SGR-3515 Wee1/Myt1 dual inhibitor shows manageable G3/4 AEs and 78% stable disease at 100–135mg in heavily pretreated solid tumors

SGR-3515 is an oral small-molecule dual inhibitor of the cell-cycle checkpoint kinases Wee1 and Myt1, designed to force CDK1 activation and disrupt G2/M control (synthetic-lethal rationale), and is being tested in the first-in-human SGR-3515-101 Phase 1 BOIN dose-escalation study (NCT06463340) with intermittent once-daily dosing in 28-day cycles. As of Oct 31, 2025, 33 participants with advanced solid tumors (predominantly ovarian cancer [n=20], ER+ breast [n=5], uterine [n=5]) and a median of 5 prior lines were treated across 15–175mg; any-grade/≥G3 TEAEs were 79%/37% and any-grade/≥G3 TRAEs were 64%/15%, with no Grade 5 events, no DLTs, and 1 drug-related discontinuation (Grade 3 LFT increase). Efficacy was early and response-light—stable disease in 8/23 (35%) evaluable overall, but 7/9 (78%) stable disease at 100–135mg with 6 still on treatment (median 165 days, range 110–292)—which roughly lands in the “disease control only” zone you often see with cytostatic agents in late-line PROC where single-agent PD-1 has low ORR (~4%–10%) and many single-agent cytotoxics deliver modest response rates and short PFS.