BeyondSpring Announces Positive Follow-Up Results for Phase 2 Trial of Plinabulin in Advanced NSCLC at WCLC 2015

NEW YORK, Sept. 15, 2015 (GLOBE NEWSWIRE) — BeyondSpring Pharmaceuticals, Inc., a clinical stage biopharmaceutical company focused on the development of innovative cancer therapies, today announced that data supporting the ongoing development of its lead compound, Plinabulin, were presented in two posters at the 16th World Conference on Lung Cancer (WCLC), which is hosted by the International Association for the Study of Lung Cancer (IASLC), and took place September 6-9, 2015 in Denver, CO.

Dr. Lan Huang, Co-founder and CEO of BeyondSpring Pharmaceuticals, commented, “Data from our mechanism-based analysis from the Phase 2 study show that treatment with Plinabulin combined with docetaxel in patients with advanced non-small cell lung cancer, who have lung lesions greater than 3 centimeters, potentially could offer substantial improvement in overall survival. These results clearly validate the design of our ongoing Phase 3 study, which mirrors the patient population identified through the mechanism-based subset analysis, with adequate sample size permitting robust statistical analysis for survival benefit. Furthermore, we provided an update on the complete study design of the Phase 3 trial at WCLC. We are excited to have presented observations supporting our ongoing trial and new directions to expand the development program of our lead asset Plinabulin at one of the world’s premier lung cancer conferences and look forward to continuing its evaluation as a possible treatment option for patients with advanced NSCLC.”

Data results from the two studies presented are as follows:

Abstract #1505 / P3.01-057: Randomized Phase 2 Study of Plinabulin Combined with Docetaxel in Patients with Advanced Non-Small Cell Lung Cancer – Mechanism-Based Efficacy Analyses

First / Presenting Author: Lyudmila Bazhenova, MD
Poster Session: Treatment of Advanced Diseases – NSCLC
Date, Time: Wed, September 9; 9:30 a.m. – 4:30 p.m. MT
Location: Exhibit Hall (Hall B+C)

Data from 105 patients in a mechanism-based efficacy analysis from a Phase 2 randomized study suggest the clinical benefit of Plinabulin combined with docetaxel, a standard chemotherapy, improves overall survival (OS) in patients with advanced NSCLC who have lung lesions greater than 3 centimeters (cm). The full results from the intent-to-treat (ITT) analysis were previously reported at the 2014 American Society of Clinical Oncology (ASCO) Annual Meeting.

Patients in the sub-analysis were randomized one-to-one in a Plinabulin plus docetaxel treatment arm compared to docetaxel alone. Patients in the treatment arm received 30 mg/m2 dose of Plinabulin, which was selected as the dose for an ongoing Phase 3 study.

Analysis of median OS according to tumor size of any lesion demonstrated evident OS benefit in favor of Plinabulin and docetaxel treatment arm, as shown by hazard ratio (HR). In patients with lesions greater than 3 cm, HR gradually decreased to <0.6. The HR range was 0.97-0.50. This trend was consistently observed independent of number of prior treatments. The importance of location of lesions was also analyzed. It was apparent that patients with advanced lesions in lung parenchyma received more benefit from Plinabulin plus docetaxel treatment (HR=0.76) regardless of lesion size. The HR range (0.84-0.44) based on lung lesion size was also consistent with findings based on size of all lesion including extra-pulmonary lesions.

Treatment with Plinabulin plus docetaxel was well tolerated; with most common adverse events consistent with chemotherapy side effects and including nausea, fatigue, diarrhea, constipation, anorexia, fever, vomiting, transient blood pressure elevation, which were mostly Grade 1-2.

Importantly, treatment with Plinabulin plus docetaxel reduced neutropenia (low white blood cell count) associated with treatment with docetaxel alone: across all grades neutropenia was reduced from 36% to 8%; and in Grades 3/4 neutropenia was reduced from 29% to 8% (both statistically significant). In addition, use of granulocyte-colony stimulating factor (G-CSF) was also substantially reduced from 29% to 14% in the treatment arm. The mechanism-based analysis identified lesion size and anatomy to be important factors in overall survival improvement. Patients with lung lesion greater than 3 cm, regardless of the extent of prior chemotherapy, appeared to have benefit from Plinabulin combined with docetaxel.

Based on this finding, BeyondSpring has initiated an ongoing, global pivotal Phase 3 trial in advanced NSCLC patients who have pulmonary lesions greater than 3 cm (Poster #1498).

Abstract #1498 / P2.01-101: Randomized Phase 3 Assessment of Second-Line Treatment with Docetaxel + Plinabulin Compared to Docetaxel Alone in Patients with Advanced Non-Small Cell Lung Cancer with at Least 1 Large Lung Lesion

First / Presenting Author: Lyudmila Bazhenova, MD
Poster Session: Treatment of Advanced Diseases – NSCLC
Date, Time: Tue, September 8; 9:30 a.m. – 4:30 p.m. MT
Location: Exhibit Hall (Hall B+C)

The global, pivotal Phase 3 trial of Plinabulin as a second-line treatment is being conducted in patients with advanced, metastatic NSCLC who have at least one large lung lesion, greater than 3 cm, EGFR wild type and ALK wild type tumors, and who have previously failed one line of chemotherapy, which enables patients who failed checkpoint inhibitor treatment to have the opportunity to be enrolled in this Phase 3 study. Specifically, the multi-center, randomized, open label study is evaluating treatment with Plinabulin combined with docetaxel compared to docetaxel alone. The primary endpoint is median duration of OS, with secondary endpoints including median duration of progression-free survival (PFS), objective response rate (ORR) and duration of response (DOR), safety, severity of neutropenia and G-CSF use, as well as population pharmacokinetics (PK) in patients enrolled in the U.S. and China. Planned number of patients for this study is a total 550 patients, with approximately 110 from the U.S. and 440 from China. Patients will be stratified on the basis of ECOG performance status and region.

UCSD is the first site initiated in the U.S. for this global Phase 3 trial, for which Dr. Bazhenova will lead as the Principal Investigator. As the U.S. Principal Investigator, Dr. Bazhenova commented, “We are excited about this Phase 3 trial because of the statistically significant extended duration of response seen in the Phase 2 trial in the combination arm compared to the docetaxel arm, 12.7 months versus 1.5 months, which is consistent with Plinabulin’s immuno-oncology mechanism. In addition, several unique advantages speak for Plinabulin, as it significantly reduces docetaxel induced neutropenia.”   

An interim analysis is planned at time of 50% of death events. Final outcome analysis is planned after 434 death events which will provide a 0.85 power to detect a statistically significant treatment effect.

Plinabulin works via multiple mechanisms of action to target the tumor microenvironment, including obliterating existing tumor vasculature and anti-angiogenesis, inducing tumor cell apoptosis via activation of JNK pathway, and generating amplified immune system response to fight cancer through induction of dendritic cell maturation.

About BeyondSpring Pharmaceuticals

BeyondSpring Pharmaceuticals is a clinical stage biopharmaceutical company focused on the development of innovative cancer therapies. BeyondSpring is focused on the advancement and commercialization of Plinabulin, a novel, Phase 3-ready cancer therapeutic initially targeting non-small-cell lung cancer (NSCLC). Led by an expert management team consisting of pharmaceutical industry veterans from the U.S. and China, the Company is well positioned to further advance lead product candidate, Plinabulin. For more information, visit www.beyondspringpharma.com.

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