BeyondSpring Presents Final Data Analysis of DUBLIN-3 Phase 3 Study in 2L/3L EGFR Wild-type NSCLC at ESMO Congress 2024

Rhea-AI Summary

BeyondSpring (NASDAQ: BYSI) presented final data on the DUBLIN-3 Phase 3 study at ESMO Congress 2024, showing significant improvements in overall survival, progression-free survival, and objective response rate for the plinabulin/docetaxel combination in 2L/3L EGFR wild-type NSCLC patients. The combination demonstrated a favorable benefit/risk ratio over docetaxel alone, including:

1. >80% relative reduction in Grade 4 neutropenia
2. Reduced use of G-CSF
3. Improved quality of life
4. Significant reduction in cycle-adjusted serious adverse events

The study suggests this combination could be a new option for second or third-line NSCLC patients without driver mutation, addressing an unmet medical need.

Positive

• Significant improvement in overall survival, progression-free survival, and objective response rate
• >80% relative reduction in Grade 4 neutropenia (p<0.001)
• Reduced use of granulocyte-colony stimulating factor (G-CSF) in all cycles
• Improved quality-of-life based on Q-TWiST data
• Significant reduction in cycle-adjusted serious adverse events (SAE)

Negative

• Plinabulin induced mostly asymptomatic transient hypertension
• Plinabulin induced GI side effects, including nausea, vomiting, and diarrhea

Insights

Oncology Expert

This phase 3 study presents significant findings for EGFR wild-type NSCLC patients. The plinabulin/docetaxel combination showed improved overall survival, progression-free survival and objective response rate compared to docetaxel alone. Notably, there was a 81% reduction in Grade 4 neutropenia and improved quality of life. This is important as neutropenia often limits docetaxel's use.

The reduction in G-CSF use and fewer hospital admissions due to febrile neutropenia are clinically significant, potentially reducing treatment costs and complications. The manageable side effects, including transient hypertension and GI issues, suggest a favorable risk-benefit profile. This combination could become a new standard for 2nd/3rd line treatment in this patient population, addressing an unmet medical need.

Medical Research Analyst

The DUBLIN-3 study stands out among recent phase 3 trials in 2L/3L EGFR wild-type NSCLC. While six recent studies failed to show overall survival benefits compared to docetaxel and two others (LUNAR and TROPION-Lung01) showed mixed results, DUBLIN-3 demonstrated clear improvements in multiple endpoints.

The multicenter, international design (58 centers across Australia, China and the USA) and large sample size (559 patients) lend credibility to the results. The publication in Lancet Respiratory Medicine, a high-impact journal, further validates the study's importance. The combination's efficacy, coupled with its safety profile and quality of life improvements, positions it as a potentially practice-changing treatment option in this difficult-to-treat patient population.

Financial Analyst

This clinical data could significantly impact BeyondSpring's market position. The positive results in a large, difficult-to-treat patient population address a substantial market need. If approved, the plinabulin/docetaxel combination could capture a significant share of the 2L/3L EGFR wild-type NSCLC market.

The reduced need for G-CSF and fewer hospitalizations could translate to cost savings for healthcare systems, potentially aiding in reimbursement negotiations. The improved safety profile might lead to broader adoption among oncologists. However, investors should note that regulatory approval and market adoption processes can be lengthy and uncertain. The company's ability to navigate these next steps will be important for realizing the commercial potential of this promising treatment combination.

Plinabulin/Docetaxel Combination Demonstrated Favorable Benefit/Risk Ratio over Docetaxel Alone: Significant Improvement in Overall Survival, Progression Free Survival, and Objective Response, with additional Significant Reduction of Grade 4 Neutropenia (>80% relative reduction), and Improved Patients’ Quality of Life

FLORHAM PARK, N.J., Sept. 16, 2024 (GLOBE NEWSWIRE) -- BeyondSpring Inc. (NASDAQ: BYSI) (“BeyondSpring” or the “Company”), a clinical-stage global biopharmaceutical company developing innovative cancer therapies, presented final data on Dublin-3 study (2L/3L EGFR wild-type NSCLC) focusing on safety outcomes on September 14, 2024 at European Society for Medical Oncology (ESMO) Congress 2024 in Barcelona, Spain. Full data on Dublin-3 study was published on September 9, 2024 in the Lancet Respiratory Medicine (https://doi.org/10.1016/S2213-2600(24)00178-4).

