Clinical Trials Logo

Clinical Trial Summary

NSCLC patients with low expression level of PD-L1, esp. those with its level less than 1%, do not derive much benefit from anti-PD-1/L1 therapy (e.g. atezoilzumab). In this study, investigators hypothesize that the combination of cabozantinib (a multi-kinase inhibitor) and atezolizumab will result in better therapeutic value.


Clinical Trial Description

For metastatic/advanced non-small cell (NSCLC) patients who do not have targetable mutations, the combination of chemotherapy with immunotherapy targeting the programmed death-1 and its ligand (PD-1/L1) is now a standard of care. In addition, recent studies also demonstrated that immunotherapy doublet using anti-PD-1 agent nivolumab and anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) agent ipilimumab could be another valid option. However, largely due to the immunosuppressive tumor microenvironment, the therapeutic response remains suboptimal in NSCLC patients with PD-L1 tumor proportion score (TPS) lower than 1% (aka PD-L1 negative). For example, the objective response rate (ORR) in KEYNOTE-189 was 32.3% using pembrolizumab plus chemotherapy, and only 27.3% in Checkmate 227 study using nivolumab and ipilimumab, in the PD-L1 negative population. These observations necessitate the search for novel combinations to benefit our PD-L1 negative NSCLC patients. The investigators hypothesize that the combination of cabozantinib and atezolizumab is such an innovative strategy based on the following rationales: 1) cabozantinib is a multi-kinase inhibitor, and some of the targets, for example the vascular endothelial growth factor (VEGF) pathway is notorious to confer immune suppressive tumor microenvironment. In fact, our previous study has demonstrated that anti-VEGF synergizes anti-PD-1 in preclinical model. Consistent with this, cabozantinib has been shown to increase tumor infiltrative cytotoxic CD8+ T cells, reduce immune suppressive T regulatory cells (Tregs) and myeloid-derived suppressor cells (MDSCs), as well as activate anti-tumor innate immunity in multiple solid tumors; 2) at the animal level, cabozantinib was found synergistic with anti-PD-1 agents to elicit anti-tumor immune response; and 3) more importantly, at the human level, the combination of cabozantinib with atezolizumab was found safe in Cohort 7 of the phase 1b COSMIC-021 study and achieved 27% ORR in previously immunotherapy-treated NSCLC - suggesting a potentially higher efficacy if such combination is to be used in the 1st line setting. The investigators therefore propose here the combination of cabozantinib and atezolizumab to be used as the 1st line treatment for advanced/metastatic NSCLC with negative PD-L1 expression. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT05859217
Study type Interventional
Source University of Kansas Medical Center
Contact Jonathon Barnette
Phone 913-588-5565
Email jbarnette@kumc.edu
Status Not yet recruiting
Phase Phase 2
Start date December 2024
Completion date June 2028

See also
  Status Clinical Trial Phase
Completed NCT03918538 - A Series of Study in Testing Efficacy of Pulmonary Rehabilitation Interventions in Lung Cancer Survivors N/A
Recruiting NCT05078918 - Comprehensive Care Program for Their Return to Normal Life Among Lung Cancer Survivors N/A
Active, not recruiting NCT04548830 - Safety of Lung Cryobiopsy in People With Cancer Phase 2
Completed NCT04633850 - Implementation of Adjuvants in Intercostal Nerve Blockades for Thoracoscopic Surgery in Pulmonary Cancer Patients
Recruiting NCT06037954 - A Study of Mental Health Care in People With Cancer N/A
Recruiting NCT06006390 - CEA Targeting Chimeric Antigen Receptor T Lymphocytes (CAR-T) in the Treatment of CEA Positive Advanced Solid Tumors Phase 1/Phase 2
Recruiting NCT05583916 - Same Day Discharge for Video-Assisted Thoracoscopic Surgery (VATS) Lung Surgery N/A
Completed NCT00341939 - Retrospective Analysis of a Drug-Metabolizing Genotype in Cancer Patients and Correlation With Pharmacokinetic and Pharmacodynamics Data
Not yet recruiting NCT06376253 - A Phase I Study of [177Lu]Lu-EVS459 in Patients With Ovarian and Lung Cancers Phase 1
Recruiting NCT05898594 - Lung Cancer Screening in High-risk Black Women N/A
Active, not recruiting NCT05060432 - Study of EOS-448 With Standard of Care and/or Investigational Therapies in Participants With Advanced Solid Tumors Phase 1/Phase 2
Active, not recruiting NCT03575793 - A Phase I/II Study of Nivolumab, Ipilimumab and Plinabulin in Patients With Recurrent Small Cell Lung Cancer Phase 1/Phase 2
Active, not recruiting NCT03667716 - COM701 (an Inhibitor of PVRIG) in Subjects With Advanced Solid Tumors. Phase 1
Terminated NCT01624090 - Mithramycin for Lung, Esophagus, and Other Chest Cancers Phase 2
Terminated NCT03275688 - NanoSpectrometer Biomarker Discovery and Confirmation Study
Not yet recruiting NCT04931420 - Study Comparing Standard of Care Chemotherapy With/ Without Sequential Cytoreductive Surgery for Patients With Metastatic Foregut Cancer and Undetectable Circulating Tumor-Deoxyribose Nucleic Acid Levels Phase 2
Recruiting NCT06010862 - Clinical Study of CEA-targeted CAR-T Therapy for CEA-positive Advanced/Metastatic Malignant Solid Tumors Phase 1
Recruiting NCT06052449 - Assessing Social Determinants of Health to Increase Cancer Screening N/A
Not yet recruiting NCT06017271 - Predictive Value of Epicardial Adipose Tissue for Pulmonary Embolism and Death in Patients With Lung Cancer
Recruiting NCT05787522 - Efficacy and Safety of AI-assisted Radiotherapy Contouring Software for Thoracic Organs at Risk