Quick efficacy seeking trial (QuEST1): a novel combination immunotherapy study designed for rapid clinical signal assessment metastatic castration-resistant prostate cancer

Advances in immunotherapy utilizing immune checkpoint inhibitors (ICIs) have transformed the treatment landscapes of several malignancies in recent years. Oncologists are now tasked with extending these benefits to a greater number of patients and tumor types. Metastatic castration-resistant prostate cancer (mCRPC) infrequently responds to ICIs, while the cellular vaccine approved for mCRPC, sipuleucel-T, provides a 4-month survival benefit but does not produce clinical responses as monotherapy. However, many novel and generally well-tolerated immune oncology agents with potential for immune synergy and/or additive effects are undergoing clinical development. This availability presents opportunities to develop adaptive-design combination clinical trials aimed to generate, expand, and facilitate antitumor immune responses. Here we describe a currently accruing phase I/II trial (NCT03493945) testing a brachyury-targeted antitumor vaccine, TGF-β TRAP/anti-PD-L1 antibody, an IL-15 agonist, and an IDO1 inhibitor in mCRPC. Trial registration: This trial (NCT03493945) was registered in National Clinical Trials on April 11th 2018.