Abstract LB299: Clinical pharmacokinetics and peripheral receptor occupancy of OR502, best-in-class antibody against leukocyte immunoglobulin-like receptor B2 (LILRB2), alone and in combination with cemiplimab

Abstract Background: Based on its single-agent clinical activity and excellent safety profile, OR502 has best-in-class properties. Preclinically, OR502 reverses and prevents myeloid cell-mediated immune suppression and restores T cell functions with superior activity than other antibodies targeting LILRB2. OR502 binds to a distinct epitope of LILRB2, and blocks more broadly LILRB2 binding to its ligands. In addition, OR502 co-engages activating FcγR on myeloid cells. Here we report pharmacokinetic (PK) and receptor occupancy (RO) data from a phase 1 study [NCT06090266] dose escalation cohorts in patients with refractory solid tumors. Methods: Primary objectives included selection of an OR502 dose for the next stage of study, supported by LILRB2 RO and PK in addition to safety and efficacy. OR502 was given IV in 21-day (D) cycles (C) in 5 cohorts from 100-1600 mg in 2 separate escalations: monotherapy (mono) or + standard dosing of cemiplimab (combo). Serial PK sampling was performed during C1 and C3, then D1 every other C. Peripheral RO was assessed weekly during C1 and C3 and on D1 of C2 and C4 by flow cytometry. An OR502 anti-idiotype was used to measure OR502 bound to LILRB2 on the surface of myeloid cells vs unoccupied and total LILRB2 before and after OR502 administration. PK data were analyzed using PKanalix®. Results: Table summarizes patient characteristics, PK and RO from mono and combo escalation cohorts. Conclusions: OR502 PK and RO support Q3W dosing, and based on near-complete RO and predictable PK, justify the OR502 dose selected for mono and combo expansion cohorts of 800 mg IV Q3W in PD-(L)1 pretreated cutaneous melanoma and NSCLC, respectively. Citation Format: Andrae Vandross, David Sommerhalder, Mohamad Salkeni, Damien Cronier, Myriam N. Bouchlaka, Kamal Puri, Nenad Sarapa, Lesley Skingley, Mike Yefimenko, Alice Bexon, Shiraj Sen. Clinical pharmacokinetics and peripheral receptor occupancy of OR502, best-in-class antibody against leukocyte immunoglobulin-like receptor B2 (LILRB2), alone and in combination with cemiplimab [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr LB299.