This phase II trial tests how well cabozantinib in combination with pembrolizumab works in treating patients with adrenocortical cancer that has spread to nearby tissue or lymph nodes (locally advanced), that has spread from where it first started (primary site) to other places in the body (metastatic), or that cannot be removed by surgery (unresectable). Cabozantinib inhibits receptor tyrosine kinases, which are receptors commonly over-expressed by tumor cells. This may result in an inhibition of both tumor growth and blood vessel formation, eventually leading to a decrease in tumor size or extent in the body. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer and may interfere with the ability of tumor cells to grow and spread. Adding cabozantinib to pembrolizumab may be more effective at treating patients with adrenal cortical cancer than giving these drugs alone.
Male or female
Age >= 18 years
Eastern Cooperative Oncology Group (ECOG) performance status =< 2 ,Karnofsky >= 50%.
Metastatic disease or unresectable locally advanced disease.
Receipt of any type of small molecule kinase inhibitor including investigational kinase inhibitor within 2 weeks before first dose of study treatment
Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies
Receipt of any type of cytotoxic, biologic or other systemic anticancer therapy (including immunostimulatory agents or investigational agents) within 4 weeks or 5 half-lives of the drug (whichever is longer) before first dose of study treatment
Radiation therapy for bone metastasis within 2 weeks or any other radiation therapy within 4 weeks before first dose of study treatment. Systemic treatment with radionuclides within 6 weeks before first dose of study treatment. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible
Single group
Pembrolizumab
Biological/VaccineGiven IV
Biospecimen Collection
Procedure/SurgeryUndergo collection of blood samples
Cabozantinib S-malate
DrugGiven PO
Computed Tomography
Procedure/SurgeryUndergo CT
Magnetic Resonance Imaging
Procedure/SurgeryUndergo MRI
Overall response rate (ORR)
Overall response rate is defined as the proportion of patients with a complete response or partial response to treatment according to Response Evaluation Criteria in Solid Tumors version 1.1. Overall response rate will be estimated by the Clopper-Pearson method with 95% confidence intervals. Descriptive statistics on continuous data will include means, medians, standard deviations, and ranges, while categorical data will be summarized using frequency counts and percentages. Will explore whether the sample size can inform on the association between overall response rate and demographics or molecular biomarkers by Fisher's exact test -categorical variables and Wilcoxon rank-sum test -continuous variables, wherever appropriate this analysis is exploratory in nature.
Progression free survival
The Kaplan-Meier method will be used to estimate median event time with 95% confidence interval.
Overall survival
The Kaplan-Meier method will be used to estimate median event time with 95% confidence interval.
Incidence of adverse events
Evaluated according to the Common Terminology Criteria for Adverse Events version 5.0. Safety endpoints will be tabulated using frequency such as percent with at least one adverse event, percent for each grade, and percent with grade 3 or more adverse events.
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Emory University
Lead sponsor
National Cancer Institute (NCI)
Collaborator
