On November 7, 2023 BeyondSpring Inc. (NASDAQ: BYSI) ("BeyondSpring" or the "Company"), a global clinical-stage biopharmaceutical company focused on using a groundbreaking technology platform for drug discovery and developing innovative therapies to improve clinical outcomes for patients with high unmet medical needs, reported new data that translates preclinical proof-of-concept to clinical evidence of plinabulin’s immunomodulating activity (Press release, BeyondSpring Pharmaceuticals, NOV 7, 2023, View Source;utm_medium=rss&utm_campaign=beyondspring-presents-poster-highlighting-preclinical-and-clinical-poc-immunomodulating-activity-of-plinabulin-inducing-dendritic-cell-maturation-and-re-sensitization-in-immunotherapy-refractory-tumor [SID1234637121]). BeyondSpring and MD Anderson presented the data at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 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 (NCT04902040) in six cancer types.

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Based on preclinical models, where plinabulin plus radiation and anti-PD-1 antibody enhances dendritic cell (DC) activation, T-cell proliferation, and abscopal effect, a clinical study was initiated to test these findings. At the Phase 1 data cut-off (August 31, 2023), 19 heavily pretreated patients with 6 different cancers were exposed to plinabulin (30 mg/m2) after radiation initiation to an amendable lesion (3-6 hours apart) 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 (disease control rate) in non-irradiated tumor: In 10 immunotherapy-refractory patients of 6 different cancers (Hodgkin Lymphoma, NSCLC, SCCHN, Merkel Cell Carcinoma, RCC, Fibrolamellar HCC), plinabulin triple combination is safe and yields encouraging response with 80% disease control rate (3 PR, 5 SD, 2 PD).
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 (detectable 3 days later) in subsets of peripheral blood DC and monocytes in patients with clinical benefits (PR+SD).
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.
"There are severe unmet medical needs for cancer patients who progress on immunotherapies. We have been studying Plinabulin for 6 years, starting from preclinical proof-of-concept work in showing its DC maturation, abscopal effect and selective sequencing benefit with radiation, presented at the 2020 AACR (Free AACR Whitepaper) meeting, and now the successful clinical translation in the triple IO regimen and its notable high disease control rate in these hard-to-treat and multiple refractory cancers", Dr. Steven H. Lin, MD/PhD, professor of radiation oncology at MD Anderson commented. "These results are encouraging but preliminary. Based on the consistent mechanism in DC maturation in responding patients, this sets the stage for additional clinical studies of plinabulin/IO combinations in IO-refractory settings in a number of indications, including NSCLC and Hogkins Lymphoma".

SITC Conference Abstract Number: 732

Title: Immune Activation with Plinabulin Enhances Anti-tumor response Combining Radiation with Immune Checkpoint Blockade

Presenter: Steven H. Lin, MD/PhD

Session: Poster Hall

Phase 1 Study Regimen

All subjects received a triple combo treatment of Radiation Therapy (RT) + Plinabulin + Pembrolizumab or Nivolumab in Cycle 1, followed by the same anti-PD-1 antibody and plinabulin combo regimen in Cycle 2 and beyond until disease progression or development of unacceptable toxicity, withdrawal from study treatment, or discontinuation of this study.

A short course of local consolidative RT was administered in Cycle 1 starting from Day 1. Optional sequential RT may have been administered to target other untreated lesions at discretion of the treating doctor in Cycle 2 of any regimens.
Plinabulin was dosed on Day 1 and Day 4 of Cycle 1 of any anti-PD-1 regimen, and if optional RT was given in Cycle 2, Plinabulin was also given on Day 4 of Cycle 2. Plinabulin was given on Day 1 of Cycle 3 and thereafter. Anti-PD-1 antibody was dosed on Day 1 of every treatment cycle (also on Day 15 [Q4W] in case of regimen containing Nivolumab as Anti-PD-1 mAb).
Subjects received the same anti-PD-1/PD-L1 mAb they failed in the prior treatment.
Conference Call and Webcast Information

BeyondSpring will host a conference call and webcast today at 8:30 a.m. Eastern Time. The dial in numbers for the conference call are 1-877-407-0792 (U.S.) or 1-201-689-8263 (international). Please reference conference title: Clinical Significance of Plinabulin SITC (Free SITC Whitepaper) Presentation with PI Dr. Steven Lin from MD Anderson. A live webcast will be available on BeyondSpring’s website at www.beyondspringpharma.com under "Events & Presentations" in the Investors section. An archived replay of the webcast will be available for 30 days.