Assessments and endpoints
tumor, DLTs, toxicity, lymphopenia, Tumors, Cancer
ADVERSE EVENT, TUMOR, MELANOMA, ADVERSE EVENT, LYMPHOPENIA, TUMORS, CANCER
Adverse events and DLTs were assessed based on the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03. AEs were assessed from the time of initiating study treatment through 30 days after cessation of study treatment. DLTs were defined as any grade ≥ 3 toxicity related or possibly related to V937 with onset on or before the day 92 visit, except for lymphopenia, which was not considered a DLT.Disease status was assessed every 6 weeks by computed tomography or magnetic resonance imaging. Response and progression were evaluated using immune-related response criteria derived from modified World Health Organization criteria, as previously described [Optional melanoma tumor biopsy samples were obtained at screening by incisional, excisional, or punch biopsy; archival tissue could be used in place of a fresh biopsy sample. Tumors selected for biopsy could have been target or nontarget lesions; target lesions had to be > 20 mm in total size, and sample collection could not affect the longest diameter for purposes of tumor assessment. Biomarker analyses performed on these tumor samples included NanoString-based interrogation of gene expression with the PanCancer IO 360™ Panel (NanoString, Seattle, WA, USA) and multiplex IHC (Supplementary Table S1). In addition, Luminex cytokine analysis was performed on day 1 and day 29 paired serum samples with a 48-plex human Cytokine/Chemokine/Growth Factor Panel A (Millipore Sigma, Burlington, MA) analyzed on a Luminex 2000 analyzer (Luminex Corporation, Austin, TX). Serum V937 levels, based on polymerase chain reaction, were assessed during the first 2 years of treatment (at every study visit through week 46, at week 52, and every 12 weeks thereafter). Anti-V937 antibody titers were also evaluated during the first 2 years of treatment (at baseline, week 4, week 22, every 3 weeks through week 46, at week 52, and every 12 weeks thereafter).The primary endpoints were the occurrence of AEs, serious AEs, and DLTs. Secondary endpoints were ORR, PFS, OS, and duration of response. Biomarkers were an exploratory endpoint.