Docetaxel remains the standard of care for patients with 2L/3L NSCLC without targetable alterations despite severe neutropenia (>40%) that greatly impair patients’ quality of life. Six recent phase 3 studies in patients with EGFR wild-type NSCLC who were previously treated with immune checkpoint inhibitors failed to show overall survival (OS) benefit compared with docetaxel (SAPPHIRE, LEAP-008, CONTACT01, EVOKE-01, CARMEN-LC03, and CANOPY-2). Two phase 3 studies (LUNAR and TROPION-Lung01) showed positive but mixed outcomes compared with docetaxel.

The DUBLIN-3 study was a multicenter, single-blinded, randomized controlled trial that enrolled patients from 58 medical centers across Australia, China, and the USA. 559 patients with epidermal growth factor receptor (EGFR) wild-type NSCLC were randomly assigned (1:1) to receive either docetaxel and plinabulin (n=278) or docetaxel and placebo (n=281). The plinabulin/docetaxel combination significantly improved overall survival (OS), progression-free survival (PFS), and objective response rate (ORR) compared to docetaxel alone. (Click here for related press release.)

This poster presentation focused on plinabulin and docetaxel combination safety vs. docetaxel alone, as shown below:

• The combination is well tolerated: Similar percentages of patients experienced ≥1TEAE (treatment emergent adverse events); 99.6% in the combination arm and 99.3% in the docetaxel arm. There was less grade 4 TEAE in the combination arm (19.0%) vs. 42.8% in the docetaxel arm.
• The combination had >80% relative reduction in Grade 4 neutropenia (p<0.001): The combination arm had a 5.3 % Grade 4 neutropenia in Cycle 1 Day 8 compared to 27.8% in docetaxel alone (81% reduction, p<0.0001). The combination arm had a 5.1 % Grade 4 neutropenia in all cycles Day 8 compared to 33.6% in docetaxel alone (85% reduction, p<0.0001). In addition, hospital admission due to febrile neutropenia was lower in the combination arm (7 [2.6%] patients) vs. docetaxel arm (14 [5.0%] patients).
• The combination had reduced use of granulocyte-colony stimulating factor (G-CSF) in all cycles: Post-hoc analysis showed reduced G-CSF use in the combination arm (152 [56%] patients) vs. docetaxel arm (182 [66%] patients) and at cycles 1 to 4.
• The combination had improved quality-of-life (QoL) based on Q-TWiST data: Exploratory analysis showed better QoL based on Q-TWiST in the combination arm, with a clinically meaningful relative gain to the docetaxel arm of 18.5%(p=0.0393).
• The combination had a significant reduction in cycle-adjusted serious adverse events (SAE): Patients randomized to the combination received more cycles of treatment. When cycles were adjusted for SAEs, plinabulin significantly decreased Grade 3/4 SAEs (p=0.0235) and Grade 4 SAEs (p<0.0001).
• The combination had manageable side effects: Plinabulin induced mostly asymptomatic transient hypertension, which mostly resolved within 4-6 hours after infusion without medication. In addition, plinabulin induced GI side effects, including nausea, vomiting, and diarrhea, which were effectively managed following a protocol adjustment to add the prophylactic use of antiemetics and increase time of infusion.

“NSCLC patients without targetable alterations whose disease has progressed on previous platinum-based therapy have a poor prognosis. Docetaxel is the current standard of care with >40% severe neutropenia and poor quality of life. In second or third-line NSCLC patients with EGFR wild-type, the phase 3 data suggest that adding plinabulin to docetaxel has a favorable benefit/risk ratio compared to docetaxel alone in significantly improving anti-cancer efficacy, and significantly reducing severe neutropenia and improving quality of life. This combination could be considered as a new option for second or third-line NSCLC patients without driver mutation, which is a severe unmet medical need,” said Dr. Feinstein, one of the lead principal investigators of Dublin-3 study at Piedmont Cancer Center, Atlanta.

