TP036/#426 Uplift (ENGOT-OV67/GOG-3048) a pivotal cohort of the XMT-1536–1 trial of upifitamab rilsodotin (XMT-1536; UPRI), a NAPI2B-directed antibody drug conjugate (ADC) in platinum-resistant ovarian cancer. (4th December 2022)

• Record Type: Journal Article
• Authors: Richardson, Debra; Perez Fidalgo, Jose Alejandro; Gonzalez-Martin, Antonio; Oaknin, Ana; Hamilton, Erika; Hays, John; Pothuri, Bhavana; Papadopoulos, Kyriakos; Taylor, Sara; Huang, Marilyn; Lee, Yeh-Chen; Krivak, Thomas; Moreno-Garcia, Victor; Calvo, Emiliano; Randall, Leslie; Starks, David; Ross, Malcom; Duska, Linda; Gao, Bo; Poka, Robert; Putiri, Emily; Barrett, Jamie; Demars, Leslie; Concin, Nicole
• Is Part Of: International journal of gynecological cancer. Volume 32(2022)Supplement 3
• Page Start: A241
• Page End: A241
• Publication Date: 2022-12-04
• Subjects: Generative organs, Female -- Cancer -- Periodicals; 616.99465
• DOI: 10.1136/ijgc-2022-igcs.545
• Languages: English
• ISSNs: 1048-891X

Abstract

Abstract : Objectives: UpRi is a first-in-class NaPi2b ADC with a novel scaffold-linker-payload that enables high drug-to-antibody ratio and controlled bystander effect. NaPi2b is a sodium-dependent phosphate transporter protein broadly expressed in high-grade serous ovarian cancer (HGSOC), with limited expression in healthy tissues. Interim data from the Phase 1b expansion cohort of heavily pretreated patients with recurrent HGSOC has been reported. These data demonstrated clinically meaningful activity, notably in patients with NaPi2b-high tumors (TPS≥75). Effective and well-tolerated treatments for PROC remains an unmet medical need. The standard of care, single-agent chemotherapy, has limited efficacy, significant toxicities, and short duration of response. UPLIFT was designed as a single-arm Ph2 registrational trial for UpRi monotherapy in PROC. Methods: UPLIFT is enrolling patients with PROC with up to 4 prior LoT. Prior bevacizumab is required for patients with 1–2 prior LoT only; it's not required for patients with 3–4 prior LoT. Patients may enroll regardless of NaPi2b expression; ≤ Grade 2 peripheral neuropathy is permitted. Primary platinum refractory patients are excluded. UPLIFT will enroll ~180 patients globally, including ~100 patients with high NaPi2b expression. UpRi is dosed IV at 36 mg/m 2 up to ~80 mg dose maximum Q4W. Baseline tumor samples (fresh or archived) will be collected for central analysis of NaPi2b expression. The primary endpoint is ORR in NaPi2b-high expressing patients. The cut-off for high NaPi2b expression is TPS≥75. Secondary endpoints include ORR in the overall population, duration of response, and safety. UPLIFT is conducted in collaboration with ENGOT (ENGOT-ov67) and GOG (GOG-3048). NCT03319628 Results: trialinprogress Conclusions: trialinprogress