Abstract B117: Phase II study of brentuximab vedotin and bevacizumab in GCT

Abstract

Abstract Background: Outcomes in refractory germ cell tumors (GCT) after failure of platinum-based chemotherapy are poor with complete responses with salvage chemotherapy being rare and short-lived. Patients progressing after ≥2 lines of chemotherapy have a dismal prognosis and die from disease. Novel therapies and combination strategies are urgently needed. Cluster of Differentiation antigen-30 (CD30) is expressed in embryonal carcinoma, implicating CD-30 as a target in CD-30+ GCT. Brentuximab vedontin (BV) is an antibody-drug conjugate that combines mono-methyl auristatin E (MMAE) with a CD-30 specific monoclonal antibody, and has shown promising activity in CD30+ GCT. VEGF is involved in tumor development, angiogenesis, and metastasis in GCT, and anti-VEGF monoclonal antibody, bevacizumab, has shown activity in GCT. BV and bevacizumab may be synergistic in refractory CD30+ GCT with no potentially overlapping toxicities. Methods: This is a multicenter phase II study of BV and bevacizumab for the treatment of refractory CD-30+ GCT after disease progression on imaging and/or tumor marker progression with serially rising AFP or bHCG. Patients must have received ≥ 2 lines of platinum-based chemotherapy, but only 1 prior line will be allowed if the patient is ineligible or refuses further platinum-based chemotherapy. For primary mediastinal GCT, failure of 1st-line chemotherapy is allowed. Expression of CD-30 (1% or more) in archival or fresh biopsy is required for eligibility. Primary objective is objective response rate. Secondary objectives are safety and tolerability, PFS, and OS. Exploratory objectives include correlation of clinical outcomes with CD-30 expression in tumors and blood and VEGF level in blood, and presence of circulating tumor cells (CTCs) and correlation with clinical outcomes. BV and bevacizumab will be given every 21 days at doses of 1.8 mg/kg and 15mg/kg, respectively, until disease progression or unacceptable toxicity; intrapatient dose reduction of BV to 1.2 mg/kg will be allowed. A total of 21 patients will be enrolled and results from this study will provide an insight into the safety and efficacy of this combination in refractory CD-30+ GCT. (NCT02988843) Citation Format: Shilpa Gupta, Benjamin L. Maughan. Phase II study of brentuximab vedotin and bevacizumab in GCT [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr B117.