Metronomic vinorelbine combined with durvalumab plus tremelimumab dual immunotherapy in patients with metastatic prostate cancer

Immune checkpoint inhibitors (ICI) are a class of immunotherapy drugs that have shown significant success in treating various types of cancers. However, their effectiveness in treating prostate cancer (PC) has been more challenging due to an immunosuppressive tumor microenvironment. Low-dose metronomic chemotherapy have immunomodulatory properties that could enhance immunotherapy and is well-tolerated. MOVIE was a phase 1/2 multi-cohort study with a Bayesian design that evaluated the antitumor activity and safety of metronomic vinorelbine with durvalumab plus tremelimumab. Here, we report the results of the PC cohort during phase 2. Fifteen patients with locally advanced or metastatic PC, resistant to conventional therapies, presenting a measurable disease according to RECISTv1.1, and a performance status (PS)≤1, received metronomic oral vinorelbine 40mg three times a week, and durvalumab 1500mg plus tremelimumab 75mg intravenously at day 1 of 28-day cycles. Primary endpoint was the clinical benefit rate (CBR) evaluated using a Bayesian design. Secondary endpoints included safety, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Mean estimated CBR according to a non-informative prior distribution was 12.5% (95% credible interval: 1.7-31.9). One patient achieved PR leading to an ORR of 7.7%, and 4 SD<24 weeks. Median PFS was 1.9 months (95% confidence interval [CI]: 1.7-3.8), and median OS 5.4 months (95%CI: 2.4-12.2). Most frequent treatment-related G≥3 AEs were anemia (13.3%) for vinorelbine, and colitis (20.0%) and diarrhea (13.3%) for ICI. One treatment-related G5 AE (sepsis) was observed. The study outcomes highlighted the complexities of treating advanced PC with ICI, even when combined with metronomic vinorelbine.