The first patient with myelodysplastic syndrome has received iadademstat plus azacitidine in a phase 1 trial at the Medical College of Wisconsin.
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Trial Name: Iadademstat with Hypomethylating Agent in Patients with Myelodysplastic Syndrome
ClinicalTrials.gov Identifier: NCT06502145
Sponsor: Medical College of Wisconsin
Recruitment Contact: Medical College of Wisconsin Cancer Center Clinical Trials Office, 866-680-0505 ext 8900, cccto@mcw.edu
Completion Date: October 2027
The first patient with myelodysplastic syndrome (MDS) has been dosed with iadademstat (ORY-1001) in combination with azacitidine in a phase 1, investigator-initiated, dose-finding trial (NCT06502145).1
The study is evaluating iadademstat, a selective LSD1 inhibitor, and its safety and tolerability for the treatment of patients with MDS when given in combination with the standard-of-care azacitidine. The trial is being led at the Medical College of Wisconsin.
“MDS is a hematologic neoplasm with limited treatment options and poor prognosis. Our study is evaluating a novel combination regimen for the frontline management of patients with MDS using LSD1 inhibitor iadademstat, in combination with hypomethylating agents, given the encouraging results of this combination in AML. We are excited to start the study and offer this option to our patients with MDS in need of novel therapies,” Guru Subramanian Guru Murthy, MD, MS, at the Medical College of Wisconsin Cancer Center, in a press release.
In this phase 1, single-arm, open-label study, experts are evaluating the safety of iadademstat plus azacitidine for treating MDS. The trial plans to follow a 3+3 phase 1 dose-escalation design.2
Enrollment is open to patients aged 18 years or older with a diagnosis of MDS, or MDS/myeloproliferative neoplasm, chronic myelomonocytic leukemia as defined by the World Health Organization criteria. Patients are required to be intermediate-, high-, or very-high risk by the Revised International Prognostic Scoring System and have an ECOG performance status of 0, 1, or 2. Patients must also have a body weight of at least 50 kg and be able to swallow oral medications.
The primary end point of the study is to determine the recommended phase 2 dose of iadademstat.
Iadademstat previously demonstrated encouraging safety and clinical activity when given with azacitidine in a phase 2a trial in the first-line for patients with AML in the ALICE trial (EudraCT 2018-000482-36).1
The agent is currently being evaluated in combination with gilteritinib (Xospata) in the ongoing phase 1b FRIDA trial (NCT05546580) for the potential treatment of patients with relapsed/refractory AML with FLT3 mutations, as well as in combination with azacitidine and venetoclax (Venclexta) in the first-line setting for patients with AML in an investigator-initiated study led by Oregon Health & Science University. This combination is also being evaluated in a trial sponsored by the U.S. National Cancer Institute to further the clinical development of iadademstat in different types of hematologic and solid cancers.
Beyond hematologic malignancies, LSD1 inhibition has emerged as a potential therapeutic approach in select solid tumors, including small cell lung cancer (SCLC), neuroendocrine tumors (NET), medulloblastoma, and others. In the phase 2a CLEPSIDRA trial, this approach is under investigation in combination with platinum/etoposide as a second-line treatment for patients with extensive-disease SCLC.
A collaborative phase 2 trial with is also evaluating the agent in combination with paclitaxel in relapsed/refractory neuroendocrine carcinomas at Fox Chase Cancer Center, and a phase 1/2 randomized trial is evaluating the treatment in the first-line setting for patients with extensive disease SCLC when given combination with ICI sponsored by NCI and led by the Memorial Sloan Kettering Cancer Center (IND approved). Additional investigator-initiated studies are ongoing.
Further, the FDA previously granted iadademstat an orphan drug designation for SCLC in the US, as well as an orphan drug designation for AML treatment in the European Union.
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