Successful induction of tumor-directed immune responses in high grade serious ovarian carcinoma patients after primary treatment using a whole tumor cell vaccine.

Abstract

5566 Background: Improving disease free and overall survival in advanced high grade serous ovarian carcinoma (HGSOC) after primary treatment remains challenging. This phase 1 trial (NCT04739527) evaluated safety and immunogenicity of a whole tumor cell vaccine, vididencel, to prime or boost immune responses in HGSOC after primary treatment. Vididencel expresses tumor associated antigens (TAA) frequently upregulated in HGSOC. Methods: Patients with advanced HGSOC who completed primary treatment received 6 intradermal injections with vididencel: 4 biweekly doses of 25 million cells (week 0, 2, 4 and 6) followed by 2 boosters of 10 million cells (week 14 and 18). Peripheral blood mononuclear cells were obtained at week 0, 4, 10, 14, 18 and 22. Disease status was evaluated at week 22 using clinical assessment and CA125 levels. Primary endpoint was safety and the induction of immune responses, measured by IFNy ELISPOT, to at least one TAA (i.e. WT-1, PRAME, NY-ESO, or MAGE-A3/4). Secondary endpoints were disease status at week 22 and survival. Results: Primary analysis at week 22 has been completed for all 17 patients. In total,16 received all 6 planned injections and 1 patient discontinued treatment after 4 injections due to disease progression. Vididencel showed in 12 out of 17 patients a vaccine-induced response (VIR) to at least one of the tested antigens and 7 of these patients showed a sustained immune responses to the same antigen (sVIR). Table 1 shows the distribution of induced immune responses. Five patients were also given maintenance treatment with PARP inhibitors and all these patients showed a VIR. Vididencel was well-tolerated, with no trAEs above grade 2. The most common trAEs were mild to moderate local injection site reactions, characterized by redness, swelling and inflammation. Two unrelated serious AEs occurred, both linked to disease progression. At week 22, 4 weeks after last vididencel treatment, 10 patients (59%) had stable disease, and 7 had progressive disease, with all patients still alive. Patients with a VIR or sVIR had a higher rate of SD than patients without a vaccine-induced immune response (67% and 71% versus 40%, respectively). Long-term follow of patients continues of which a swimmers plot will be shown. Conclusions: Vididencel is well tolerated and effective in eliciting or boosting a broad T-cell response in HGSOC patients after primary treatment. Short-term evaluation of clinical response at week 22 suggests better responses in patients developing a VIR or sVIR compared to those patients not having a detectable immune response to the vaccine. Clinical trial information: NCT04739527 . Immune response outcome (N=17) Responses to individual TAAs WT1 PRAME NY-ESO MAGEA3/A4 Immune responders(N=12) VIR (n=12) 6 of 12 3 of 12 4 of 12 7 of 12 sVIR (n=7) 4 of 7 2 of 7 1 of 7 2 of 7 Non-responders(N=5) No VIR (n=5) (s)VIR; (sustained) vaccine induced response.