BeyondSpring Presents Poster Highlighting Preclinical and Clinical POC Immunomodulating Activity of Plinabulin Inducing Dendritic Cell Maturation and Re-sensitization in Immunotherapy Refractory Tumors when Combined with Radiation and PD-1/PD-L1 Inhibitors
November 07 2023 - 7:00AM
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, today 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 (NCT04902040) in six cancer
types.
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 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:
732Title: Immune Activation with Plinabulin
Enhances Anti-tumor response Combining Radiation with Immune
Checkpoint BlockadePresenter: Steven H. Lin,
MD/PhDSession: Poster Hall
Phase 1 Study RegimenAll 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
InformationBeyondSpring 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 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.
About BeyondSpringBeyondSpring
(NASDAQ: BYSI) is a global clinical-stage biopharmaceutical company
focused on developing innovative therapies to improve clinical
outcomes for patients with high unmet medical needs. The Company is
advancing its first-in-class lead asset, Plinabulin, as a direct
anti-cancer agent in various cancer indications and to prevent
chemotherapy-induced neutropenia. Its pipeline also includes three
preclinical immuno-oncology assets. Additionally, BeyondSpring’s
subsidiary, SEED Therapeutics, leverages a proprietary targeted
protein degradation (TPD) drug discovery platform and has an
initial R&D collaboration with Eli Lilly. Learn more by
visiting https://beyondspringpharma.com.
Investor
Contact:IR@beyondspringpharma.com
Media
Contact:PR@beyondspringpharma.com
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