Study of ELU001, a C’Dot drug conjugate (CDC) targeting folate receptor α (FRα) overexpressing solid tumors.

person Wen Wee Ma Cleveland Clinic, Cleveland, OH info_outline Wen Wee Ma, Anthony W. Tolcher, Cesar Augusto Perez, Andrea Elisabeth Wahner Hendrickson, Douglas W. Orr, Yonina R. Murciano-Goroff, Carey K. Anders, Erika P. Hamilton, Elizabeth M. Swisher, Cara Amanda Mathews, Babar Bashir, Luis Alexander Rojas-Espaillat, Gerardo Colon-Otero, Gregory Paul Adams, Catherine W. Reddick, Eliel Bayever

Authors person Wen Wee Ma Cleveland Clinic, Cleveland, OH info_outline Wen Wee Ma, Anthony W. Tolcher, Cesar Augusto Perez, Andrea Elisabeth Wahner Hendrickson, Douglas W. Orr, Yonina R. Murciano-Goroff, Carey K. Anders, Erika P. Hamilton, Elizabeth M. Swisher, Cara Amanda Mathews, Babar Bashir, Luis Alexander Rojas-Espaillat, Gerardo Colon-Otero, Gregory Paul Adams, Catherine W. Reddick, Eliel Bayever Organizations Cleveland Clinic, Cleveland, OH, NEXT Oncology, San Antonio, TX, Sarah Cannon Research Institute at Florida Cancer Specialists, Orlando, FL, Mayo Clinic Department of Medical Oncology, Rochester, MN, Mary Crowley Cancer Research, Dallas, TX, Memorial Sloan Kettering Cancer Center, New York, NY, Duke University Cancer Institute, Durham, NC, Sarah Cannon Research Institute, Nashville, TN, University of Washington School of Medicine, Seattle, WA, Women and Infants Hospital, Providence, RI, Thomas Jefferson University, Philadelphia, PA, Avera Cancer Institute, Sioux Falls, SD, Mayo Clinic Florida, Jacksonville, FL, Elucida Oncology, Monmouth Junction, NJ Abstract Disclosures Research Funding No funding sources reported Background: ELU001, pasifolate exatecan, is an ultra-small nanoparticle drug conjugate, known as a CDC (~6 nm), designed to target and penetrate into solid tumors. Due to its size, ELU001 exhibits rapid renal elimination which is expected to reduce or eliminate the toxicities associated with many antibody drug conjugates. ELU001 has ~13 folic acid targeting moieties and ~21 cathepsin-B cleavable exatecan topoisomerase-1 inhibitor payloads covalently bound to short polyethylene glycol chains surrounding a silica core, the C’Dot. ELU001 binds to cancer cells expressing FRα and is internalized into the lysosome where it releases the exatecan payload. ELU001’s dose escalation study reported at ESMO Congress 2023 (1), examined weekly, bi-weekly (Q2W), and tri-weekly schedules over a range of doses in 42 patients. The study revealed that ELU001 could be administered safely and identified a dose level and schedule for the Expansion Studies described below. 22 of the patients with ovarian or endometrial cancers had >1 post-baseline scan(s), of these 2 had a PR and 19 had SD by RECIST v1.1 criteria. ELU001 demonstrated activity against tumors across a range of FRα expression levels, from low to high, retrospectively assessed using the VENTANA FOLR1 RxDx assay and the PS2+ scoring system. Methods: The current multicenter, Tumor Group Expansion open-label phase 1/2 clinical trial investigates ELU001 in patients with ovarian and endometrial cancers and is enrolling three cohorts; 1) ovarian cancer with high FRα expression, 2) ovarian cancer with moderate and low expression and 3) endometrial cancer with low to high expression with assessments based upon the PS2+ scoring system (high = ≥ 75%, moderate = ≥ 50% to < 75%, low = 25% to < 50%, negative = <25% of tumor cells with 2+ or 3+ staining intensity). An initial exploratory dose of 2.0 mg/m 2 Q2W was employed in all three cohorts and a second dose of 1.7 mg/m 2 Q2W will be studied in the ovarian cancer cohorts. Patients will ultimately be randomized to one of two or more doses to optimize dosing for registration. Primary endpoint: Objective Response Rate (ORR); secondary endpoints include DOR, PFS, TFST, PFS2, OS, adverse events, PK, and ADA assessments. Approximately 20 patients per tumor group will be recruited in the U.S. 1. Ann. Oncol. (2023) 34 (suppl_2): S458-S497. Clinical trial information: NCT05001282.