Background: Low-grade serous (LGS) carcinomas of the ovary, fallopian tube and primary peritoneum are a unique subset of serous carcinomas for which current therapies (chemotherapy, hormonal) have demonstrated limited efficacy. KRAS or BRAF mutations, which activate the RAS/RAF/MEK/ERK signaling pathway, are present in many LGS carcinomas. Binimetinib is a potent inhibitor of MEK1/2, a key component of the RAS/RAF/MEK/ERK pathway, and has demonstrated activity in other disease settings where dysregulation of this pathway is present. Methods: This is a 2-arm, open-label, 2:1 randomized Phase 3 study of binimetinib vs physician’s choice chemotherapy (pegylated liposomal doxorubicin, paclitaxel or topotecan) in patients with LGS carcinomas. Eligible patients must have LGS carcinoma that is recurrent or persistent following at least 1 prior platinum-based chemotherapy and no more than 3 prior lines of chemotherapy, and must have RECIST v1.1-defined measurable disease confirmed by blinded independent central review (BICR). Prior to randomization, confirmation of LGS diagnosis is required. Patients are eligible regardless of RAS/RAF mutational status; however, tumor tissue will be retrospectively analyzed for mutations in RAS/RAF and other genes. Prior treatment with a MEK inhibitor or BRAF inhibitor is prohibited. Randomization is stratified by last platinum-free interval and number of prior systemic therapy regimens. The primary endpoint is progression-free survival as determined by the BICR; secondary endpoints include overall survival, overall response, duration of response, disease control rate, safety, quality of life and pharmacokinetics of binimetinib. Binimetinib is administered 45 mg BID orally. Patients receive therapy until disease progression or unacceptable toxicity. Crossover is permitted from physician’s choice chemotherapy to binimetinib upon BICR-confirmed progression. This study will enroll 300 patients worldwide (NCT01849874). Clinical trial information: NCT01849874