Introduction/Background Low-grade serous ovarian cancer (LGSOC) and adult-type granulosa cell tumor (aGCT) are rare ovarian malignancies, accounting for about 8% and 5% of all ovarian cancers, respectively. These subtypes of ovarian cancer will often be treated with conventional chemotherapy, although response rates are disappointing. Due to these low response rates, the search for alternative treatment strategies is crucial. The cyclin-dependent kinase 4/6 (CDK4/6) inhibitor abemaciclib in combination with an aromatase inhibitor (e.g. letrozole) has remarkably improved the outcome of patients with estrogen receptor-positive (ER+) breast cancer. ER+ ovarian cancer shows variable responses to aromatase inhibitors, which hopefully can be improved by the same drug combination.
Methodology The study is a phase 2, multicentre, open-label, single-arm clinical trial of abemaciclib (150 mg BD) and letrozole (2.5 mg OD) in patients with advanced, recurrent and/or metastatic ER+ ovarian cancer who failed one line of platinum-based chemotherapy for advanced or recurrent disease. One cohort will include LGSOC patients and another cohort aGCT patients. Up to 50 patients with ER+ tumors will be included per cohort. Enrolment will take place at 3 Belgian, 5 French, 5 Spanish and 3 Dutch sites. The primary objective of this study is to determine overall response rate to abemaciclib and letrozole, according to RECIST v1.1. Secondary objectives include DOR, CBR, PFS, OS and adverse events. Additionally, patient-reported quality of life will be assessed by applying EQ-5D-5L and EORTC QLQ-C30 questionnaires. Exploratory aims include assessing blood and tissue biomarkers (such as ER, PR, ctDNA, mutation burden, methylation signatures etc.) for association with clinical benefit and response rate. An interim analysis will be performed at week 24 to assess efficacy after 15 patients per cohort become evaluable. Thirty additional patients per cohort will be included when the response rate is more than 1 in 15 evaluable patients.
Disclosures This trial is supported by Eli Lilly and Company which supplies the study drug abemaciclib and Kom Op Tegen Kanker (Stand Up Against Cancer) which provides a grant.
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