Trial in Progress:
Granulocyte colony stimulating factors (G-CSFs) (including Peg) reduce, but do not completely ameliorate CIN. Plinabulin is a novel, small molecule, single-dose-per cycle therapy, with equal activity against docetaxel CIN vs. Peg, but with several advantages: Plin has 1. Less bone pain, 2. Anticancer effects, and 3. Dosing 30 min after chemotherapy (chemo). The CIN nadir with Plin occurs in week 2 and with Peg in week 1 of the chemo cycle. All these features suggest a mechanism of action (MoA) with Plin that is different from Peg (Blayney, ASCO 2018; IASLC 2018). Neutrophil demargination with Plin and a reduced neutrophil transit time consistent with IL-6 signaling, and reversal of a LSK block in bone marrow, suggest protective rather than a stimulatory MoA for Plin in CIN (Blayney, SLB 2018; Ghosh, AACR 2018, Suwa, Am J Physiol 2000). Due to their differences in MoA, there is a strong rationale to combine Plin and Peg, as this offers the potential of better protection against CIN in both week 1 and 2 in the chemo cycle. In the Phase II portion of study BPI2358-106 (Study 106., NCT03294577), we evaluated the effects of the Plin combined with Peg on CIN and Bone Pain. Study 106 treated breast cancer (BC) patients with TAC with 6 mg Peg alone (Peg6), or Peg6+Plin. Plin dose was 20 mg/m2. Grade (Gr) 3 and 4 neutropenia frequency, duration of Gr 3 and 4 neutropenia (DSMN), and neutrophil nadir was based on absolute neutrophil counts, obtained on days 0, 1, 3, 6, 7, 8, 9, 10, 11, 12, 13, 15. Bone pain was assessed by a validated questionnaire on days 1, 2, 3, 4, 6, 7, 8, 9, and expressed as % of patients reporting bone pain.
Phase II Results.
The confirmatory phase 3 portion of study 106 will test addition of Plin to Peg6, which may offer superior protection against TAC CIN vs Peg alone without bone pain. The Plin/Peg combination is a novel CIN approach with the potential to optimize chemotherapy, by minimizing chemotherapy dose modifications due to CIN or bone pain.*p<0.05; **p<0.001; ***P<0.01 Peg+Plin vs Peg 6mg
Blayney:BeyondSpring Pharmaceuticals: Research Funding. Huang:BeyondSpring Pharmaceuticals: Employment. Mohanlal:BeyondSpring Pharmaceuticals: Employment.
