BeyondSpring Presents Final Data Analysis of DUBLIN-3 Phase 3 Study in 2L/3L EGFR Wild-type NSCLC at ESMO Congress 2024
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.
BeyondSpring (NASDAQ: BYSI) ha presentato dati finali sullo studio di fase 3 DUBLIN-3 al Congresso ESMO 2024, mostrando significativi miglioramenti nella sopravvivenza globale, sopravvivenza libera da progressione e tasso di risposta obiettivo per la combinazione plinabulin/docetaxel nei pazienti con NSCLC di tipo wild-type EGFR in seconda e terza linea. La combinazione ha dimostrato un rapporto favorevole tra benefici e rischi rispetto al docetaxel da solo, inclusi:
1. >80% di riduzione relativa nella neutropenia di grado 4
2. Ridotto utilizzo di G-CSF
3. Migliore qualità della vita
4. Significativa riduzione degli eventi avversi gravi aggiustati per ciclo
Lo studio suggerisce che questa combinazione potrebbe rappresentare una nuova opzione per i pazienti NSCLC in seconda o terza linea senza mutazione driver, rispondendo a un bisogno medico insoddisfatto.
BeyondSpring (NASDAQ: BYSI) presentó datos finales del estudio de fase 3 DUBLIN-3 en el Congreso ESMO 2024, mostrando mejoras significativas en supervivencia global, supervivencia libre de progresión y tasa de respuesta objetiva para la combinación de plinabulin/docetaxel en pacientes con NSCLC de tipo salvaje EGFR en segunda y tercera línea. La combinación demostró un razón favorable entre beneficio y riesgo en comparación con el docetaxel solo, que incluye:
1. >80% de reducción relativa en neutropenia de grado 4
2. Uso reducido de G-CSF
3. Mejor calidad de vida
4. Reducción significativa en eventos adversos graves ajustados por ciclo
El estudio sugiere que esta combinación podría ser una nueva opción para pacientes de NSCLC en segunda o tercera línea sin mutación driver, abordando una necesidad médica insatisfecha.
BeyondSpring (NASDAQ: BYSI)는 ESMO Congress 2024에서 DUBLIN-3 3상 연구의 최종 데이터를 발표하며, 2L/3L EGFR 와일드타입 NSCLC 환자에게서 plinabulin/docetaxel 조합의 전체 생존율, 무진행 생존율 및 객관적인 반응률에서 유의미한 개선을 보여주었습니다. 이 조합은 독타제졸 단독보다 유리한 이익/위험 비율을 나타냈으며, 포함된 내용은 다음과 같습니다:
1. 80% 이상의 상대적 감소가 있는 4등급 호중구감소증
2. G-CSF 사용 감소
3. 향상된 삶의 질
4. 사이클 조정 심각한 이상반응의 유의미한 감소
본 연구는 이 조합이 드라이버 변이가 없는 2차 또는 3차 NSCLC 환자를 위한 새로운 옵션이 될 수 있다고 제안하며, 충족되지 않은 의료 필요를 해결하고 있습니다.
BeyondSpring (NASDAQ: BYSI) a présenté des données finales sur l'étude de phase 3 DUBLIN-3 lors du congrès ESMO 2024, montrant des améliorations significatives dans la surbavie globale, la survie sans progression et le taux de réponse objective pour la combinaison de plinabulin/docetaxel chez les patients NSCLC de type sauvage EGFR en 2L/3L. La combinaison a démontré un rapport bénéfice/risque favorable par rapport au docétaxel seul, comprenant :
1. >80% de réduction relative de la neutropénie de grade 4
2. Utilisation réduite de G-CSF
3. Amélioration de la qualité de vie
4. Réduction significative des événements indésirables graves ajustés par cycle
L'étude suggère que cette combinaison pourrait être une nouvelle option pour les patients NSCLC en deuxième ou troisième ligne sans mutation driver, répondant ainsi à un besoin médical non satisfait.
BeyondSpring (NASDAQ: BYSI) hat beim ESMO Kongress 2024 endgültige Daten zur DUBLIN-3 Phase-3-Studie vorgestellt. Diese zeigen bedeutende Verbesserungen in der gesamtüberlebensrate, progressionsfreien Überlebensrate und objektiven Ansprechrate für die Kombination von Plinabulin und Docetaxel bei Patienten mit NSCLC vom EGFR-Wildtyp in der 2L/3L-Phase. Die Kombination wies ein günstiges Verhältnis von Nutzen zu Risiken im Vergleich zu Docetaxel allein auf, einschließlich:
1. >80% relative Reduktion der Neutropenie Grad 4
2. Reduzierten Einsatz von G-CSF
3. Verbesserte Lebensqualität
4. Signifikante Reduktion der schwerwiegenden unerwünschten Ereignisse pro Zyklus
Die Studie legt nahe, dass diese Kombination eine neue Option für NSCLC-Patienten in der zweiten oder dritten Linie ohne Treibermutation darstellen könnte und somit ein unbefriedigtes medizinisches Bedürfnis anspricht.
- 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)
- Plinabulin induced mostly asymptomatic transient hypertension
- Plinabulin induced GI side effects, including nausea, vomiting, and diarrhea
Insights
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
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.
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.
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 (>
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 (>
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 and99.3% 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 to27.8% in docetaxel alone (81% reduction, p<0.0001). The combination arm had a 5.1 % Grade 4 neutropenia in all cycles Day 8 compared to33.6% 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 >
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
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