- Plinabulin was well tolerated and only one out of the 10 patients enrolled had non-engraftment related neutropenic fevers or febrile neutropenia (FN) with the plinabulin/pegfilgrastim combination
NEW YORK, August 29, 2022 – BeyondSpring Inc. (the “Company” or “BeyondSpring”) (NASDAQ: BYSI), a clinical stage global biopharmaceutical company focused on developing innovative cancer therapies to improve clinical outcomes for patients who have a high unmet medical need, today announced data from a poster presentation at the 19th International Myeloma Society Annual Meeting being held August 25-27, 2022, in Los Angeles, California. This is an open label, investigator-initiated study (NCT05130827) conducted at Memorial Sloan Kettering Cancer Center (MSK) that is evaluating the reduction in neutropenia burden with lead asset plinabulin in combination with pegfilgrastim in multiple myeloma (MM) patients who have undergone autologous hematopoietic stem cell transplantation (AHCT) and have received a high dose of melphalan, a type of chemotherapy. To date, plinabulin appears well tolerated, and preliminary data show that only one out of the 10 patients enrolled (10%) had non-engraftment related neutropenic fevers or febrile neutropenia (FN) with plinabulin and pegfilgrastim, compared to a historical number of 60% of FN with standard of care. Enrollment is ongoing, and full trial results will be presented at a later date.
“The use of high dose melphalan with AHCT is a well-established therapeutic strategy for MM. However, it’s associated with a high frequency of FN, typically around 60% of patients, despite prophylactic use of pegfilgrastim and antibiotics. This can lead to significant clinical complications resulting in extended hospitalization, readmissions and increased financial cost,” said Dr. Gunjan Shah, hematologist oncologist and principal investigator of the study at MSK. “With symptom burden during AHCT peaking at the time of white blood cell nadir (lowest point), it’s important to identify strategies that can help reduce the burden of neutropenia. The preliminary observation from this pilot trial is that adding plinabulin to prophylactic pegfilgrastim and antibiotics helped to prevent the occurrence of non-engraftment-related FN, which has the potential to be clinically meaningful and also beneficial from a health economics perspective.”
In this pilot study, patients with MM are treated with a single dose of melphalan and undergo AHCT. Patients receive a plinabulin 40 mg fixed dose IV infusion, and on day +1, pegfilgrastim 6 mg is administered per standard of care. The objectives of this study were to evaluate neutropenia burden, safety, tolerability, neutrophil and platelet engraftment rate, disease response, progression free survival, overall survival and patient reported outcome (PRO) assessment of symptom burden.
Poster Presentation Details
Title: Plinabulin after Autologous Hematopoietic Cell Transplant to Decrease Duration of Neutropenia and Improve Quality of Life Peri-Transplant
Abstract #: P-194
Presenter: Dr. Gunjan Shah, hematologist oncologist and principal investigator of the study at MSK
- 10/15 patients have been enrolled and received plinabulin on Day 0 with a median age of 64 (range 58-74) and 40% of them were female. Patients received melphalan 140 mg/m2 (n=3) or 200 mg/m2 (n=7);
- Efficacy summary:
- Median white blood count (WBC) on Day 0, 1 and 2 was 7.6 (3.6 – 9.8), 5 (3.2 – 13.6) and 18.7 (5.1-59.1) x 10^9 cells/L, respectively;
- Of the eight patients who have engrafted to date, median time to absolute neutrophil count (ANC) > 0.5 x 10^9 cells/L was 11 days (range 10-16). The median number of days of ANC <0.1 and <0.5 were two (range 1-3) and five days (range 4-9), respectively;
- Six patients had fever at median of eight days post AHCT (range 9-12). Five patients with engraftment syndrome were treated with steroids, and there was one patient with non-engraftment-related neutropenic fever (representing 10% of the patients enrolled);
- Safety Summary:
- No patients have progressed or died;
- Half of the patients had hypertension immediately after the plinabulin infusion, which is a known toxicity and resolved within a few hours;
- PROMIS-29 PRO data were collected and will be analyzed.
