Ctni-61. Preliminary Results of a Phase I/ii Trial of Selinexor and Temozolomide in Recurrent Glioblastoma
Year: 2024
Type: conference-abstract
Abstract: BACKGROUND Selinexor (SEL) is a first-in-class XPO1 inhibitor with potent antitumor activity through the nuclear retention and reactivation of tumor suppressor proteins, reduced translation of oncogenes, and decreased expression of anti-apoptotic proteins. As a single agent, SEL has demonstrated brain penetration and clinically relevant responses in glioblastoma. We seek to enhance the effect and benefit of SEL by priming with temozolomide (TMZ). METHODS Through an NCI Project Team, we developed a multi-institutional phase I/II clinical trial which opened across the NCI Experimental Therapeutics Clinical Trial Network. Eligibility included histologically confirmed 1st recurrent MGMT promoter methylated glioblastoma. We evaluated safety, tolerability, and dose finding with an IQ 3 + 3 design of TMZ 150mg/m2 on days 1-5 of a 28-day cycle plus SEL on days 8 and 15. RESULTS From October 2022 to March 2024, we enrolled 12 patients (n=11 evaluable) into phase I of the study. Patient characteristics included 82% male, median age 62 (range 50-77), 64% white. The median number of cycles administered was 6 (range 1-12). Two dose levels (SEL 60mg and SEL 80mg) were evaluated. No dose-limiting toxicities (DLTs) were observed. The most common treatment related adverse events were nausea (58%), decreased platelet count (50%), fatigue (50%), constipation (42%), vomiting (25%), decreased lymphocyte count (25%), and decreased neutrophil count (25%). Grade 3+ treatment related adverse events included nausea, grade 3 (n=1); decreased lymphocyte count, grades 3-4 (n=2); and anorexia, grade 3 (n=1). Phase I has completed enrollment and the recommended phase II dose will be SEL 80mg. Additional results will be presented. CONCLUSION Results suggest that a sequential dosing regimen of SEL+TMZ is feasible, well-tolerated, and may minimize the cumulative toxicity of SEL. The phase II randomized portion of this trial is enrolling nationwide and will investigate efficacy and candidate molecular signatures of vulnerability (NCI #10505, NCT05432804).
Source: Neuro-Oncology
Authors: Frances Chow, Michael Berens, Joycelynne Palmer, Miguel Villalona-Calero, Douglas Ney, Macarena De La Fuente, Kurt Jaeckle, Sani H Kizilbash, Ruham Alshiekh Nasany, Maya Hrachova, Alyx B Porter, David Piccioni, Kimberly Hoang, Lindsay Lipinski, Roy Strowd, Pierre Giglio, Megan Mantica, David Schiff, Steven Gore, Jana Portnow
Institutions: University of Southern California, Translational Genomics Research Institute, City Of Hope National Medical Center, University of Miami, Sylvester Comprehensive Cancer Center, Mayo Clinic in Florida, Mayo Clinic, University of Oklahoma Health Sciences Center, University of California San Diego, Winship Cancer Institute, Roswell Park Comprehensive Cancer Center, Wake Forest University Health Sciences, The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University, UPMC Hillman Cancer Center, University of Virginia Cancer Center, National Cancer Institute
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W4404236967