title: Combination immunotherapy: a road map.
abstract: Cancer immunotherapy and in particular monoclonal antibodies blocking the inhibitory programed cell death 1 pathway (PD-1/PD-L1) have made a significant impact on the treatment of cancer patients in recent years. However, despite the remarkable clinical efficacy of these agents in a number of malignancies, it has become clear that they are not sufficiently active for many patients. Initial evidence, for example with combined inhibition of PD-1 and CTLA-4 in melanoma and non-small cell lung cancer (NSCLC), has highlighted the potential to further enhance the clinical benefits of monotherapies by combining agents with synergistic mechanisms of action. In order to address the current progress and consider challenges associated with these novel approaches, the Society for Immunotherapy of Cancer (SITC) convened a Combination Immunotherapy Task Force. This Task Force was charged with identifying and prioritizing the most promising prospects for combinatorial approaches as well as addressing the challenges associated with developing these strategies. As a result of the extensive clinical benefit and tolerable side effects demonstrated with agents inhibiting the PD-1 pathway, an overview of current evidence to support its promising potential for use as a backbone in combination strategies is presented. In addition, key issues in the development of these strategies including preclinical modeling, patient safety and toxicity considerations, clinical trial design, and endpoints are also discussed. Overall, the goal of this manuscript is to provide a summary of the current status and potential challenges associated with the development and clinical implementation of these strategies.
authors.affiliation: Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Avenue, Dana540C, Boston, MA 02215 USA.
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Ott
authors.affiliation: Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Avenue, Dana540C, Boston, MA 02215 USA.
authors.forename: F Stephen
authors.initials: FS
authors.lastname: Hodi
authors.affiliation: Rutgers Cancer Institute of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08901 USA.
authors.forename: Howard L
authors.initials: HL
authors.lastname: Kaufman
authors.affiliation: MacroGenics, Inc., 9640 Medical Center Drive, Rockville, MD 20850 USA.
authors.forename: Jon M
authors.initials: JM
authors.lastname: Wigginton
authors.affiliation: Memorial Sloan Kettering Cancer Center, 1275 York Avenue, Z-1503, New York, NY 10065 USA.
authors.forename: Jedd D
authors.initials: JD
authors.lastname: Wolchok
mesh_terms: D000818:Animals; D000074322:Antineoplastic Agents, Immunological / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D006801:Humans; D007167:Immunotherapy / Q000009:adverse effects; D009369:Neoplasms / Q000188:drug therapy*
chemical_list: D000074322:Antineoplastic Agents, Immunological
keywords: Checkpoint inhibitors; Clinical trial; Combination; Endpoints; Immunotherapy; Preclinical models