Background: Treatment options for patients with high-grade ovarian serous (HGSC) or endometrioid carcinoma (HGEC) who progress after receiving chemotherapy for recurrence are limited. Methods: LACOG 1018, a phase II, single-arm, multicenter trial evaluated the efficacy of letrozole 2.5mg/day po continuously plus palbociclib 125mg/day po for 21 days in 28-day cycles in patients with histologically proven ovarian HGSC or HGEC, fallopian tube or peritoneal cancer who had progressed on prior chemotherapy for locoregional recurrence or metastatic disease (at least one platinum-based regimen). Patients had centrally confirmed ER and/or PR positivity (> 10% by immunohistochemistry) and ECOG PS 0-2. The primary endpoint was progression-free survival (PFS) at 12 weeks by RECIST 1.1. Secondary endpoints were overall survival (OS), overall response rate (ORR), clinical benefit rate (CBR) and safety. Tumor evaluations were performed every 6 weeks until week 24. Sample size was calculated as 31 patients for the primary endpoint (90% power to detect a two-sided significance level of 5%, 45% PFS at 12 weeks) and 39 patients for secondary endpoints considering 10% drop-out. NCT03936270. Results: A total of 41 eligible patients were included in five Brazilian centers between Feb2020-Jan2022 (table). The PFS-week12 rate was 63.4% (95%CI 46.8 – 76.1). At the time of analysis (cut-off date Jan 18th, 2023) median follow-up was 18.1 months (95%CI 12.9 – 24.3), and 37 PFS events had occurred. Median PFS was 4.2 months (95%CI 2.7 – 5.5) and median OS was 13.4 months (95%CI 10.4 – 20.1). The ORR was 7.7% (N=3 PR) and the CBR was 71.8%. Treatment-related adverse event rates of any grade and grade 3-4 were 95.1 % and 51.2 %, respectively. Grade 3-4 neutropenia was reported in 17 (41.5%) patients, and febrile neutropenia in 1 (2.4%). Only one patient (2.4 %) discontinued the treatment due to toxicity. At the cut-off date, three patients remained on treatment. Conclusions: Palbociclib combined to letrozole demonstrated a significant efficacy in terms of PFS rate at 12 weeks (63.4%) and CBR (71.8%), with no new safety concerns in women with recurrent advanced and metastatic hormone receptor-positive ovarian cancer. These results warrant further investigation of palbociclib plus letrozole in high-grade ovarian cancer. Clinical trial information: NCT03936270.