Updated efficacy, safety, and exploratory biomarker analyses of a phase II trial of abemaciclib plus hormonal therapy in recurrent ovarian (OC) and endometrial cancer (EC).

Abstract

5516 Background: We evaluated abemaciclib with hormonal therapy in patients with estrogen receptor positive (ER+) EC, low-grade serous OC (LGSOC), and selected high-grade serous OC (HGSOC) with CDK4/6 molecular activation features in a single-center, phase II study. Preliminary results demonstrated a 24-week progression-free survival (PFS) rate of 53% in ER+ EC and 60% in LGSOC (2025 SGO Abstract 256). Here, we report the final clinical outcomes and present the first exploratory biomarker analyses from this study. Methods: Abemaciclib was administered at 150mg twice daily in combination with hormonal therapy. The primary endpoint was 24-week PFS; secondary endpoints were median PFS (mPFS), disease control rate (DCR), objective response rate (ORR) and safety. Exploratory analyses evaluated efficacy by TCGA molecular subgroups and tumor next-generation sequencing–defined alterations. PFS was estimated using Kaplan–Meier and compared using log-rank. Results: As of December 2, 2025, 43 patients (21 HR+ EC, 14 LGSOC, 8 HGSOC) were evaluable, with a median follow-up of 29 months (mos). Median age was 64 (range 24-78) and median prior lines of therapy was 3 (range 1-13). Among 21 patients with ER+ EC, the 24-week PFS rate was 56.1% (95% CI 34.5–77.7), mPFS was 9.0 mos (2.4–11.3), DCR was 63%, and ORR was 21%, including one complete response. There were 13 (62%) NSMP, two (10%) MSI-high, two (10%) TP53-abnormal, one (5%) POLE-mutated, and three without molecular data. The NSMP group had 24-week PFS rate and mPFS of 59.8% (32-87.3%) and 10.4 mos (2.4-21.0), compared with 20.0% (0-55.0) and 1.9 mos (1.7-9.3) in the non-NSMP group (p=0.02). Notably, all responses occurred in the NSMP group. The largest difference was observed between patients with CTNNB1mut with a mPFS of 10.4 months (1.9–NR) compared with 5.2 mos (1.7–9.3) in patients with CTNNB1wt ( p = 0.22). Among 14 patients with LGSOC, the 24-week PFS rate was 71.4% (47.8-95.1), mPFS was 17.5 mos (3.5-NR), DCR was 79% and ORR was 14%, 5 still on treatment at data cut off. The median time on treatment was 10.5 mos (range 1.7-55.4), 4 patients (28%) were on treatment for more than 3 years, the longest still on treatment after 4.6 years. The most common mutation was KRAS in 7 (50%), with no observed differences by KRAS status (KRASmut 11.9 mos [1.9-NR] mPFS, KRASwt 17.5 mos [3.5-NR] mPFS , p=0.89). Despite the 8 patients with HGSOC having CDK4/6 activating mutations the 24-week PFS rate was 12.5% (0-35.4) and the mPFS was 1.6 mos (0.3-1.9). No new safety signals were observed across all subgroups. Conclusions: Abemaciclib demonstrated promising clinical activity in patients with LGSOC regardless of KRASmut status and in ER+ EC, with the greatest activity observed in the NSMP group and potentially CTNNB1-mutated cases; however, these exploratory subgroups need larger validation. Clinical trial information: NCT04469764 .