Bohac, Chet

AbstractBackgroundOutcomes data regarding advanced synovial sarcoma (SS) and myxoid/round cell liposarcoma (MRCL) are limited, consisting primarily of retrospective series and post hoc analyses of clinical trials.MethodsIn this multi‐center retrospective study, data were abstracted from the medical records of 350 patients from nine sarcoma centers throughout the United States and combined into a registry. Patients with advanced/unresectable or metastatic SS (n = 249) or MRCL (n = 101) who received first‐line systemic anticancer therapy and had records of tumor imaging were included. Overall survival (OS), time to next treatment, time to distant metastasis, and progression‐free survival (PFS) were evaluated using the Kaplan‐Meier method and Cox regression.ResultsAt start of first‐line systemic anticancer therapy, 92.4% of patients with SS and 91.1% of patients with MRCL had metastatic lesions. However, 74.7% of patients with SS and 72.3% of patients with MRCL had ≥2 lines of systemic therapy. Median OS and median PFS from first‐line therapy for SS was 24.7 months (95% CI, 20.9‐29.4) and 7.5 months, respectively (95% CI, 6.4‐8.4). Median OS and median PFS from start of first‐line therapy for MRCL was 29.9 months (95% CI, 27‐44.6) and 8.9 months (95% CI 4.5‐12.0).ConclusionsTo the best of our knowledge, this is the largest retrospective study of patients with SS and MRCL. It provides an analysis of real‐world clinical outcomes among patients treated at major sarcoma cancer centers and could inform treatment decisions and design of clinical trials. In general, the survival outcomes for this selected population appear more favorable than in published literature.

Abstract Purpose: LV305 is a modified, third-generation, nonreplicating, integration-deficient lentivirus-based vector designed to selectively transduce dendritic cells in vivo. LV305 induces expression of the New York Esophageal Squamous Cell Carcinoma-1 (NY-ESO-1) cancer testis antigen in dendritic cells, promoting immune responses against NY-ESO-1–expressing tumors. This phase I study evaluated the safety, immunogenicity, and preliminary efficacy of LV305 in patients with sarcoma or other solid tumors. Patients and Methods: Adults with previously treated, advanced, NY-ESO-1–positive solid tumors and limited tumor burden were eligible. LV305 was administered every 3 weeks by intradermal injection in four dose cohorts (Cohort 1: 108 vector genomes (vg) x 3 doses; Cohorts 1A, 2, and 3: 108 vg, 109 vg, 1010 vg x 4 doses). Results: Thirty-nine patients were enrolled: 3 patients each in Cohorts 1, 1A, and 2, and 30 patients in Cohort 3. No dose-limiting toxicities were observed. Tumor types included sarcoma (n = 24), ovarian (n = 8), melanoma (n = 6), and lung cancer (n = 1). All treatment-related adverse events were grade 1 or 2. Common treatment-related adverse events were fatigue (49%), injection site reactions (46%), and myalgia (21%). The disease control rate was 56.4% in all patients and 62.5% in sarcoma patients. One patient with synovial sarcoma achieved a partial response lasting >36 months. Anti–NY-ESO-1-specific CD4+ and/or CD8+ T cells were induced in 57% of evaluable sarcoma patients. Induction of an anti–NY-ESO-1 immune response was associated with improved 1-year survival in an exploratory analysis. Conclusions: This first-in-class, first-in-human study of LV305 demonstrated a favorable safety profile, induction of antigen-specific responses, and potential clinical activity in patients with advanced cancer.