In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. TPS4618-TPS4618
Kurzfassung:
TPS4618 Background: ABACUS and PURE-01 trials demonstrated the activity of single agent atezolizumab and pembrolizumab respectively as neoadjuvant therapy for muscle invasive bladder carcinoma (MIBC). However, downstaging to non-muscle invasive disease was noted in only 50 percent of patients. Resistance to programmed death (PD)- 1/L1 antibodies is likely to include factors such as impaired dendritic cell maturation/function, infiltration of T-Regs and myeloid derived suppressor cells, impaired T-cell priming and T-cell trafficking in tumors. Cabozantinib is a tyrosine kinase inhibitor which targets MET, AXL, MER, Tyro3 and VEGFR2. Cabozantinib has a unique immunomodulatory profile and has demonstrated clinical activity as monotherapy and in combination with PD-1/L1 antibodies in various solid tumors including urothelial cancer (UC), renal cell, castrate- resistant prostate and non-small cell lung cancer. We hypothesize that the combination of cabozantinib and atezolizumab as neoadjuvant therapy for MIBC would improve rates of pathologic downstaging compared to single-agent checkpoint inhibitors. Methods: ABATE is an open-label, single arm, multi-center study to assess the efficacy and safety of cabozantinib with atezolizumab as neoadjuvant therapy for cT2-T4aN0/xM0 MIBC. An estimated 42 patients will be enrolled to obtain 38 evaluable patients, and the study will have over 80% power to declare the investigational combination to be successful using a Bayesian evaluation at 90% posterior probability cutoff, if the response probability is 59%, i.e., 20% higher than the 39% response rate with the single agent atezolizumab. Eligible patients will receive cabozantinib 40 mg PO daily with atezolizumab 1200mg every 3 weeks for a total duration of 9 weeks (3 cycles) followed by radical cystectomy. Adults (≥18 years) with resectable MIBC who are either cisplatin-ineligible or decline cisplatin-based chemotherapy are eligible. Patients are required to have an ECOG PS of 0-2 and provide tumor tissue for PD-L1 expression analysis. UC should be predominant component (≥ 50%). Previous systemic anticancer therapies for MIBC 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 end points include patient-reported outcomes and outcome associations with biomarkers. Accrual began May 2020. Clinical trial information: NCT04289779.
Materialart:
Online-Ressource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/JCO.2022.40.16_suppl.TPS4618
Sprache:
Englisch
Verlag:
American Society of Clinical Oncology (ASCO)
Publikationsdatum:
2022
ZDB Id:
2005181-5
