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Found 1 Presentation For Request "773P"
773P - 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 II ARCADIA trial
- Laura Marandino (Candiolo, (TO), Italy)
Abstract
Background
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.
Methods
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 regimens for metastatic disease. The 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.5.0), objective response rate (ORR), duration of response, progression-free survival. PD-L1 expression is assessed using the Ventana SP142 assay. Next-generation sequencing tests (FoundationOne) on pre-therapy tumour samples are also performed.
Results
As of May 20, 2019, 14 pts were enrolled with a median follow-up of 5 mo (range 1-8). The 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. The median tumour mutational burden (TMB) was 6 mut/Mb. Treatment-related AEs (TRAEs) occurred in 9 pts (64.3%), all of Grade 1-2, within the first 2 cycles. One pt (7%) discontinued CABO due to toxicity, none DURVA. The most common TRAEs were asthenia (28.6%), diarrhea, creatinine increase and hypertension (all 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
Conclusions
CABO in combination with DURVA demonstrated encouraging clinical activity in pts with advanced UC with an acceptable safety profile. More mature results, with longer follow-up, according to CABO-related response biomarkers and histology will be presented.
Clinical trial identification
NCT03824691.
Legal entity responsible for the study
Andrea Necchi.
Funding
AstraZeneca; Ipsen.
Disclosure
All authors have declared no conflicts of interest.