Ovarian cancer (OvCa) is the most lethal gynecological malignancy with an annual incidence of >300,000 and a mortality of 200,000 worldwide (Sung et al 2020). Survival rates have only shown marginal improvement over the past decades with a 5-year survival of ~30-35% in advanced cases (Howlader et al 2020).
The initial treatment of ovarian cancer involves surgery and platinum-based chemotherapy. The majority of patients respond well to initial therapy but the risk of recurrence is high and most patients will develop platinum-resistant disease with clinical response rates of ~10-20% to any additional therapies (Davis et al 2014, van Zyl et al 2018, Hamanishi et al 2015, Garcia et al 2013). The limited effective and well-tolerated options beyond platinum-based therapies justify the need for new treatments to improve both outcome and quality of life of patients.
Maveropepimut-S (MVP-S) uses the DPX platform, a non-aqueous, lipid-based delivery system, to educate a specific and persistent immune response to 5 HLA-restricted peptides of survivin, a cancer-associated protein commonly upregulated in advanced OvCa. In a prior study in patients with advanced, metastatic recurrent ovarian cancer, MVP-S with low-dose cyclophosphamide (CPA) led to clinical responses, durable benefit, and persistent, survivin-specific T cells. Treatment was well-tolerated. Further exploration of the regimen in platinum resistant ovarian cancer is warranted to confirm and extend these initial results.
The AVALON study (NCT05243524) is a phase 2b, single-arm trial assessing the efficacy and safety of subcutaneous MVP-S in combination with low-dose oral CPA. Eligible patients have recurrent platinum resistant OvCa, ≤4 lines of prior OvCa therapy, and no single lesion >4 cm. The primary endpoint is objective response rate (ORR) per RECIST 1.1 and secondary endpoints include ORR per iRECIST, disease control rate, duration of response, and survival rates. Exploratory objectives include characterization of MVP-S induced immune responses in peripheral blood and the tumor microenvironment of paired tissue samples. The study will enroll 73 subjects in North America and Europe.
NCT05243524