ESMO Congress 2024 Presentation (1358P): Plinabulin/Docetaxel Versus Docetaxel in Survival Benefits of 2L/3L EGFR Wild-Type NSCLC after Platinum Regimens (DUBLIN-3): a Randomized Phase 3 Trial

• Presenter: Dr. Trevor M. Feinstein
• Poster Session: NSCLC, metastatic

Citation:
Han B., et al. Plinabulin plus docetaxel versus docetaxel in patients with non-small-cell lung cancer after disease progression on platinum-based regimen (DUBLIN-3): a phase 3, international, multicentre, single-blind, parallel group, randomised controlled trial. Lancet Respir Med. 2024 Sep 09: S2213-2600(24)00178-4.

About Plinabulin
Plinabulin is a novel first-in-class dendritic cell (DC) maturation therapeutic with durable anti-cancer benefit observed across multiple clinical studies. As a reversible binder at a distinct tubulin pocket, plinabulin does not change tubulin dynamics or antagonize tubulin stabilizing agents, such as docetaxel, which contributes to its differentiated activity and tolerability compared to other tubulin binders. Importantly, clinical data suggests that plinabulin enhances the cancer immunity cycle when used sequentially with chemotherapy/radiation and a checkpoint inhibitor. In addition, plinabulin significantly reduces chemotherapy induced neutropenia and could thereby increase docetaxel tolerability. Over 700 patients have been treated with plinabulin with good tolerability.

About Dublin-3 Study
Dublin-3 NSCLC was a global phase 3 randomized, controlled clinical trial comparing the combination of plinabulin and docetaxel to an active control arm of docetaxel alone (1:1 randomization) in second- and third-line NSCLC patients who had failed platinum doublet therapies, and who were epidermal growth factor receptor (EGFR) wild-type. Docetaxel was given on Day 1 in both arms at 75 mg/m² in each 21-day cycle. Plinabulin was given on Day 1, one hour after docetaxel, and on Day 8, both at 30 mg/m² in each cycle. The primary endpoint for the study was OS, and secondary endpoints were PFS, ORR, Duration of Response (DoR), Grade 4 neutropenia and Quality of Life.

About BeyondSpring
BeyondSpring is a global clinical-stage biopharmaceutical company 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, a potent inducer of dendritic cell maturation, in late-stage clinical development as a direct anti-cancer agent in NSCLC and a variety of cancer indications. BeyondSpring’s pipeline also includes three preclinical immuno-oncology assets. Additionally, BeyondSpring is an equity owner of SEED Therapeutics, Inc which is a pioneer in Target Protein Degradation technology and its application in innovative drug development. Learn more by visiting https://beyondspringpharma.com.

Investor Contact:
IR@beyondspringpharma.com

Media Contact:
PR@beyondspringpharma.com

FAQ

What were the main results of BeyondSpring's DUBLIN-3 Phase 3 study for NSCLC (BYSI)?

The DUBLIN-3 study showed that the plinabulin/docetaxel combination significantly improved overall survival, progression-free survival, and objective response rate compared to docetaxel alone in 2L/3L EGFR wild-type NSCLC patients. It also demonstrated >80% reduction in Grade 4 neutropenia and improved quality of life.

How did the plinabulin/docetaxel combination affect neutropenia rates in the DUBLIN-3 study (BYSI)?

The plinabulin/docetaxel combination showed >80% relative reduction in Grade 4 neutropenia compared to docetaxel alone. In Cycle 1 Day 8, the combination arm had 5.3% Grade 4 neutropenia vs 27.8% in the docetaxel arm, and across all cycles, it was 5.1% vs 33.6%, respectively.

What impact did the plinabulin/docetaxel combination have on quality of life in NSCLC patients (BYSI)?

The DUBLIN-3 study showed that the plinabulin/docetaxel combination improved quality of life based on Q-TWiST data. An exploratory analysis revealed a clinically meaningful relative gain of 18.5% (p=0.0393) in quality of life compared to the docetaxel arm.

What were the main side effects of the plinabulin/docetaxel combination in the DUBLIN-3 study (BYSI)?

The main side effects of the plinabulin/docetaxel combination included mostly asymptomatic transient hypertension and GI side effects such as nausea, vomiting, and diarrhea. These were manageable with prophylactic antiemetics and increased infusion time.