A randomized, open-label study of the efficacy and safety of galinpepimut-S (GPS) maintenance monotherapy compared to investigator's choice of best available therapy (BAT) in patients with acute myeloid leukemia (AML) who have achieved complete remission (CR) after second-line salvage therapy.

person Omer Hassan Jamy University of Alabama at Birmingham, Birmingham, AL info_outline Omer Hassan Jamy, Sharif S. Khan, Panagiotis Tsirigotis, Benjamin Kent Tomlinson, Mathilde Hunault-Berger, Uwe Platzbecker, Ioanna Sakellari, Ana Vidovic, Pau Montesinos, Teresa Bernal del Castillo, Daniel Egan, Hana Safah, Gary J. Schiller, Mathias Haenel, Agata Obara, Tsung-Chih Chen, Marcello Rotta, Stavroula Giannouli, Aleksandar Savic, Dragan Cicic

Authors person Omer Hassan Jamy University of Alabama at Birmingham, Birmingham, AL info_outline Omer Hassan Jamy, Sharif S. Khan, Panagiotis Tsirigotis, Benjamin Kent Tomlinson, Mathilde Hunault-Berger, Uwe Platzbecker, Ioanna Sakellari, Ana Vidovic, Pau Montesinos, Teresa Bernal del Castillo, Daniel Egan, Hana Safah, Gary J. Schiller, Mathias Haenel, Agata Obara, Tsung-Chih Chen, Marcello Rotta, Stavroula Giannouli, Aleksandar Savic, Dragan Cicic Organizations University of Alabama at Birmingham, Birmingham, AL, Bon Secours St Francis Health System, Greenville, SC, University General Hospital Attikon, Chaidari, Greece, University Hospitals Seidman Cancer Center, Cleveland, OH, CHU Angers, Angers, France, University Hospital Leipzig, Leipzig, Germany, General Hospital of Thessaloniki “G. Papanikolaou, Pilea Chortiatis, Greece, University Clinical Center of Serbia, Belgrade, Serbia, Hospital Universitario y Politecnico La Fe, Valencia, Spain, Hospital Universitario Central de Asturias, Asturias, Spain, University of Washington Medical Center, Seattle, WA, Tulane Cancer Center, New Orleans, LA, Department of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA, Klinikum Chemnitz gGmbH, Chemnitz, Germany, Swietokrzyskie Centrum Onkologii, Kielce, Poland, Taichung Veterans General Hospital, Taichung City, Taiwan, Colorado Blood Cancer Institute, Denver, CO, Hippokration General Hospital, Athina, Greece, Clinical Centre of Vojvodina, Novi Sad, Serbia, SELLAS Life Sciences Group, Inc., New York, NY Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Sellas Life Sciences Group Background: Patients with relapse/refractory (r/r) AML have poor outcomes. Allogeneic stem cell transplantation (allo-SCT) can potentially cure some patients with r/r AML who achieve second CR (CR2). However, barriers to transplantation such as advanced age, poor functional status/comorbidities or lack of donor exist and not all patients are able to proceed to allo-SCT. Therefore, novel strategies to decrease relapse risk in these patients are urgently needed. A National Cancer Institute consensus study on prioritization of cancer antigens ranked the Wilms tumor 1 (WT1) protein as the top immunotherapy target in cancer. WT1 has emerged as an encouraging vaccine target in AML due to its overexpression in leukemic blasts. Maintenance therapy with Galinpepimut-S (GPS), a multivalent heteroclitic WT1 peptide vaccine, has shown promising activity in patients with AML by inducing a strong innate immune response (CD4+/CD8+) against the WT1 antigen and across a broad range of HLA types. Methods: This is an open-label, multicenter, randomized, phase III study of GPS vs. BAT in patients with AML in CR2/CRp2 (CR2 with incomplete platelet recovery). BAT may include observation, low dose cytarabine and hypomethylating agents +/- venetoclax. The primary endpoint of the study is overall survival (OS). Secondary endpoints include safety and tolerability of GPS and leukemia-free survival. Exploratory endpoints include WT1-specific immune response dynamics in blood and bone marrow. Approximately 125 - 140 patients will enroll, in a 1:1 ratio, to provide at least 90% power under an assumed hazard ratio of 0.52, based on median OS of 8.0 m (BAT) and 15.4m (GPS). Randomization will be stratified by duration of CR1 ( < 12m vs. ≥12m), Cytogenetics (poor-risk vs. all other), CR2 vs. CRp2 and measurable residual disease (MRD) after CR2 (MRD- vs. MRD+). Inclusion criteria consists of willing subjects ≥18y with AML within 6m of achieving CR2/CRp2, ineligible for allo-SCT due to any reason, with ≥300 lymphocytes/ul and with adequate renal and hepatic function. Subjects with central nervous involvement, having received a live vaccine 30d prior to first dose of study drug, having a diagnosis of immunodeficiency, receiving ≥10mg daily of prednisone equivalent (or any other systemic immunosuppressant) for any indication 7d prior to first dose of study drug, hypersensitivity to study agent and with a history of solid organ transplant would be excluded. The clinical trial is actively enrolling, and the registry number is NCT04229979 . Clinical trial information: NCT04229979.

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