On October 1, 2019 Stemline Therapeutics, Inc. (Nasdaq: STML), a commercial-stage biopharmaceutical company focused on the development and commercialization of novel oncology therapeutics, reported updated clinical data on the felezonexor (SL-801) Phase 1 trial in patients with advanced solid tumors at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) 2019 Annual Congress in Barcelona, Spain (Press release, Stemline Therapeutics, OCT 1, 2019, View Source [SID1234539973]). The presentation is now available on the Stemline website, www.stemline.com, under the Scientific Presentations tab.
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Felezonexor is a novel, oral, small molecule that reversibly inhibits Exportin-1 (XPO1), a nuclear export protein, overexpressed in a variety of solid and hematologic malignancies. XPO1 is a mediator of nuclear-cytoplasmic transport of nuclear proteins and has been associated with aggressive tumor behavior and poor prognosis. XPO1 is a clinically validated target in oncology, and the FDA recently approved an XPO1 inhibitor drug, in combination with other agents, for the treatment of certain oncology patients (with relapsed/refractory multiple myeloma). Felezonexor has demonstrated potent in vitro and in vivo preclinical activity. Interim results from the ongoing Phase 1 clinical trial reported at ESMO (Free ESMO Whitepaper) are summarized below.
Key Felezonexor Highlights from Ongoing Phase 1 Trial in Patients with Advanced Solid Tumors
Partial response (PR) achieved with single agent felezonexor in a 4th line patient with KRAS-positive, microsatellite stable (MSS) colorectal cancer (18+ weeks, ongoing)
– PR (RECIST 1.1 criteria) reported after 2 cycles of felezonexor (70mg then 65mg due to elevated creatinine), with the patient demonstrating serial reductions in the two target lesions (liver and spleen)
– Treatment with felezonexor ongoing (cycle 6); Next staging pending
Stable disease (SD) achieved in 12 patients, with 11/12 of these patients 3rd line or greater
Five patients had SD for 4 and 11 months, including 1 patient with basal cell carcinoma with SD for ~11 months
– 20% disease shrinkage noted in one patient with heavily pre-treated neuroendocrine tumor
Pharmacokinetic (PK) analyses suggest dose-dependent increases in exposure
Dosing regimen previously adjusted (Schedule B) to improve tolerability while maintaining dose intensity; 1 patient in Schedule B (n=7) experienced grade 3 weakness, the 75mg cohort has been expanded and enrollment continues
Ideal therapeutic dose and regimen not yet determined, and dose escalation ongoing
Further updates expected as Phase 1 trial continues to enroll
Ivan Bergstein, M.D., CEO of Stemline, commented, "We are very encouraged to witness evidence of clinical activity in a patient with a heavily pretreated and highly mutated solid tumor with poor prognostic features with single agent felezonexor in a regimen and dose that has potentially not yet been fully optimized. We continue to enroll patients with the goal of refining the ideal dose and schedule to take forward into a focused and abbreviated Phase 2 program, and plan to provide periodic updates as the Phase 1 progresses."
About ELZONRIS
ELZONRIS (tagraxofusp-erzs), a CD123-directed cytotoxin, is approved by the U.S. Food and Drug Administration (FDA) and commercially available in the U.S. for the treatment of adult and pediatric patients, two years or older, with blastic plasmacytoid dendritic cell neoplasm (BPDCN). For full prescribing information in the U.S., visit www.ELZONRIS.com. In Europe, a marketing authorization application (MAA) is under review by the European Medicines Agency (EMA). ELZONRIS is also being evaluated in additional clinical trials in other indications including chronic myelomonocytic leukemia (CMML), myelofibrosis (MF), and acute myeloid leukemia (AML).
About BPDCN
BPDCN is an aggressive hematologic malignancy with historically poor outcomes and an area of unmet medical need. BPDCN typically presents in the bone marrow and/or skin and may also involve lymph nodes and viscera. The BPDCN cell of origin is the plasmacytoid dendritic cell (pDC) precursor. The diagnosis of BPDCN is based on the immunophenotypic diagnostic triad of CD123, CD4, and CD56, as well as other markers. For more information, please visit the BPDCN disease awareness website at www.bpdcninfo.com.
About CD123
CD123 is a cell surface target expressed on a wide range of myeloid tumors including blastic plasmacytoid dendritic cell neoplasm (BPDCN), certain myeloproliferative neoplasms (MPNs) including chronic myelomonocytic leukemia (CMML) and myelofibrosis (MF), acute myeloid leukemia (AML) (and potentially enriched in certain AML subsets), myelodysplastic syndrome (MDS), and chronic myeloid leukemia (CML). CD123 has also been reported on certain lymphoid malignancies including multiple myeloma (MM), acute lymphoid leukemia (ALL), hairy cell leukemia (HCL), Hodgkin’s lymphoma (HL), and certain Non-Hodgkin’s lymphomas (NHL). In addition, CD123 has been detected on some solid tumors as well as autoimmune disorders including cutaneous lupus and scleroderma.