Updated efficacy of dalpiciclib and nonsteroidal aromatase inhibitors (NSAIs) in estrogen receptor–positive (ER+) recurrent/metastatic (R/M) ovarian cancer and uterine neoplasms.

5559 Background: Initial results from our trial showed the anti-tumor activity and good tolerance of CDK4/6 inhibitor dalpiciclib combined with NSAIs in patients (pts) with ER+ R/M ovarian cancer and uterine neoplasms (SGO, 2024, #S283; IGCS, 2025, #397). Here, we report updated results. Methods: This single-center, single-arm, open label, phase 2 trial enrolled pts with ER+, R/M ovarian cancer and uterine neoplasms which met the following criteria: pretreated low-grade serous ovarian carcinoma (LGSOC), pretreated uterine endometrioid carcinoma (EC), uterine leiomyosarcoma (LMS), or untreated low-grade endometrial stromal sarcoma (LGESS). Pts received dalpiciclib (150mg po d1-21 q28d) and NSAIs (mainly letrozole 2.5mg po qd) until disease progression, unacceptable toxicity or consent withdrawn. The primary endpoint was 12-week progression-free survival (12wPFS) rate. A Simon’s two-stage design was used (one-sided α=0.05, power=80%), and the null hypothesis (P0=0.2) would be rejected if totally >10 of 33 pts achieved primary endpoints. Results: As the data cutoff (Jan 5, 2026), 35 pts with a median of one prior therapy for R/M disease were enrolled, including 11 with LGSOC, 15 with EC, 8 with LGESS and 1 with LMS. With a median follow-up of 11.4 months (range, 0.1-52.2), 22 of 29 efficacy-evaluable pts had reached the primary endpoint, with a 12wPFS rate of 75.9% (95% CI 56.5-89.7), suggesting the value of further investigation. Detailed efficacy results are shown in Table 1. Grade 3-4 treatment-related adverse events (TRAEs) occurred in 82.9% (29/35) of pts, mostly neutrophil count decreased (71.4%), white blood cell count decreased (45.7%) and platelet count decreased (14.3%). Sixteen pts had dose reduction of dalpiciclib, mostly due to hematologic toxicities. No serious adverse events or treatment-related deaths occurred. Twelve pts were still on-treatment, with 3 pts treated for >4 years. Conclusions: The trial achieved its positive primary endpoint, showing meaningful efficacy of dalpiciclib + NSAIs in ER+ R/M ovarian cancer and uterine neoplasms. No new safety signals were observed. Clinical trial information: ChiCTR2000040597. Efficacy results of evaluable pts. OverallN=29 LGSOCn=9 ECn=11 LGESSn=8 LMSn=1 12wPFS rate[95%CI] 75.9% (22/29)[56.5-89.7] 77.8% (7/9)[40.0-97.2] 63.6% (7/11)[30.8-89.1] 100% (8/8)[63.1-100] 0% (0/1)[0-97.5] Clinical Response Partial response (PR) 5 (17.2%) 1 (11.1%) 2 (18.2%) 2 (25.0%) 0 (0%) Stable disease (SD) 17 (58.6%) 6 (66.7%) 5 (45.5%) 6 (75.0%) 0 (0%) SD≥24 weeks 14 (48.3%) 5 (55.6%) 4 (36.4%) 5 (62.5%) 0 (0%) Progressive disease (PD) 7 (24.1%) 2 (22.2%) 4 (36.4%) 0 (0%) 1 (100%) ORR (CR+PR, 95% CI) 17.2% (5.85-35.8) 11.1% (0.28-48.3) 18.2% (2.28-51.8) 25.0% (3.19-65.1) 0% (0-97.5) CBR (CR+PR+SD≥24 weeks, 95% CI) 65.5% (45.7-82.1) 66.7% (29.9-92.5) 54.5% (23.4-83.3) 87.5% (47.4-99.7) 0% (0-97.5)