BeyondSpring Announces First Patient Dosed with Pembrolizumab, Plinabulin Plus Etoposide/Platinum in a Phase 2 Investigator-initiated Study of First-Line Extensive-Stage Small-Cell Lung Cancer
March 25 2024 - 7:00AM
BeyondSpring Inc. (NASDAQ: BYSI) (“BeyondSpring”
or the “Company”), a clinical-stage global biopharmaceutical
company focused on developing innovative cancer therapies, today
announced that the first patient has been dosed in a Phase 2
investigator-initiated trial (IIT) with Pembrolizumab, Plinabulin,
BeyondSpring’s lead asset, plus Etoposide/Platinum (EP) for
first-line (1L) Extensive-Stage Small-Cell Lung Cancer
(ES-SCLC) [NCT05745350].
Current treatment for first-line ES-SCLC
includes EP and EP plus PD-L1 antibodies. Although the objective
response rate (ORR) is high (around 60-65%), median progression
free survival (PFS) remains low (< 6 months), with median
overall survival at 10-13 months1,2. Therefore, 1L ES-SCLC remains
a serious unmet medical need.
Plinabulin, a potent dendritic cell (DC)
maturation agent3, has been studied in a triple combination with
various immuno-oncology agents and chemotherapy or radiation, with
the potential to enhance the efficacy of PD-1/PD-L1 blockade and
restore sensitivity in patients who become resistant [NCT04902040,
NCT05599789]. Preliminary re-sensitization data in PD-1/PD-L1
antibody failed patients in 8 cancer types [NCT04902040, IIT at MD
Anderson] corresponding response with Plinabulin DC maturation was
presented at SITC conference in Nov 20234.
This Phase 2 trial will evaluate the efficacy
and safety of Pembrolizumab, Plinabulin plus EP in 1L ES-SCLC. The
study5 is conducted in Wuhan Union Hospital in China, with Dr.
Xiaorong Dong, Deputy Director of the Oncology Research Department
and Director of the Thoracic Oncology Department, as the principal
investigator. Patients enrolled are receiving the following
interventional treatments. The primary endpoint is the
12-month PFS rate.
- Pembrolizumab 200 mg IV every 3
weeks (Q3W) on Day 1
- Etoposide 100 mg/m2 IV Q3W on Days
1, 2, and 3
- Carboplatin AUC 5 IV Q3W on Day 1
or Cisplatin 75 mg/m2 IV Q3W on Day 1
- Plinabulin 30mg/m2 IV Q3W on
Day 1
“Although the current therapies in first-line
ES-SCLC, including PD-L1 antibody and EP combination have had a
high ORR, the duration of response is still short with median PFS
of < 6 months. KEYNOTE-604 study revealed that 12-month
PFS rate in patients with pembrolizumab plus EP is 13.6% vs. 3.1%
with placebo plus EP. According to Dr.
Mellman’s recent review on cancer immunity cycle6, mature DC is
critical for the maintenance of cytotoxic T-cell response against
the tumor. By adding Plinabulin, a potent DC maturation agent, to
pembrolizumab plus EP, could potentially enable a durable response
and improve PFS. This combination study represents an important
step forward to address this unmet medical need. I am eager to
evaluate this treatment in clinical settings, ensuring that
cutting-edge, advanced therapies are translated to cancer care
worldwide,” said Dr. Xiaorong Dong, principal investigator for the
study.
“We are pleased to start this second IIT study
with Merck. Our first Merck IIT study initiated in March 2023 was
in 2L/3L NSCLC cancer patients who had failed prior PD-1/PD-L1
blockade [NCT05599789]. We believe in the collateral sensitivity
and efficacy potential of this triple IO combination in both front
and later lines of cancer treatment. Plinabulin’s unique DC
maturation mechanism may pose to be the ‘bridge’ between tumor
neo-antigen generation from chemotherapy, and T cells action
enabled by PD-1 antibodies. Potential improvements in both
duration-of-response and quality-of-life could translate into
overall survival benefit. Every moment of a cancer patient’s life
is valuable, and our primary goal is to discover innovative
treatment strategies that prolong their lives,” added Dr. Lan
Huang, Co-Founder, Chairman and CEO at BeyondSpring.
References:1. Horn, L.,
Mansfield, A.S., Szczesna, A., et al. First-line Atezolizumab plus
Chemotherapy in Extensive-Stage Small-Cell Lung Cancer. N Engl J
Med. 2018;379(23):2220–9. 2. Paz-Ares L, Dvorkin M, Chen Y, et al.
Durvalumab plus platinum–etoposide versus platinum–etoposide in
first-line treatment of extensive-stage small-cell Lung cancer
(CASPIAN): a randomised, controlled, open-label, phase 3 trial. The
Lancet. 2019; 394(10212):1929–39. 3. Kashyap, A.S.,
Fernandez-Rodriguez, L., Zhao, Y., et al. GEF-H1 Signaling upon
Microtubule Destabilization Is Required for Dendritic Cell
Activation and Specific Anti-tumor Responses. Cell Rep 2019;
28(13): 3367-80.e8.4.
Lin, S.H., Cohen, E., Li, Z., et al
732 Immune activation with plinabulin enhances anti-tumor response
combining radiation with immune checkpoint blockade. Journal for
ImmunoTherapy of Cancer 2023;11:doi:
10.1136/jitc-2023-SITC2023.0732.5. An Open-Label, Single-Arm, Phase
II Study of Pembrolizumab, Plinabulin Plus Etoposide and Platinum
as First-Line Therapy for Extensive-Stage Small-Cell Lung Cancer.
Clinicaltrials.gov identifier: NCT05745350. Conducted by Wuhan
Union Hospital. 6. Mellman, I., Chen, D.S., Powles, T. &
Turley, S.J. The cancer-immunity cycle: Indication, genotype, and
immunotype. Immunity. 2023; 56(10): 2188-2205.
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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