%), and respiratory failure (2.4%).

Primary outcome measures: Median OS in the ITT population was 10.7 months (95% CI, 8.8 to 12.3) in the atezolizumab plus cabozantinib arm and 10.5 months (95% CI, 8.6 to 13.6) in the docetaxel arm (stratified HR, 0.88 [95% CI: 0.68 to 1.16]; P = 0.3668). Secondary outcome measures: PFS events occurred in 162 patients (87.1%) in the atezolizumab plus cabozantinib arm and 150 (83.3%) in the docetaxel arm. Median PFS was 4.6 months (95% CI: 4.1 to 5.6) with atezolizumab plus cabozantinib and 4.0 months (95% CI: 3.1 to 4.4) with docetaxel (HR, 0.74 [95% CI: 0.59 to 0.92]). ORR was 11.8% (95% CI, 7.6 to 17.4) in the atezolizumab plus cabozantinib arm and 13.3% (95% CI, 8.7 to 19.2) in the docetaxel arm. Median DOR was 5.6 months (95% CI, 3.1 to 10.3) with atezolizumab plus cabozantinib and 4.3 months (95% CI, 3.3 to 5.6) with docetaxel.

The phase III CONTACT-01 study in metastatic NSCLC previously treated with an anti-PD-1/L1 antibody and platinum agent investigated whether TKI could reinvigorate immune response with ICI refractory. This study didn't meet the primary endpoint of OS. Numerical improvements favoring atezolizumab + cabozantinib over docetaxel were observed for the secondary endpoints of PFS and DOR. The safety profile for atezolizumab + cabozantinib was consistent with previously established safety profiles of each agent.

Mar. 29, 2024

https://ascopubs.org/doi/10.1200/JCO.23.02166

No

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https://jrct.mhlw.go.jp/latest-detail/jRCT2051200065

Clinical trials information

Chugai Pharmaceutical Co., Ltd.

1-1 Nihonbashi-Muromachi 2-Chome Chuo-ku Tokyo

clinical-trials@chugai-pharm.co.jp

Clinical trials information

Chugai Pharmaceutical Co., Ltd.

1-1 Nihonbashi-Muromachi 2-Chome, Chuo-ku Tokyo

+81-120-189-706

clinical-trials@chugai-pharm.co.jp

Complete

Nov. 30, 2020

Interventional

randomized controlled trial

open(masking not used)

active control

parallel assignment

treatment purpose

-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.

-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)
-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.

Both

Non small cell lung cancer

Atezolizumab:Atezolizumab will be administered by IV infusion at a fixed dose of 1200 mg on Day 1 of each 21-day cycle.
Cabozantinib:Cabozantinib will be administered orally, once daily at a dose of 40 mg on Days 1-21 of each cycle.
Docetaxel:Docetaxel will be administered by IV infusion at a fixed dose of 1200 mg on Day 1 of each 21-day cycle.

efficacy
overall survival

safety,efficacy,phamacokinetics
progression-free survival etc
Observation/Inspection, RECIST v1.1

+81-78-929-1151

Sept. 14, 2020

Australia/Austria/Belgium/France/Germany/Greece/Italy/Republic of Korea/Poland/Portugal/Russia/Spain/United Kingdom/United States