Abstract 861: N17350 outperforms cytotoxic agents in killing tumors of treatment-naïve and chemotherapy-treated ovarian carcinoma patients

Abstract Background: Tumor heterogeneity leads to suboptimal responses to chemotherapy as well as primary and acquired resistance. Advanced ovarian cancer (OvCA) patients with chemotherapy resistant disease have significantly poorer prognosis and limited treatment options and thus there is an urgent need for new therapies. N17350 is a novel therapeutic modality that kills cancer cells independent of anatomical locations, tumor genetics, and tumor immune status while preserving normal cells. N17350’s broad efficacy and specificity are mediated by elevated levels of histone H1 isoforms in cancer cells. A single intra-tumoral injection of N17350 induces tumor regression and triggers anti-tumor immunity in a wide range of pre-clinical models [1 - 4]. Here, we compared tumor killing by N17350 to standard-of-care chemotherapies in vitro and in vivo in OvCa patients that had not received chemotherapy or received neoadjuvant chemotherapy (NACT) prior to cytoreductive surgery. Methods: Cytoreductive surgery tissue specimens were collected from 27 consecutive patients treated by author AB. Cancer cells and CD45+ immune cells were isolated, treated with N17350 24h post-isolation, and cell viability was quantified by calcein-AM and immunogenic cell death markers. In vitro tumor killing by N17350 was compared to carboplatin, paclitaxel, doxorubicin, or oxaliplatin in chemotherapy naïve and NACT patients. OvCa cells from 3 patients were injected into nude mice to create cell-derived xenograft (CDX) models. Mice were treated with N17350 (400μg/100mm3, intratumoral) or carboplatin (100mg/kg, intraperitoneal) and tumor growth was assessed. Results: Of 27 patients, 18 had OvCa, 9 had peritoneal carcinoma, 1 had fallopian carcinoma, 1 had high-grade invasive squamous cell carcinoma and 1 had sarcoma. 15 were chemotherapy naïve prior to cytoreduction, 11 received 3-7 cycles of NACT, and 1 had recurrent disease. N17350 induced immunogenic cell death in cancer cells and preserved immune cells in all tested patients, whereas chemotherapies were toxic to both cell types equally. N17350 was more effective at killing cancer cells than chemotherapy in patients with NACT. Additionally, N17350 showed robust tumor killing in primary, metastatic, and recurrent tumors whereas chemotherapy was inferior in killing metastatic and recurrent tumors. N17350 rapidly regressed tumors in all OvCa CDX models and exhibited markedly improved efficacy over carboplatin. Conclusions: Our data demonstrate that, compared to standard chemotherapy, N17350 yields superior and more selective tumor killing, particularly following exposure to NACT. Tumors that are resistant to chemotherapy retain sensitivity to N17350, and N17350 could improve clinical outcomes in OvCa, including patients with chemotherapy resistant disease. Citation Format: Chang Cui, Ravindra Gujar, Maria Fumagalli, Nicole Martinez, Peter Haberz, Afshin Bahador, Alain Algazi, Lev Becker. N17350 outperforms cytotoxic agents in killing tumors of treatment-naïve and chemotherapy-treated ovarian carcinoma patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 861.