BeyondSpring Unveils Final DUBLIN-3 Phase 3 Data at ESMO 2024

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. (“BeyondSpring”), a clinical-stage global biopharmaceutical company, presented final data on Dublin-3 study focusing on safety outcomes 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.

Docetaxel remains the standard of care for patients with non-small cell lung cancer (NSCLC) without targetable alterations despite severe neutropenia (>40%) that greatly impair patients’ quality of life. Multiple recent phase 3 studies in patients with EGFR wild-type NSCLC previously treated with immune checkpoint inhibitors have not shown overall survival (OS) benefit compared with docetaxel. However, two phase 3 studies, LUNAR and TROPION-Lung01, showed positive yet mixed outcomes compared with docetaxel.

The Dublin-3 study was a multicenter, single-blinded, randomized controlled trial conducted at 58 medical centers across Australia, China, and the USA. 559 patients with epidermal growth factor receptor (EGFR) wild-type NSCLC were randomly assigned 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.

The poster presentation highlighted the safety profile of the plinabulin/docetaxel combination versus docetaxel alone. The combination was well tolerated with similar percentages of patients experiencing at least one treatment emergent adverse event (TEAE); 99.6% in the combination arm and 99.3% in the docetaxel arm. There were fewer grade 4 TEAEs in the combination arm (19.0%) compared to 42.8% in the docetaxel arm.

Significantly, the combination demonstrated over 80% relative reduction in Grade 4 neutropenia. In the first cycle on Day 8, the combination arm had 5.3% Grade 4 neutropenia compared to 27.8% in the docetaxel alone arm. Across all cycles, the combination arm had 5.1% Grade 4 neutropenia versus 33.6% in the docetaxel alone arm. Hospital admissions due to febrile neutropenia were also lower in the combination arm (2.6% of patients) versus the docetaxel arm (5.0%).

The use of granulocyte-colony stimulating factor (G-CSF) was reduced in the combination arm in all cycles. Post-hoc analysis showed 56% of patients in the combination arm required G-CSF versus 66% in the docetaxel arm. The combination also improved quality of life (QoL) based on Q-TWiST data, with a clinically meaningful relative gain of 18.5% compared to the docetaxel arm.

Additionally, the combination showed a significant reduction in cycle-adjusted serious adverse events (SAE). When adjusted for treatment cycles, plinabulin significantly decreased Grade 3/4 SAEs and Grade 4 SAEs. The combination induced mostly asymptomatic transient hypertension and gastrointestinal (GI) side effects such as nausea, vomiting, and diarrhea, which were effectively managed with prophylactic use of antiemetics and longer infusion times.

Dr. Feinstein commented, "NSCLC patients whose disease has progressed on previous platinum-based therapy have a poor prognosis. Docetaxel is the current standard of care with high rates of severe neutropenia and poor quality of life. This phase 3 data suggests that adding plinabulin to docetaxel has a favorable benefit/risk ratio, significantly improving anti-cancer efficacy and reducing severe neutropenia while enhancing quality of life. This combination could be a new option for second or third-line NSCLC patients without driver mutation."

About Plinabulin
Plinabulin is a novel first-in-class dendritic cell maturation therapeutic with durable anti-cancer benefits observed across multiple clinical studies. It does not change tubulin dynamics or antagonize tubulin stabilizing agents, such as docetaxel. Clinical data suggests that plinabulin enhances the cancer immunity cycle when used sequentially with chemotherapy/radiation and a checkpoint inhibitor. Plinabulin also significantly reduces chemotherapy-induced neutropenia and increases 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 docetaxel alone in second- and third-line NSCLC patients who had failed platinum doublet therapies and who were EGFR wild-type. The primary endpoint was overall survival, and secondary endpoints included progression-free survival, objective response rate, duration of response, Grade 4 neutropenia, and quality of life.