SARC041: A phase 3 randomized double-blind study of abemaciclib versus placebo in patients with advanced dedifferentiated liposarcoma.

person Mark Andrew Dickson Memorial Sloan Kettering Cancer Center, New York, NY info_outline Mark Andrew Dickson, Karla V. Ballman, Mia C. Weiss, Steven Attia, Michael J Wagner, Seth Pollack, Edwin Choy, Andrew J. Wagner, Breelyn A. Wilky, Lara E. Davis, Richard F. Riedel, William D. Tap

Authors person Mark Andrew Dickson Memorial Sloan Kettering Cancer Center, New York, NY info_outline Mark Andrew Dickson, Karla V. Ballman, Mia C. Weiss, Steven Attia, Michael J Wagner, Seth Pollack, Edwin Choy, Andrew J. Wagner, Breelyn A. Wilky, Lara E. Davis, Richard F. Riedel, William D. Tap Organizations Memorial Sloan Kettering Cancer Center, New York, NY, Weill Cornell Medicine, New York, NY, Washington University School of Medicine, St. Louis, MO, Mayo Clinic, Jacksonville, FL, University of Washington, Seattle, WA, Northwestern University, Chicago, IL, Massachusetts General Hospital, Boston, MA, Dana-Farber Cancer Institute, Boston, MA, University of Colorado Anschutz Medical Campus, Aurora, CO, Knight Cancer Institute, Oregon Health & Science University, Portland, OR, Duke Cancer Institute, Durham, NC, Sarcoma Medical Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Eli-Lilly Background: Recurrent or metastatic dedifferentiated liposarcoma (DDLS) remains a difficult disease to treat. Available agents such as doxorubicin, eribulin, trabectedin, ifosfamide, dacarbazine, or gemcitabine-based regimens are associated with low response rates and only modest improvements in progression free or overall survival. The oncogene CDK4 is ubiquitously amplified in this disease and represents a rational therapeutic target. In single-arm phase 2 studies, treatment with selective CDK4 inhibitors resulted in clinical benefit (12-week progression-free survival (PFS) of 57% with palbociclib and 74% with abemaciclib). We hypothesize that treatment with abemaciclib will improve PFS compared to placebo in patients with recurrent or metastatic DDLS. Methods: This is a phase 3 randomized double-blind study of abemaciclib versus placebo. Eligible patients have recurrent or metastatic dedifferentiated liposarcoma (purely well-differentiated liposarcoma excluded), progression of disease by RECIST 1.1 in the 6 months prior to study entry, any number of prior systemic therapies, and adequate organ function and performance status. Patients are stratified by number of prior lines of therapy (0 vs 1 or more) and randomized 1:1 between abemaciclib 200 mg PO twice a day and matching placebo. Patients are followed with scans every 6 weeks (every 12w after 36w) and those with progression of disease on placebo may cross over to open label abemaciclib. The primary endpoint is PFS. Target enrollment is 108 evaluable patients which provides 80% power with two-sided 10% significance level to detect a hazard ratio of 0.6. Secondary endpoints include response rate, PFS and response rate after crossover, and overall survival. Archival tissue will be collected to explore potential biomarkers. As of Feb 1, 2023, 43 patients have been accrued at 9 participating centers. Clinical trial information: NCT04967521.

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