Background: Platinum-refractory or platinum-resistant ovarian cancer remains unmet medical need with an unfavorable prognosis. Its treatment options are limited and sequentially with multiple single-agent regimens or bevacizumab plus single-agent regimens are recommended. Mitoxantrone hydrochloride liposome (PLM60) is the first approved mitoxantrone nano-drug, which has shown favorable pharmacokinetic characteristics with long circulation and high cumulation in tumor tissue, thus has a promising anti-tumor activity. This trial aimed to explore the efficacy and safety of PLM60 in patients with platinum-refractory or platinum-resistant ovarian cancer. Methods: In this multi-center, open-label, single arm study, patients with histologically confirmed, epithelial ovarian, fallopian tube, or primary peritoneal carcinoma, either platinum-refractory or platinum-resistant, with at least one measurable lesion were recruited. PLM60 20 mg/m² was administered on day 1 of each 21-day cycle for up to 8 cycles treatment or until disease progression or intolerable toxicities. The primary endpoint was safety, adverse events were graded according to CTCAE 5.0. Second endpoint included overall response rate (ORR), duration of response (DoR), disease control rate (DCR), progression free survival (PFS) and overall survival (OS) as per RECIST 1.1. Results: 47 eligible patients with a median age of 54 years (range, 35-67) were treated in 7 institutions in China, including 15 platinum-refractory patients and 32 platinum-resistant patients. 32 (68.1%) of 47 patients received at least 3 prior lines of therapy. Treatment related adverse events (TRAEs) of any grade occurred in 45 (95.7%) of 47 patients, in which 31 (66.0%) were ≥ grade 3. The most common ≥ grade 3 TRAEs (incidence ≥10%) were leucopenia (51.1%), neutropenia (40.4%), anemia (19.1%), lymphocytopenia (17.0%) and thrombocytopenia (17.0%). At the cut-off data of October 31 2021, 39 patients were evaluable for response. ORR was 17.9% (7/39, 95% CI:7.5-33.5%, 7 PRs) and DCR was 56.4% (22/39, 95% CI:39.6-72.2%, 15 SDs). Among 21 platinum-resistant patients with ≥3 prior lines, the median DoR was 4.6 month, 2 responders had a DoR of > 6 months. The ORR and DCR of this cohort were 28.6% (6/21, 95% CI: 11.3-52.2%, 6 PRs) and 61.9% (13/21, 95% CI: 38.4-81.9%, 7 SDs), respectively. Median PFS was 3.6 month (95% CI 1.4-4.6), OS data was not mature. Objective response was not observed in platinum-refractory patients. Conclusions: PLM60 had an encouraging efficacy especially in platinum-resistant patients who had received at least 3 prior lines with tolerable safety profiles. Clinical trial information: NCT04718376.