538P Adding plasmid encoding p62/SQSTM1 to gemcitabine chemotherapy increases PFS for patients with platinum-resistant ovarian cancer (updated data)

Here we report the results of the second interim analysis of a randomized prospective multi-center clinical study aimed to evaluate safety and efficacy of p62/SQTM1-encoding plasmid applied as an adjuvant to chemotherapy in patients with advanced platinum-resistant ovarian cancer. P62 encoding plasmid acts as an classic anti-cancer DNA vaccine and it also lowers chronic inflammation thus rendering tumor cells more susceptible to immune response and chemotherapy. A prospective randomized study was started in 2020. Chemotherapy (Gemcitabine 1000 mg/m2 days 1,8 every 3 weeks) was administered in both arms. In the Chemo arm (n = 20) it was the only treatment, and in the Plasmid arm (n = 20) the same chemo was supplemented with p62-plasmid (2.5 mg i.m. weekly). To data cut-off, the median follow-up was 11.1 months in Efficacy-Evaluable Set. The median progression-free survival (PFS) was 2.7 and 6.6 mo in Chemo and Plasmid arms respectively (p Log-Rank = 0.018). Noteworthy, as of today, 35% of patients in the plasmid group did not progress with the longest PFS recorded so far is 24 months. The tumor response was assessed according to the RECIST 1.1 criteria. No complete responses were observed in either group. The objective response rate was higher in the Plasmid arm: partial response (PR) - 5.0% and 20.0%, stable disease (SD) - 40.0% and 60.0%, disease progression - 55.0% and 20.0%, and disease control rate (PR and SD) - 45.0% and 85.0% in Chemo and Plasmid arms respectively (p = 0,001). One patient in the Plasmid arm underwent complete cytoreduction with no evidence of disease progression. No Grade 3-4 toxicities were observed in both arms. All adverse effects were managed by conventional medications. No treatment delays or interruptions due to plasmid-related adverse events were registered. The interim results of this study show that adding p62/SQSTM1-encoding plasmid to standard Gemcitabine chemotherapy for advanced platinum-resistant ovarian cancer is a novel treatment approach which is safe, well-tolerated and effective: it improves ORR, DCR, and PFS. The long-lasting PFS in some patients is typical for immunotherapeutic agents. The study is ongoing.