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BeyondSpring’s Lead Asset, Plinabulin, Prevents Docetaxel Chemo-Induced-Neutropenia (CIN) Due to a Mechanism of Action Differentiated from G-CSF
Evidence of Neutrophil Demargination and Bone Marrow Transit Time Reduction by Plinabulin Presented at Joint Meeting of the
Non-small cell lung cancer (NSCLC) patients received docetaxel chemotherapy plus Plinabulin (in doses up to 20 mg/m2) versus docetaxel alone in BeyondSpring’s Phase 2 Study 105. The beneficial effect of Plinabulin on docetaxel-induced CIN was measured at doses of 0 (n=14), 5 (n=14), 10 (n=13) or 20 (n=14) mg/m2 in NSCLC patients. A nonlinear mixed effects pharmacokinetic/pharmacodynamic (PK/PD) modeling approach was used to analyze absolute neutrophil count (ANC) to determine turnover rate (production and clearance) of ANC with Plinabulin (at different doses) and without Plinabulin.
The observed effects of Plinabulin on ANC demargination and bone marrow transit time reduction are consistent with IL-6 signaling in bone marrow and tissue microenvironment1, a unique mechanism of action and a potential complementary therapeutic effect in working with G-CSF.
“We previously presented data showing Plinabulin’s superior product profile, with more limited bone pain and protection against thrombocytopenia, for prevention of docetaxel CIN with its different mechanism of action from pegfilgrastim. We now show additional clinically relevant findings – increased ANC demargination and reduced ANC transit time consistent with Plinabulin’s IL-6 signaling – further differentiating Plinabulin’s MoA from pegfilgrastim,” said Dr.
“Plinabulin’s MoA in CIN is highly differentiated from G-CSF, which makes Plinabulin potentially complimentary to Neulasta for the prevention of CIN. Furthermore, there is a potential for increasing efficacy, while reducing safety concerns by combining these two classes of CIN agents. This provides a strong rationale for a development strategy in CIN that combines these two agents to create a treatment that is superior to each of them alone, both in terms of efficacy and safety/tolerability,” added Dr.
1 Suwa et al, Am J Physiol 2000;279:H2954-H2960
About Study 105
Plinabulin was given as a single dose per cycle 30 minutes after docetaxel chemotherapy, while Neulasta was given 24 hours after docetaxel chemotherapy, consistent with its approved product label. The Phase 2 portion met its primary endpoint, which was to determine the recommended Phase 3 Plinabulin dose, and the Phase 3 trial is ongoing.
About Chemotherapy-Induced Neutropenia (CIN)
The current standard of care for CIN prevention is G-CSF. However, G-CSF has limitations as described in its product information summary. Neutropenia, if severe enough, may cause doctors to lower target doses of chemotherapy, end therapy early and / or delay chemotherapy cycles, each of which has a negative effect on long-term outcomes of cancer care.
Cautionary Note Regarding Forward-Looking Statements