Cabozantinib (CABO) plus durvalumab (DURVA) in patients (pts) with advanced urothelial carcinoma (UC) after platinum chemotherapy: safety and preliminary activity of the open-label, single-arm, phase 2 ARCADIA trial

Abstract

Both DURVA and CABO, an inhibitor of MET, AXL, and VEGFR, have shown single-agent activity in pts with UC. ARCADIA is a phase 2 study evaluating the combination of CABO with DURVA in pts with advanced UC or non-UC histology (NCT03824691). Herein we report the results of the interim safety analysis and the preliminary activity. Pts receive CABO 40 mg daily, orally, and are administered DURVA 1500 mg, intravenously, q28 days, until disease progression (PD, by RECIST 1.1) or onset of unacceptable toxicity. Key inclusion criteria are: ECOG-PS 0-1, UC and non-UC histology, failure of 1 or 2 platinum-based regimen for metastatic disease. Response is evaluated by RECIST criteria v.1.1 q2 cycles by CT and PET/CT scans. The primary endpoint of the study is OS. Other endpoints include safety (CTCAE v.4.03), objective response-rate (ORR), duration of response, progression-free survival. PD-L1 expression is assessed using with the Ventana SP142 assay. Next-generation sequencing tests (FoundationOne) on pre-therapy tumor samples is also performed As of May 20, 2020, 14 pts were enrolled with a median follow-up of 5 mo (range 1-8). Median age was 66 yrs (range 44, 74), 21% were male, and 60% had ECOG PS 1. 2 pts had pure neuroendocrine (NE) histology. Four pts (28%) had received 2 prior systemic anticancer therapies. Median tumor mutational burden (TMB) was 6 mut/Mb. Treatment-related AEs (TRAEs) occurred in 9 pts (64.3%), including 2 (14.3%) Grade 3 TRAEs, within the first 2 cycles. 3 pts (21.4%) discontinued CABO due to toxicity, none DURVA. The most common of any grade AEs were increased transaminases (35.7%) asthenia and diarrhea (28.6%), and hypertension (21.4%). In 10 response-evaluable pts, partial response (PR) was obtained in 2 (20%), ongoing at 6+ mo in one case harboring a driver RET (F116L) mutation. 0/2 NE tumors responded. CABO in combination with DURVA demonstrated encouraging clinical activity in pts with advanced UC with an acceptable safety profile. More mature results according to CABO-response biomarkers and histology will be presented.