Abstract 801TiP
Background
ABACUS and PURE-01 trials demonstrated the activity of single-agent atezolizumab and pembrolizumab respectively as neoadjuvant therapy for muscle-invasive urothelial carcinoma (MIUC), however, downstaging to non-muscle invasive disease was noted in only 50 percent of patients. Resistance to programmed death (PD) 1/L-1 antibodies is likely multifactorial including factors such as impaired dendritic cell maturation/function, infiltration of T-Regs, impaired T-cell priming, and T-cell trafficking in tumors. Cabozantinib is a tyrosine kinase inhibitor whose targets include MET, AXL, and VEGFR2. Cabozantinib has a unique immunomodulatory profile and has demonstrated clinical activity as monotherapy and in combination with PD-1/L1 antibodies in metastatic UC and renal cell carcinoma. We hypothesize that the combination of cabozantinib and atezolizumab in a neoadjuvant setting for MIUC would improve rates of pathologic downstaging compared to single-agent checkpoint inhibitors.
Trial design
ABATE(NCT04289779) is an open-label, single-arm study to assess the efficacy and safety of cabozantinib with atezolizumab as neoadjuvant therapy for cT2-T4aN0/xM0 MIUC. An estimated 38 patients will be enrolled and receive cabozantinib 40 mg PO daily with atezolizumab 1200mg every 3 weeks for a total duration of 9 weeks followed by radical cystectomy. Adults (≥18 years) with histologically confirmed, resectable UC who are either cisplatin-ineligible or decline cisplatin are eligible. Pts are required to have an ECOG PS of 0-2 and provide tumor tissue for PD-L1 analysis. Urothelial carcinoma should be the predominant component (≥ 50%). Previous systemic anticancer therapies for MIUC are not permitted. CT/MRI will be performed before investigational therapy and cystectomy. Primary endpoint is pathologic response rate defined as the absence of residual muscle-invasive cancer in the surgical specimen (< pT2). Secondary endpoints are safety and toxicity, pathologic complete response rate, and event-free survival. Exploratory endpoints include patient-reported outcomes and biomarkers. Accrual began May 2020. Clinical trial information: NCT04289779.
Clinical trial identification
NCT04289779.
Editorial acknowledgement
Legal entity responsible for the study
HCRN.
Funding
Exelixis and Genentech Exelixis and Genentech.
Disclosure
D. Kilari: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Exelixis. All other authors have declared no conflicts of interest.