BeyondSpring (NASDAQ:BYSI) said the U.S. Food and Drug Administration has granted Fast Track designation to plinabulin in combination with docetaxel for patients with second- or third-line non-squamous non-small cell lung cancer (NSCLC) who have progressed after immune checkpoint inhibitor treatment and platinum-based chemotherapy and do not have actionable genomic alterations.
The company also disclosed a strategic transaction involving the sale of its interest in its Greater China subsidiary to Biolin Investment Limited. BeyondSpring said the arrangement is expected to provide it access to clinical data from approximately half of the 442 patients planned for its DUBLIN-4 Phase III trial, while allowing the company to retain global rights to plinabulin outside Greater China.
Fast Track designation and DUBLIN-4 plans
DUBLIN-4 is expected to enroll about 442 patients with post-immune checkpoint inhibitor, driver-negative, non-squamous NSCLC. Patients will be randomized in a double-blind, one-to-one design to receive either plinabulin plus docetaxel or docetaxel plus placebo. Overall survival will be the primary endpoint, while progression-free survival, objective response rate and safety measures will be secondary assessments.
BeyondSpring expects about half of planned enrollment to come from China and half from Western regions. The company’s disclosed timeline calls for study initiation around the end of 2026 or early 2027, with a pre-specified interim analysis expected in 2028. Qiu said the timing of that analysis will depend on enrollment and the accumulation of progression-free survival events.
Chairman and Co-Founder Lan Huang said the China transaction is intended to reduce the cost of generating data for the interim analysis, which is planned after 221 progression-free survival events. Huang said the company expects to receive data associated with approximately 50% of the study population through the arrangement.
Clinical rationale
Chief Scientific Officer June Lu said treatment options remain limited for patients whose cancer progresses after immune checkpoint inhibitors and platinum-based chemotherapy. Docetaxel remains an important treatment option in this setting, but Lu said historical median overall survival has been approximately nine to 11 months and severe neutropenia has exceeded 40%.
Lu noted that 12 Phase III studies, including PD-1 or PD-L1 inhibitor combinations and antibody-drug conjugate monotherapies, have not demonstrated an overall-survival improvement over docetaxel in similar patient populations.
BeyondSpring described plinabulin as a microtubule destabilizer intended to trigger release of GEF-H1, a signaling protein the company says can promote dendritic-cell maturation, antigen-presenting-cell activation and anti-tumor immune responses. The company also said plinabulin has shown neutropenia-mitigating activity and early evidence of effects on tumor vasculature.
In the company’s DUBLIN-3 Phase III study, involving 559 patients in second- and third-line EGFR wild-type NSCLC, plinabulin plus docetaxel produced a statistically significant overall-survival benefit with a hazard ratio of 0.82, according to Lu. In a 332-patient non-squamous subgroup, the reported overall-survival hazard ratio was 0.72, with a median survival extension of about 2.5 months.
Lu also cited a post hoc DUBLIN-3 analysis in patients previously treated with immune checkpoint inhibitors. In that subgroup, the company reported median overall survival of 15.8 months for plinabulin plus docetaxel, compared with 11.7 months for docetaxel alone. Median progression-free survival was reported at 5.6 months versus 3.8 months, while objective response rates were 18.2% and 8%, respectively.
Safety and regulatory considerations
BeyondSpring said more than 700 cancer patients have received plinabulin across its clinical programs. During the question-and-answer session, Lu said gastrointestinal side effects have been managed with medication, while hypertension observed with treatment has generally been transient and often resolved within four to six hours after infusion.
Huang said the DUBLIN-4 protocol, including its overall-survival primary endpoint, has been aligned with the FDA. Qiu added that the company plans to evaluate pharmacokinetics and efficacy across Asian and Western populations. He said the ultimate acceptability of the study data will depend on the trial’s results and the FDA’s review.
About BeyondSpring (NASDAQ:BYSI)
BeyondSpring Inc is a clinical-stage biopharmaceutical company focused on developing therapies for cancer and other serious diseases. The company’s lead product candidate is plinabulin, a selective immunomodulating microtubule-destabilizing agent designed to stimulate the immune system while affecting tumor-cell biology.
BeyondSpring has evaluated plinabulin for the prevention of chemotherapy-induced neutropenia, a potentially serious complication of cancer treatment, and for use in combination with other therapies in oncology, including treatment approaches for non-small cell lung cancer.
