1MO - An open-label, phase II trial of cabozantinib for advanced adrenocortical carcinoma

Background

Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with limited treatment options. This study aims to explore the role of carbozantinib in ACC management.

Methods

This is an investigator initiated, phase II study to evaluate the efficacy and safety of cabozantinib in patients with advanced ACC. Response to therapy was assessed objectively using The Response Evaluation Criteria in Solid Tumors (RECIST)v1.1. The primary end point was progression free survival (PFS) at 4 months (mo) (PFS4). Secondary endpoints included median PFS, overall response rate (ORR), median overall survival (OS), pharmacokinetic studies, and safety. Correlative tissue-based studies were performed.

Results

The study has fully accrued enrolling 18 patients with advanced ACC (8 females (44%). The median follow-up was 19.4 mo (range 2.9-45.6). The PFS4 was 72% (13/18), median PFS was 7.2 mo (95%CI: 3.3,9.2 mo). Of 18 patients, 16 had restaging with ORR including 2 partial response, 12 stable disease, and 2 progressive disease as best response; disease control rate was 78% (95% CI, 52% to 94%). The median PFS was 7.2 mo (95% CI, 3.3 mo to 9.2 mo), and the median OS was 23.9 mo (95% CI, 12.9, not reached). 13 patients (72.2%) had at least possible treatment-related grade 3 or 4 adverse events. Median day 29 pre-dose level of cabozantinib was 505mg/mL (range 279-1810). Correlative study analysis will be presented.

Conclusions

Cabozantinib use in patients with advanced ACC can provide sustained disease control with manageable safety profile in the majority of ACC patients.

Clinical trial identification

NCT03370718.

Editorial acknowledgement

Legal entity responsible for the study

University of Texas MD Anderson Cancer Center.

Funding

Exelixis.

Disclosure

M.T. Campbell: Financial Interests, Personal, Research Grant: Exelixis. C. Jimenez: Non-Financial Interests, Personal, Other, Research Support: Exelixis; Non-Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme, Progenics, Lantheus, Pfizer, HRA Pharma. A. Shah: Non-Financial Interests, Personal, Advisory Board: Pfizer, Exelixis, BMS; Non-Financial Interests, Personal, Other, Research Support: 4D Pharma, Eisai, EMD Serono. All other authors have declared no conflicts of interest.