Abstract CT174: First-in-class anti-CD200R1 antibody 23ME-00610 in patients with advanced solid malignancies: Phase 1 results

Background: CD200R1 was identified as a promising immuno-oncology (IO) target from the 23andMe database. Pleiotropic causal variants with opposing effect on risks for cancer and immune diseases, referred to as an IO signature, were observed in 3 components of the CD200R1 pathway. 23ME-00610 is a first-in-class monoclonal antibody that potently inhibits the CD200R1 immune checkpoint (KD less than 0.1 nM). The dose escalation portion of the first-in-human, Phase 1/2a study of 23ME-00610 (NCT05199272) has been completed and we are reporting data for the first time. Methods: Eligible patients were alteast 18 years with histologically diagnosed locally advanced (unresectable), or metastatic carcinoma or sarcoma who have progressed on standard therapies with ECOG 0 or 1. Key exclusion criteria included active autoimmune disease requiring immunosuppressive therapy and Grade 3 or above immune-mediated toxicity related to prior immunotherapy that led to discontinuation. Dose escalation consisted of accelerated titration (2 and 6 mg) followed by a 3+3 design (20, 60, 200, 600 and 1400 mg). Up to 12 participants were included in a PKPD backfill cohort at the recommended phase 2 dose (RP2D) or a previously evaluated dose level. Participants received 23ME-00610 intravenously every 3 weeks (Q3W) infused over 30 minutes. The primary objectives of Phase 1 were determination of the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D), safety and tolerability. Key secondary and exploratory objectives included pharmacokinetics (PK), pharmacodynamics (PD) and antitumor activity of 23ME-00610. Results: Between January 5th, 2022 and November 28, 2022, 21 participants (11/10 male/female; age range: 21-80 years) were enrolled and received ≥ 1 dose of 23ME-00610 across the 2 to 1400 mg cohorts (median duration of exposure: 50 days; range:1-231 days). No dose limiting toxicities, treatment related serious adverse events (TRSAEs) or AEs leading to discontinuation were observed. 14/21 (67%) participants experienced atleast 1 TRAE; the majority were Grade 1 or 2. The most commonly reported TRAEs occurring in atleast 2 participants across all dose levels were headache, fatigue, nausea and pruritis. There was 1 Grade 3 TRAE of increased blood creatinine phosphokinase. Investigator-assessed immune-related AEs including hypothyroidism, pruritis, fatigue and chills were observed at doses 60 mg and above. The PK of 23ME-00610 were dose-proportional at doses 60 mg and above, with a median terminal half-life of ~12 days at 1400 mg. Peripheral saturation of CD200R1 was observed at doses 60 mg and above, as measured by receptor occupancy on T cells and neutrophils, and levels of free soluble CD200R1. Analysis of additional PD data, including cytokines, is ongoing. Conclusion: 23ME-00610 demonstrated an acceptable safety and tolerability profile, with favorable PK and peripheral CD200R1 saturation. Increased immune-related AEs were observed at higher, pharmacologically relevant dose levels. Based on Phase 1 data, 1400 mg 23ME-00610 Q3W will be evaluated in Phase 2a. Citation Format: Shivaani Kummar, Albiruni ABDUL RAZAK, Scott Laurie, Sariah Kell, Dylan Glatt, Sophia R. Majeed, Drew Rasco. First-in-class anti-CD200R1 antibody 23ME-00610 in patients with advanced solid malignancies: Phase 1 results [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT174.