Stay on Target: Reengaging Cancer Vaccines in Combination Immunotherapy

Abstract

Effective treatment of established tumors requires rational multicombination immunotherapy strategies designed to target all functions of the patient immune system and tumor immune microenvironment. While these combinations build on the foundation of successful immune checkpoint blockade antibodies, it is increasingly apparent that successful immunotherapy will also require a cancer vaccine backbone to engage the immune system, thereby ensuring that additional immuno-oncology agents will engage a tumor-specific immune response. This review summarizes ongoing clinical trials built upon the backbone of cancer vaccines and focusing on those clinical trials that utilize multicombination (3+) immuno-oncology agents. We examine combining cancer vaccines with multiple checkpoint blockade antibodies, novel multifunctional molecules, adoptive cell therapy and immune system agonists. These combinations and those yet to enter the clinic represent the future of cancer immunotherapy. With a cancer vaccine backbone, we are confident that current and coming generations of rationally designed multicombination immunotherapy can result in effective therapy of established tumors.

Keywords: adjuvant cytokines; cancer; clinical trial; combination therapy; immunotherapy; multifunctional; vaccine.

Figure 1

Quick efficacy seeking trial design trial schema. During part A, enrollment to arms 1.1 and 2.1A begins simultaneously. Arm 1.1 is a dose-finding arm for N-803 combined with Bintrafusp alfa (Bintra), open to all solid tumors. After arm 2.1A completes accrual and safety of the combination has been demonstrated, and N-803 dosing has been determined from arm 1.1, arm 2.2A begins accrual. After arm 2.2A completes accrual and safety of the combination has been demonstrated, enrollment to arm 2.3A begins. Each of the 3 arms enrolls a total of 13 patients during part A. At the completion of part A, if there is a positive safety signal and a positive efficacy signal in arm 2.1A, 2.2A, or 2.3A, part B will begin. To further assess efficacy, arms in which an activity signal was observed (arms 2.1B, 2.2B, and/or 2.3B) may expand to a total of 25 patients. During part B, patients are randomized among all open arms to avoid selection bias.