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

Rhea-AI Summary

BeyondSpring Inc. announces dosing of first patient in Phase 2 trial for Extensive-Stage Small-Cell Lung Cancer with Pembrolizumab, Plinabulin, and EP, aiming to address unmet medical need. The trial evaluates the efficacy of this triple combination to improve progression-free survival rates. Plinabulin's role as a DC maturation agent in enhancing PD-1/PD-L1 blockade efficacy is highlighted.

Insights

Oncology Doctor

In the realm of oncology, the initiation of a Phase 2 trial assessing the efficacy of a novel therapeutic combination for Extensive-Stage Small-Cell Lung Cancer (ES-SCLC) is a significant development. ES-SCLC is characterized by high initial response rates to first-line treatments, yet the progression-free survival remains disappointingly brief. The combination of Pembrolizumab, a PD-1 inhibitor, with Plinabulin, a dendritic cell maturation agent and Etoposide/Platinum, aims to address the rapid progression observed in these patients by potentially enhancing the immune response and increasing the durability of treatment effects.

The integration of Plinabulin is particularly noteworthy, as dendritic cells play a important role in the presentation of tumor antigens and the initiation of T-cell mediated anti-tumor responses. The hypothesis is that by promoting dendritic cell maturation, Plinabulin may improve the efficacy of Pembrolizumab, which works by releasing the brakes on the immune system, allowing it to attack cancer cells more effectively. If successful, this treatment could lead to longer-lasting responses, thereby improving overall survival rates. The primary endpoint of the 12-month PFS rate will be important to determine the clinical benefit of this combination therapy.

Medical Research Analyst

From a research perspective, the study design and endpoints of the Phase 2 trial are of particular interest. The trial's primary endpoint, the 12-month progression-free survival (PFS) rate, is an important measure for understanding the potential long-term benefits of the treatment regimen. In previous studies, such as KEYNOTE-604, the 12-month PFS rate has been used as a benchmark for efficacy. The use of this endpoint in the current trial will allow for direct comparison with existing standards of care.

Furthermore, the trial's setting in Wuhan Union Hospital and its nature as an investigator-initiated trial (IIT) suggest a collaborative approach between the pharmaceutical company and clinical researchers. This type of partnership can accelerate the translation of preclinical findings into clinical practice. It is also indicative of a strategic move by BeyondSpring to leverage global research networks to validate their lead asset, Plinabulin, in combination with established cancer therapies.

Market Research Analyst

From a market perspective, the initiation of this trial is an essential step for BeyondSpring in terms of product development and potential market expansion. ES-SCLC represents a high unmet medical need and any advancement in treatment options could have a significant impact on patient outcomes and healthcare costs. The success of this trial could position BeyondSpring favorably in the competitive landscape of cancer therapeutics, particularly in the immuno-oncology space where the combination of chemotherapy and immunotherapy is becoming increasingly prevalent.

The potential market implications hinge on the trial outcomes. Positive results could lead to increased investor confidence, a rise in stock market valuation and interest from larger pharmaceutical companies for partnerships or acquisitions. In contrast, unfavorable results could pose risks to the company's valuation and future funding. As such, stakeholders will be monitoring this trial closely for indications of both clinical and commercial success.

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.

Investor Contact:
IR@beyondspringpharma.com 

Media Contact:
PR@beyondspringpharma.com 

FAQ

What is the purpose of the Phase 2 trial announced by BeyondSpring Inc.?

The Phase 2 trial aims to evaluate the efficacy and safety of Pembrolizumab, Plinabulin, and EP in first-line Extensive-Stage Small-Cell Lung Cancer.

What is the primary endpoint of the Phase 2 trial conducted by BeyondSpring Inc.?

The primary endpoint of the trial is the 12-month progression-free survival rate.

Who is the principal investigator for the Phase 2 trial conducted by BeyondSpring Inc.?

Dr. Xiaorong Dong, Deputy Director of the Oncology Research Department and Director of the Thoracic Oncology Department at Wuhan Union Hospital in China, is the principal investigator.

What is Plinabulin's role in the trial for Extensive-Stage Small-Cell Lung Cancer?

Plinabulin acts as a potent dendritic cell (DC) maturation agent, potentially enhancing the efficacy of PD-1/PD-L1 blockade and restoring sensitivity in patients who become resistant.

What was the key finding of the KEYNOTE-604 study mentioned in the press release?

The KEYNOTE-604 study revealed a 12-month progression-free survival rate of 13.6% in patients treated with pembrolizumab plus EP compared to 3.1% with placebo plus EP.