Plinabulin Combination Enhances Immune System and Prevents Neutropenia in Patients With Cancer

Plinabulin (NPI-2358) in combination with docetaxel, doxorubicin, cyclophosphamide (TAC), and pegfilgrastim (Neulasta) led to a dose-dependent increase in mean haptoglobin and absolute neutrophil count (ANC), demonstrating potency in the stimulation of the adaptive and innate immune system following previous positive efficacy and safety results, according to data analyzed from the phase III BPI-2358-106 study presented at the 2020 American Society of Clinical Oncology-Society for Immunotherapy of Cancer Clinical Immuno-Oncology Symposium.¹

“These data, coupled with our previous observation that plinabulin increases neutrophil counts, another member of the innate immune system, [mean] we now have multiple lines of clinical evidence to prove that plinabulin is a potent stimulator of the innate immune systems,” Ramon Mohanlal, MD, chief medical officer and executive vice president of Research and Development, at BeyondSpring, Inc., said in a statement to the press.²

The study cohort that included 42 patients with breast cancer showed a dose-dependent increase in ANC within 1 day of treatment with plinabulin, which was a significant improvement compared with the control of TAC plus pegfilgrastim (P<.001). Haptoglobin increase occurred within 3 days in the plinabulin group (P<.03). The increased ANC levels were consistent for approximately 1 week and the haptoglobin levels remained increased for more than 3 weeks.¹

In another study, anti—chemotherapy-induced neutropenia (CIN) efficacy benefit was observed with plinabulin versus pegfilgrastim in patients with breast cancer receiving TAC. Specifically, the median ANC profile was improved with plinabulin versus&shy; pegfilgrastim. Other benefits observed with plinabulin were reduced bone pain. The number of patients reporting at least 1 day of bone pain was 6% in the plinabulin/pegfilgrastim group versus 95% in the pegfilgrastim-alone group (P<.0001). For patients experiencing bone pain for at least 3 days, the rate was 38% in the group receiving pegfilgrastim versus 0% for the combination (P= .0056).¹

The development pipeline of plinabulin includes several trials, including the phase III DUBLIN-3 trial evaluating the efficacy of the agent plus docetaxel versus docetaxel/placebo in the second- or third-line treatment of patients with non—small cell lung cancer (NSCLC; NCT02504489), the phase II/III Protective-1 trial assessing duration of severe neutropenia with the agent versus pegfilgrastim in patients with solid tumors who are receiving docetaxel myelosuppressive chemotherapy (NCT03102606), the phase I/II NPI-2358-101 study looking at the efficacy of plinabulin in combination with docetaxel in patients with advanced NSCLC (NCT00630110), and the phase III BPI-2358-106 trial comparing duration of severe neutropenia in patients receiving TAC/pegfilgrastim with or without plinabulin (NCT03294577).

In NPI-2358-101 study of 38 patients with NSCLC, the median OS was 11.3 months in patients who received plinabulin plus docetaxel compared with 6.7 months in those who received docetaxel alone. The media PFS observed was 3.7 months in the combination group and 2.9 months in the monotherapy group. The overall response rate in patients who received plinabulin/docetaxel was 18% versus 10.5% in the docetaxel arm. The duration of response was 12.7 months versus 1 month, respectively (P<.05). The safety analysis showed that the addition of plinabulin prevented docetaxel-induced neutropenia and did not induce immune-related adverse events (P<.0002). The addition of plinabulin to docetaxel also prevented docetaxel dose-reduction toxicity.³

&ldquo;The dual ability to stimulate both the adaptive and innate immune system by plinabulin is valuable in its use in the prevention of CIN and treatment of cancer. This not only supports plinabulin&rsquo;s current phase III studies in NSCLC and in CIN, but also positions plinabulin as a preferred agent to be combined with IO [immune-oncology] therapies such as PD-1/PD-L1 inhibitors,&rdquo; Mohanlal said. &ldquo;Therefore, we have initiated a broad program combining plinabulin with checkpoint inhibitors with or without radiotherapy or chemotherapy, in collaboration with prominent academic centers.&rdquo;

Plinabulin is a differentiated immune and stem cell modulator and is in the late stages of its clinical development. In the presence of antigens, the small molecule inhibitor increases T-cell proliferation manner marrow.

References

1. Monhanlal RW and Huang L. Effect of plinabulin, a novel late-clinical stage immunotherapeutic agent on the adaptive and innate immune system. J Clin Oncol. 2020;38(suppl 5; abstr 8). doi: 10.1200/JCO.2020.38.5_suppl.8.
2. BeyondSpring's plinabulin stimulates both the adaptive and innate immune system in cancer patients [news release]. New York, New York: BeyondSpring, Inc; February 10, 2020. https://bit.ly/2Sqcy6o. Accessed February 13, 2020.
3. Mohanlal RW, Lloyd K, Huang L, Bazhenova L. Plinabulin as a novel small molecule clinical stage immune-oncology agent for NSCLC. J Clin Oncol. 2017;35(suppl 7S; abstr 139). doi: 10.1200/JCO.2017.35.7_suppl.139.