A Study of Combining Cabozantinib and Atezolizumab for Advanced/Metastatic NSCLC (Cabatezo-1)
- Conditions
- Lung CancerMetastatic NSCLC - Non-Small Cell Lung CancerAdvanced NSCLCNSCLC Stage IV
- Interventions
- Registration Number
- NCT05859217
- Lead Sponsor
- Jun Zhang, MD, PhD
- Brief 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.
- Detailed 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.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 40
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Cabozantinib and Atezolizumab Cabozantinib Cabozantinib 40mg po daily + Atezolizumab 1200mg iv on day 1; 1 cycle = 21 days Cabozantinib and Atezolizumab Atezolizumab Cabozantinib 40mg po daily + Atezolizumab 1200mg iv on day 1; 1 cycle = 21 days
- Primary Outcome Measures
Name Time Method Objective response rate (ORR) through study completion, an average of 1 year From baseline to End of Treatment (EOT) due to disease progression using RECIST criteria 1.1
- Secondary Outcome Measures
Name Time Method Overall survival (OS) From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months Medical Record will be followed to watch survival status
Drug Safety From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months Safety of drugs will be determined by documenting adverse events and the severity of adverse events will be documented using CTCAE Version 5.0
Duration of response (DOR) From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months The response to the study drugs will be determined using RECIST criteria 1.1
Progression-free survival (PFS) From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months The lack of progression will be dertermined using RECIST criteria 1.1
Trial Locations
- Locations (4)
The University of Kansas Cancer Center - Westwood
🇺🇸Kansas City, Kansas, United States
The University of Kansas Cancer Center - Indian Creek
🇺🇸Overland Park, Kansas, United States
The University of Kansas Cancer Center - Lee's Summit
🇺🇸Lee's Summit, Missouri, United States
The University of Kansas Cancer Center - North
🇺🇸Kansas City, Missouri, United States