Abstract P3-09-10: A phase II study of nivolumab in combination with cabozantinib for metastatic triple-negative breast cancer (mTNBC)

Background: Patients (pts) with mTNBC have a poor prognosis, and new therapies are needed. Cabozantinib is a multikinase inhibitor that blocks VEGF receptor 2, reduces myeloid-derived suppressor cells, and increases T cell infiltration, suggesting it may enhance the activity of the anti-PD-1 checkpoint blockade agent nivolumab. Here, we report the safety and efficacy of nivolumab plus cabozantinib in a phase II single-arm study in mTNBC pts. Methods: Eligible pts had metastatic breast cancer that was estrogen and progesterone receptor Results: From 12/15/2017 to 01/24/2019, 18 pts were enrolled into the first stage of the trial; one partial response was seen (ORR 5.6%; 95% CI: 0.3-29.4), and the study was closed to further accrual. The median age was 58y, all pts had ECOG PS 0, and 7 (38.9%) had liver metastases. The median number of prior cytotoxic therapies for mTNBC pts was 1 (range 0 to 3). Three pts had SD ≥24 weeks and two had progressive disease best response. The CBR was 22.2%. After a median follow up of 3.7 months, the median PFS was 4.4 months (95% CI: 1.9-12.8), and the median OS was 6.9 months (95% CI: 3.4-NR). All-cause adverse events occurred in 100% of pts (G3-4, 78%) including elevated liver enzymes (any 50%; G3-4 16.7%), hand-foot syndrome (any 38.9%; G3-4 16.7%), fatigue (any 38.9%; G3-4 11.1%), and hypothyroidism (any 33.3%; no G3-4). Of the 9 pts with available genomic data, none had tumor mutational burden ≥ 10 mutations per megabase. Updated data with TIL, PD-L1, whole exome sequencing and RNA-sequencing results will be presented. Conclusions: The combination of nivolumab plus cabozantinib was not associated with any unexpected adverse events, however, with an ORR of 5.6%, the study did not achieve its primary endpoint. Exploratory genomic and immunological correlative studies are ongoing. Clinical trial information: NCT03316586. Citation Format: Romualdo Barroso-Sousa, Lorenzo Trippa, Tianyu Li, Tanya E Keenan, Grace Winship, Chelsea Andrews, Wafa Osmani, Beth Overmoyer, Eric P Winer, Elizabeth A Mittendorf, Dan G Duda, Sara M Tolaney. A phase II study of nivolumab in combination with cabozantinib for metastatic triple-negative breast cancer (mTNBC) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-09-10.