BeyondSpring presents new data on plinabulin’s immunomodulating activity

BeyondSpring announced new data that translates preclinical proof-of-concept to clinical evidence of plinabulin’s immunomodulating activity. BeyondSpring and MD Anderson presented the data at the Society for Immunotherapy of Cancer’s, SITC, 38th Annual Meeting on Nov 4th in San Diego, CA on an open-label, Phase 1 basket study at The University of Texas MD Anderson Cancer Center in cancer patients after progressing on PD-1, PD-L1 and/or CTLA-4 antibodies in six cancer types. Based on preclinical models, where plinabulin plus radiation and anti-PD-1 antibody enhances dendritic cell activation, T-cell proliferation, and abscopal effect, a clinical study was initiated to test these findings. At the Phase 1 data cut-off, 19 heavily pretreated patients with 6 different cancers were exposed to plinabulin after radiation initiation to an amendable lesion plus anti-PD-1 antibody, including pembrolizumab or nivolumab. 11 out of 14 patients eligible for efficacy assessment per RECIST criteria and had measurable target lesion responses in the non-irradiated tumor lesion. Disease control rate evaluates the tumor reduction in non-irradiated tumor to assess abscopal effect from immune agents. 80% DCR in non-irradiated tumor: In 10 immunotherapy-refractory patients of 6 different cancers, plinabulin triple combination is safe and yields encouraging response with 80% disease control rate. Durable Response in heavily pre-treated patients: 2 Hodgkin’s lymphoma patients who progressed after 12 or 16 prior lines of therapy respectively, had durable responses with one PR and one SD. These patients continued treatment after data cutoff. DC maturation in responding patients: Plinabulin administered after radiation initiation induces an early systemic immune response in subsets of peripheral blood DC and monocytes in patients with clinical benefits. Plinabulin mediates GEF-H1-dependent immune activation in responding patients: In patients with PR+SD, tumor scRNAseq analysis indicates GEF-H1-dependent immune activation in subsets of DC and monocyte-derived macrophages. Such activation was not seen in patients with PD. Additional biomarker analyses at baseline and post-treatment are underway.