184 UPLIFT (ENGOT-ov67/GOG-3048) a pivotal cohort of upifitamab rilsodotin, a NaPi2b-directed ADC in platinum-resistant ovarian cancer

Abstract

<h3>Introduction/Background*</h3> Upifitamab rilsodotin (XMT-1536; UpRi), is a first-in-class Dolaflexin antibody-drug conjugate targeting NaPi2b, a sodium-dependent phosphate transport protein broadly expressed in solid tumors including high-grade serous epithelial ovarian cancer (OC). UpRi’s safety and efficacy are being evaluated in a Phase I study (NCT03319628). Preliminary antitumor activity from an expansion cohort of heavily-pretreated OC patients has been reported (Hamilton et al, ESMO 2020). A data-cut of December 2020 demonstrated an ORR of 39% including 2 CRs and DCR of 81% in 26 OC patients with high NaPi2b expression (TPS ≥75). The 2 patients achieving CR had previously been treated with bevacizumab and PARPi (Richardson et al, ASCO 2021, TPS5607). The prevalence of a TPS ≥75 is greater than 60%. PROC remains a serious unmet medical need as available treatment options provide modest benefit of no more than 12% ORR and median OS less than 12 months. Based on encouraging anti-tumor activity of UpRi, UPLIFT was designed as a Phase 2 single-arm registration strategy for PROC as part of the ongoing study. <h3>Methodology</h3> The UPLIFT cohort is enrolling patients with platinum resistant high grade serous ovarian, fallopian tube and primary peritoneal cancer with up to 4 prior lines of therapy. Prior bevacizumab is required for patients with 1 or 2 prior lines of therapy but is not required for patients with 3-4 prior lines of therapy. UPLIFT will enroll approximately 180 patients globally for 100 patients with high NaPi2b expression. UpRi is dosed intravenously at 43 mg/m2 every 4 weeks. Patients may enroll regardless of NaPi2b expression and regardless of baseline peripheral neuropathy. Baseline tumor samples (fresh or archived) will be collected for retrospective tumor tissue evaluation of NaPi2b expression. <h3>Result(s)*</h3> The primary objective is assessment of objective response rate in patients with high NaPi2b expression. The cut-off for high NaPi2b expression is TPS ≥75 and was based on data from the expansion cohort. Secondary endpoints include objective response rate in the overall population, duration of response, and adverse events. <h3>Conclusion*</h3> This study is being conducted in collaboration with ENGOT and GOG. Patients will be enrolled globally. (NCT03319628).