Phase 1b REC-617 selective CDK7 inhibitor (transcription/cell-cycle kinase target) in RB1– LMS

MD Anderson Cancer Center is running this Phase 1b, single-group, open-label study to test whether REC-617—an oral small-molecule inhibitor of CDK7 (a cyclin-dependent kinase that supports transcriptional regulation and cell-cycle progression)—can control metastatic or unresectable leiomyosarcoma that is RB1-negative by IHC (0% staining cutoff). Patients must have had at least one prior systemic therapy line (so a typical 2nd-line+ setting) and have measurable disease by RECIST 1.1; the trial also requires lesions amenable to biopsy (excluding bone) for pharmacodynamic and response workups. The intervention is continuous REC-617 10 mg once daily, with endpoints including objective response rate plus clinical benefit rate, PFS, OS, and CTCAE toxicity. The drug is owned/developed by Recursion Pharmaceuticals, while the trial is sponsored by MD Anderson, reflecting an academic-center expansion into a genomically/biologically defined LMS subset (RB1 loss is common in LMS, but not universal). Today’s care after progression is sequential systemic therapy such as doxorubicin-based regimens up front, then options like gemcitabine/docetaxel, trabectedin, pazopanib, eribulin, or dacarbazine-based therapy, with responses often limited—so this tests whether CDK7 dependence in RB1– disease can be exploited with a targeted oral agent.