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Abstract
Background 23ME-00610 is a first-in-class anti-CD200R1 monoclonal antibody in Phase 2 clinical development for advanced solid malignancies that has been shown to rescue T cell function in preclinical studies. CD200R1 was identified as an immuno-oncology target from the 23andMe database, with pleiotropic causal variants that have opposing effect on risks for cancer and immune diseases, referred to as an IO signature, observed in 3 components in this pathway.1 Updated data from the completed dose escalation and PK/PD cohorts in the ongoing Phase 1/2a study of 23ME-00610 is reported.
Methods Eligible participants were atleast 18 years with histologically diagnosed locally advanced or metastatic carcinoma or sarcoma who progressed on standard therapies with ECOG 0–1. Dose escalation consisted of accelerated titration cohorts followed by a 3+3 design and a PK/PD cohort at the highest dose levels. Participants received 23ME-00610 intravenously every 3 weeks (Q3W) until disease progression or unacceptable toxicity. The primary objectives were safety, tolerability and determination of the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D), with the MTD defined by dose limiting toxicities (DLTs) in the first 21 days following cycle 1.
Results Between January 5th, 2022 and the May 15th, 2023 data cut-off date, 28 participants (14/14 male/female; age range: 21–80 years) received atleast 1 dose of 23ME-00610 across 7 dose levels ranging between 2mg to 1400mg (median [range]: 4 cycles [1–15]). There were no DLTs or treatment-related serious adverse events (TRSAEs), and the MTD was not reached. 19/28 (68%) participants experienced atleast 1 TRAE; majority were Grade 1 or 2. All grade TRAEs occurring in atleast 2 participants across all doses were nausea (14%), headache (11%), fatigue (11%), pruritus (11%), rash/maculo-papular rash (11%), arthralgia (11%), hypothyroidism (7%) and cough (7%). There was 1 Grade 3 TRAE of maculo-papular rash that led to treatment discontinuation. Of 27 response evaluable patients, 52% had stable disease with duration ranging from 8 weeks to 40 weeks. Tumor shrinkage was observed in 1 participant with pancreatic neuroendocrine cancer who progressed on standard therapies, with a maximum reduction of 19% in target lesions which remains ongoing at the Week 40 assessment. Preliminary data suggested no evidence of anti-drug antibody emergence following repeated 23ME-00610 administration. Plasma cytokines analyses are ongoing.
Conclusions 23ME-00610 is well-tolerated with a manageable safety profile. The irAEs are consistent with 23ME-00610-mediated immune modulation. The data continue to support evaluation of 1400 mg 23ME-00610 Q3W (RP2D) in the ongoing Phase 2a.
Acknowledgements Dr. Pam Farmer for providing pharmacovigilance support.
Trial Registration NCT05199272
Reference 1. Fenaux J, Fang X, Huang YM, et al. 23ME-00610, a genetically informed, first-in-class antibody targeting CD200R1 to enhance antitumor T cell function. Oncoimmunology. 2023;12(1):2217737.
Ethics Approval The study obtained approval from Advarra IRB (Pro00062976), Salus IRB (START2021.35), MD Anderson OHRP IRB (2021–0888), Oregon Health & Science University IRB (STUDY00023966) and Ontario Cancer Research Ethics Board (3953). All study participants provided informed consent for the study.
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