Background: We recently reported on the efficacy of the p62/SQTM1-encoding plasmid in patients with advanced, recurrent platinum-resistant ovarian cancer (PROC) receiving gemcitabine chemotherapy. Here we analyze the effects of baseline prognostic factors on efficacy. Methods: A prospective multicenter randomized study took place between 01/2020 and 08/2023. Cohort A (n=20) consisted of Gemcitabine 1000 mg/m2 days 1,8 every 3 weeks and Cohort B (n=20) consisted of Gemcitabine (Gem) 1000 mg/m2 days 1,8 every 3 weeks plus p62-plasmid 2.5 mg i.m. weekly. We stratified the patients into subgroups according to their baseline CA-125 level (normal vs high), number of lines of chemo (1 vs 2-3) received by a platinum-sensitive ovarian cancer (PSOC) patient before they became PROC, platinum-free interval (PFI) (up to 3 mo vs more than 3 mo), and presence or absence of peritoneal effusion. Cox proportional hazards regression analysis was utilized to determine effect of progression free survival (PFS). Results: The median follow-up was 13.8 months (mos). The median PFS was 2.8 mos in Gem (Arm A) and 7.2 mos in Gem + Plasmid (Arm B) respectively (p = 0.03). The overall response rate (ORR) by RESIST 1.1 was higher in the Gem +Plasmid arm: partial response (PR) - 5.0% and 20.0%, stable disease (SD) - 40.0% and 60.0%, and disease control rate 41.2 and 80% in Chemo and Plasmid arms respectively). In cohort A, all patients have progressed, whereas in Cohort B (Gem +Plasmid) 9 patients (45%) remained progression-free with the longest duration of response being 30 mo. Overall survival cannot be assessed yet. Analyzing prognostic factors with Cox Proportional Hazards Regression Analysis identified that the following factors increase p62 sensitivity: initial high CA-125 level PFS 2.5 and 6.5 (p = 0.01) in Arm A vs B, 1 line chemo vs 2 or 3 lines for PSOC, PFS 2.3 and 7.1 (p = 0.008) in Arm A vs B, and presence of peritoneal effusion PFS 2.4 and 7.6 (p = 0.008) in Arm A vs B (Table ). Conclusions: We observed maximal effect on PFS when combining the p62-encoding plasmid with Gem in the patients with the most dismal prognosis PROC: rapid progression (relapse as PROC after the first line of treatment and/or short PFI), in patients with an initial high level of CA-125, and/or pleural effusion.