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

FLORHAM PARK, N.J., March 25, 2024 (GLOBE NEWSWIRE) -- 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 months^1,2. 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.

<sup>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.</sup>

About BeyondSpring
BeyondSpring (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.

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