A phase 1b study of cabozantinib and nivolumab with abiraterone (CABIOS) in metastatic castration-sensitive prostate cancer (mCSPC): Updated safety, efficacy, and immunologic findings.

186 Background: Standard of care for mCSPC typically includes androgen deprivation (ADT) with novel hormonal agents +/- docetaxel. CABIOS is a phase Ib single-arm trial of cabozantinib + nivolumab + abiraterone/prednisone (cabo, nivo, abi/pred) in mCSPC (NCT04477512). Preliminary safety and efficacy data were previously reported. Methods: Eligible patients (pts) had de novo or recurrent mHSPC with < 12 weeks ADT prior to enrollment, ECOG 0-1, and adequate end organ function. Further details on trial design were previously reported. The primary endpoint is safety and tolerability. Secondary endpoints include overall survival (OS), progression free survival (PFS), PSA response, and failure-free survival (FFS; defined as any one of clinical, PSA, or radiographic progression, or new treatment start). Exploratory analyses include CyTOF of peripheral blood and multiplex serum cytokine ELISA. Results: The trial is closed to accrual. 18 pts enrolled between 2/2021 and 3/2023 received treatment and are included in the analysis. Median follow-up is 32 months. There were no dose-limiting toxicities (DLTs). Gr 3-4 treatment related adverse events (TRAEs) occurred in 8 pts. The most common serious TRAEs were AST/ALT elevation (4), diarrhea (3), and hypertension (3). Treatment continued for or beyond study duration (two years) in 6 pts. Treatment was stopped in 12 pts due to adverse events (6), progression (5), and patient preference (1). Median OS and PSA PFS have not been reached. Nine of 18 pts had an FFS event at a median of 15.6 months compared with a median censored FFS of 32.2 months to-date in the remaining pts. CyTOF analyses of peripheral blood revealed a significant increase in effector cytotoxic CD8+ T-cells, total NK cells and CD16 hi cytotoxic NK cells post- compared with pre-treatment. Conversely, regulatory CD4+ and CD8+ T-cell as well as Th17 cell populations were significantly decreased in peripheral blood post-treatment. Furthermore, a marked reduction in free-active TGF-β and soluble LAG3 were observed in serum post vs. pre-treatment. We compared pre-to-post fold changes in these populations between patients who have and have not experienced treatment failure (FFS). Early treatment failure was associated with reduced innate lymphoid cells and increased total B-cells. Conclusions: Here, we present updated clinical and immune correlative findings of the first trial of cabozantinib in combination with nivolumab in mCSPC patients receiving ADT and abi/pred. Overall, the trial showed acceptable safety/tolerability with no DLTs. Grade 3+ TRAEs were seen in 44% of patients. Correlative data suggest a favorable peripheral immunomodulation by the treatment combination with a reduction in suppressive soluble factors and increase in effector immune populations. Future studies will evaluate the tumor microenvironment. Clinical trial information: NCT04477512 .