Dr. Ramon Mohanlal, BeyondSpring’s executive vice president of R&D and chief medical officer, added, “Plinabulin has a fast onset mechanism of action that is different and complementary to that of G-CSF. We continue to evaluate new opportunities with plinabulin to unlock its tremendous potential. Preclinical data have shown that plinabulin induces apoptotic cell death in multiple cell lines and cells from MM patients. Therefore, the AHCT setting in MM is of particular interest because plinabulin has the potential to exert both neutropenia prevention and an anti-cancer benefit.”
Plinabulin, BeyondSpring’s lead asset, is a selective immunomodulating microtubule-binding agent, which is a potent antigen presenting cell (APC) inducer that is being developed as an anticancer agent. Plinabulin triggers the release of the immune defense protein, GEF-H1, which leads to two distinct effects: first is a durable anticancer benefit due to the maturation of dendritic cells resulting in the activation of tumor antigen-specific T-cells to target cancer cells and the second is a CIN prevention benefit. Plinabulin has single agent anti-cancer activity in a number of cancers including small cell lung cancer (SCLC) and multiple myeloma (MM). Plinabulin also exerts early-onset of action in the prevention of chemotherapy-induced neutropenia (CIN) by boosting the number of hematopoietic stem/progenitor cells (HSPCs).
Headquartered in New York City, BeyondSpring is a clinical stage global biopharmaceutical company focused on developing innovative cancer therapies to improve clinical outcomes for patients who have high unmet medical needs. BeyondSpring’s first-in-class lead asset, plinabulin, is being developed as a potential “pipeline in a drug” in various cancer indications as a direct anti-cancer agent and to prevent chemotherapy-induced neutropenia (CIN). The plinabulin and G-CSF combination for the prevention of CIN has demonstrated positive Phase 3 data in the PROTECTIVE-2 study. In the DUBLIN-3 study, a global, randomized, active controlled Phase 3 study, the plinabulin and docetaxel combination met the primary endpoint of extending overall survival compared to docetaxel alone in 2nd/3rd line non-small cell lung cancer (NSCLC) (EGFR wild type). Additionally, plinabulin is being broadly studied in combination with various immuno-oncology regimens that could boost the efficacy of PD-1/PD-L1 antibodies in seven different cancers. Lastly, BeyondSpring’s pipeline includes three preclinical immuno-oncology assets and a subsidiary, SEED Therapeutics, which is leveraging a proprietary targeted protein degradation drug discovery platform.
Cautionary Note Regarding Forward-Looking Statements
This press release includes forward-looking statements that are not historical facts. Words such as “will,” “expect,” “anticipate,” “plan,” “believe,” “design,” “may,” “future,” “estimate,” “predict,” “objective,” “goal,” or variations thereof and variations of such words and similar expressions are intended to identify such forward-looking statements. Forward-looking statements are based on BeyondSpring’s current knowledge and its present beliefs and expectations regarding possible future events and are subject to risks, uncertainties and assumptions. Actual results and the timing of events could differ materially from those anticipated in these forward-looking statements as a result of several factors including, but not limited to, difficulties raising the anticipated amount needed to finance the Company’s future operations on terms acceptable to the Company, if at all, unexpected results of clinical trials, delays or denial in regulatory approval process, results that do not meet the Company’s expectations regarding the potential safety, the ultimate efficacy or clinical utility of our product candidates, increased competition in the market, and other risks described in BeyondSpring’s most recent Form 20-F on file with the U.S. Securities and Exchange Commission. All forward-looking statements made herein speak only as of the date of this release and BeyondSpring undertakes no obligation to update publicly such forward-looking statements to reflect subsequent events or circumstances, except as otherwise required by law.
Ashley R. Robinson
LifeSci Advisors, LLC
Darren Opland, Ph.D.