2368P Activity of cabozantinib (CABO) plus durvalumab (DURVA) in patients (pts) with advanced non-urothelial-carcinoma variant histologies (VHs) or urothelial carcinoma (UC) after platinum-based chemotherapy: Interim results from the phase II ARCADIA trial

Combining multitargeted receptor tyrosine kinase inhibitor (TKI) with checkpoint inhibitors has shown synergistic effect in pts with UC due to the immunomodulatory propriety of VEGFR inhibitors. We investigated if the combination of CABO and DURVA in pts with advanced UC and non-UC histology (VHs) in a phase II study (NCT03824691). Herein the preliminary results of the interim analysis. In ARCADIA study, pts with UC or VHs recurred/progressed after failure of platinum-based CT were enrolled. Pts received CABO 40 mg daily orally and DURVA 1500 mg IV q28 days, until disease progression (PD, by RECIST 1.1) or unacceptable toxicity. The primary endpoint of the study was OS. Secondary endpoints: safety, objective response-rate (ORR), progression-free survival (PFS). Seventy-one pts were enrolled from 11/2019 to 04/2023: this interim analysis was performed after obtaining at least one post-baseline tumor assessment data from 62 pts. The median follow-up was 21.9 mos (interquartile [IQ] range: 15.6 – 27.3 mos): 27.4% female, median age 64 yrs (IQ range: 55– 70 yrs), 21 pts (34%) had a pure/predominant non-UC VH: 10 (48%) squamous differentiation/sarcomatoid, 5 (24%) adenocarcinoma, 4 (19%) small-cell neuroendocrine, 1 (5%) clear-cell, and 1 nested VH (5%). In 62 pts, 12 (19%) CR and 10 (16%) PR were obtained, the ORR being 35.5% (95% CI, 23.7 – 48.7) and disease control rate was 71.0% (95% CI, 58.1 – 81.8). In VHs cohort, the ORR was 42.9% (95% CI, 21.8 – 66.0). Median PFS was 7.4 mos (95% CI, 4.9 – 26.3 mos) and median OS was 13.1 mos (95% CI, 7.23 – NA). The duration of response (DOR) was 8.18 mos (95% CI, 4.0 – 21.2); 42 pts (67.7%) of 62 pts had all-grade treatment-related adverse events (trAE): among them, 7 pts (16.7%) reported grade ≥ 3 trAE. Dose-reductions of CABO were needed in 26 pts (41.9%). No treatment-related deaths were reported. CABO in combination with DURVA showed promising preliminary activity with a manageable safety profile in pts with advanced in VHs and UC after previous chemotherapy exposure. More mature results with longer follow-up will be presented.