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

Background

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.

Methods

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).

Results

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.

Conclusions

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.

Clinical trial identification

NCT03824691.

Editorial acknowledgement

Legal entity responsible for the study

Fondazione IRCCS Istituto Nazionale dei Tumori.

Funding

Ipsen, AstraZeneca, Fondazione IRCCS Istituto Nazionale dei Tumori.

Disclosure

P. Giannatempo: Financial Interests, Personal and Institutional, Advisory Board: Pfizer, Astellas, Janssen, msd, merk. G. Baciarello: Financial Interests, Personal, Advisory Board: Gensenta; Financial Interests, Institutional, Steering Committee Member: Bayer; Non-Financial Interests, Principal Investigator: Roche, Eli Lilly, MSD; Non-Financial Interests, Member: ASCO. S. Buti: Financial Interests, Personal, Advisory Board: BMS, Pfizer, MSD, MSD, Ipsen, AstraZeneca, Pierre-Fabre, Novartis; Financial Interests, Personal, Invited Speaker: BMS, MSD, Ipsen, AstraZeneca, Novartis; Financial Interests, Institutional, Local PI: BMS, Ipsen, AstraZeneca; Financial Interests, Institutional, Coordinating PI: BMS, MSD; Financial Interests, Institutional, Research Grant: Novartis; Non-Financial Interests, Other, Member of panel for kidney cancer guidelines: AIOM (Italian Association of Medical Oncology); Non-Financial Interests, Other, member and coordinator of the “Rare Tumors” group: Meet-URO group (Italian Network For Research In Urologic-Oncology). R. Iacovelli: Financial Interests, Personal, Advisory Board: BMS, MSD, Janssen, Astellas, Ipsen, Pfizer, Bayer, Sanofi, Eisai; Financial Interests, Personal, Invited Speaker: Recordati; Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Institutional, Local PI: MSD, Seagen; Non-Financial Interests, Member: AIOM. E. Verzoni: Financial Interests, Personal, Advisory Board: Msd, Janssen, AstraZeneca; Financial Interests, Personal, Invited Speaker: BMS, Astellas, Ipsen, Pfizer; Non-Financial Interests, Principal Investigator: MSD, Ipsen, Astellas, Janssen, Lilly, Pfizer. G. Procopio: Financial Interests, Personal, Advisory Board, consultant fees: Astellas, AstraZeneca, Bayer, BMS, Janssen, Ipsen, Merck, MSD, Novartis, Pfizer; Financial Interests, Institutional, Research Grant, research funding for no profit clinical trial: Ipsen. A. Necchi: Financial Interests, Institutional, Research Grant: Merck, AstraZeneca, Ipsen, BMS, Gilead; Financial Interests, Personal, Steering Committee Member: Roche, Janssen, Bayer, Astellas, AstraZeneca, Merck, Clovis Oncology; Financial Interests, Coordinating PI: Incyte; Financial Interests, Local PI: Pfizer; Non-Financial Interests, Leadership Role: Global society of Rare Genitourinary Tumors (GSRGT). All other authors have declared no conflicts of interest.