BeyondSpring Pharmaceuticals will bring its lead compound, Plinabulin, to phase 3 clinical trials for the treatment of non-small cell lung cancer (NSCLC) in the first quarter of 2015. The news follows the 2014 ASCO Annual Meeting in the beginning of June, where Rebecca Heist, MD, presented a poster of data concerning Plinabulin with docetaxel treatment of advanced NSCLC in phase 2 trials.
“The data from our phase 2 study validated Plinabulin’s unique mechanism of action and allowed us to tailor our next trial using a unique biomarker-driven approach to patients who will be most likely to benefit from treatment with Plinabulin, such as those with large lung cancer lesions, and thus more dependent on the abundant tumor vasculature,” said Dr. Lan Huang, PhD, chief executive officer of BeyondSpring, in a news release from the company.
Details of the phase 3 trial are not yet available, but Dr. Gloria Lee, MD, PHD, chief medical officer of BeyondSpring, stated, “Based on these data [from phase 2], we are able to utilize our unique mechanism-based approach to tailor the design of the phase 3 trial to include patients with large tumors.” She noted that approximately 500 NSCLC patients at 35 sites between the United States and China will enroll in the trial beginning in the first quarter of 2015. Only 25% of patients will be American, and 75% will be Chinese. “Leveraging our unique, cross-border development model, we expect to substantially enhance the efficiency of resource utilization with respect to both the enrollment time and cost for this pivotal study,” said Dr. Lee.
As described by Dr. Heist’s abstract in the phase 2 trial, 163 NSCLC patients were randomized into one of three groups (docetaxel, or docetaxel with one of two doses of Plinabulin) and treated. “Our phase 2 study demonstrated a longer median overall survival for this particular subset of patients–11.5 months for combination Plinabulin plus docetaxel compared to just 7.8 months for patients receiving docetaxel alone,” said Dr. Huang. “This is a substantial improvement compared to approved lung cancer drugs which, in pivotal trials, demonstrated overall survival of approximately 8 months.”
As a secondary point of interest, the clinical research team conducted a post hoc exploratory analysis and discovered that patients with large (greater than 3 cm) lung tumors had a greater overall survival than other patients. This is a key driving factor of the phase 3 trial, as enrollment will be enriched with patients most likely to benefit from treatment. It is possible these patients were most well-served due to the mechanism of Plinabulin in targeting tumor vasculature and inducing apoptosis via the JNK signaling pathway.
Furthermore, patients tolerated Plinabulin with mild to moderate adverse events including nausea, fatigue, diarrhea, constipation, and loss of appetite. Some Grade 3 and Grade 4 adverse events occurred with Plinabulin and docetaxel combined, but events were lower in this group than in the docetaxel alone group. The phase 3 trial will continue to investigate the safety profile of Plinabulin and further investigate efficacy in treating NSCLC.