Efficacy, safety and PKPD of 23ME-00610, a first-in-class anti-CD200R1 antibody, in patients with tumor mutational burden-high (TMB-H) and/or microsatellite instability-high (MSI-H) cancers: Results from an expansion cohort

Background23ME-00610, an anti-CD200R1 antibody, is being evaluated in a Phase 1/2a clinical trial in patients with advanced solid malignancies (NCT05199272) and has demonstrated acceptable safety and tolerability, with favorable PK and peripheral CD200R1 saturation, and anti-tumor activity [1,2]. Here, we report data from the TMB/MSI-H Phase 2a expansion cohort for the first time.MethodsPatients had histologically-diagnosed locally advanced or metastatic TMB/MSI-H solid cancers, including patients with TMB ≥ 10 and ≥ 20 mutations/mb. Patients received 1400 mg given IV every 3 weeks until disease progression, unacceptable toxicity, or withdrawal from study. Exploratory biomarkers included CD200/R1 tumor expression, host genotyping, and peripheral target engagement. Adverse events (AEs) were assessed using CTCAE v5. Disease assessments were conducted every 8 weeks, and response was assessed by investigators using RECIST 1.1 criteria.ResultsBetween June 20, 2023 and February 28, 2024, 12 patients, median age 58.5 years (range 36-79), with locally advanced or metastatic TMB-H (N=8; 66.7%) and/or MSI-H (N=4; 33.3%) solid cancers who received a median of 5 prior treatments (range 3-11; prior immunotherapy in 75%) were enrolled. Patients received a median of 3 cycles of 23ME-00610 (range 1-7), with 4 patients remaining on study by the April 1, 2024 data cutoff. Related non-serious AEs occurred in 7 patients (58.3%), including 2 patients (16.7%) with G3 anaemia (N=1) and G3 lymphocyte decrease (N=1). One incident of non-related G2 dyspnea led to dose interruption. No study drug related AEs/immune related AEs (irAEs) ≥ G3, or events leading to 23ME-00610 discontinuation, were reported. In the 10 efficacy evaluable patients, stable disease rate was 40%. 1400 mg resulted in full peripheral saturation of CD200R1.Conclusions23ME-00610 continues to show acceptable safety and tolerability, full peripheral target engagement, and PK that supports Q3W dosing, though limited anti-tumor activity as monotherapy in a small cohort of participants with TMB-H/MSI-H tumors. 1. Rasco, et al. SITC 2023 2. Glatt, et al. SITC 2023.Clinical trial identificationNCT05199272.Legal entity responsible for the study23andMe, Inc.Funding23andMe, Inc.DisclosureA. Naing: Financial Interests, Personal, Advisory Board: CTI, Deka Biosciences, Janssen Biotech, NGM Bio, PsiOxus Therapeutics, Immune-Onc Therapeutics, STCube Pharmaceuticals, OncoSec Keynote 695, Genome & Company, CytomX Therapeutics, Nouscom, Merck Sharp & Dohme Crop, Servier, Lynx Health, AbbVie, PsiOxus; Financial Interests, Institutional, Invited Speaker: AKH Inc., ASCO Direct Oncology Highlights, European Society for Medical Oncology; Financial Interests, Personal, Invited Speaker: Lynx Group, Society for Immunotherapy of Cancer, Korean Society of Medical Oncology, Scripps Cancer Care Symposium, CME Outfitters; Financial Interests, Institutional, Coordinating PI: NCI, EMD Serono; Financial Interests, Personal, Local PI: MedImmune, Healios Onc. Nutrition, Atterocor/Millendo; Financial Interests, Institutional, Local PI: Amplimmune, ARMO BioSciences, Karyopharm Therapeutics, Incyte, Novartis, Regeneron, Merck, Bristol Myers Squibb, Pfizer, CytomX Therapeutics, Neon Therapeutics, Calithera Biosciences, TopAlliance Biosciences, Eli Lilly, Kymab PsiOxus, Arcus Biosciences, NeoImmuneTech, Immune-Onc Therapeutics, Surface Oncology, Monopteros Therapeutics, BioNTech Se, Seven & Eight Biopharma, SOTIO Biotech AG; Other, Travel and Accommodation: ARMO BioSciences, NeoImmune Tech, NGM BioPharmaceuticals. A.R. Khaki: Financial Interests, Institutional, Local PI: 23andMe, Janssen, Acrivon Therapeutics; Non-Financial Interests, Advisory Role, Consulting/advisory, declined compensation: Janssen. S. Kummar: Financial Interests, Personal, Advisory Board: Bayer, Gilead, Mundibiopharma, Springworks Theraepeutics, HarbourBiomed, Oxford BioTherapeutics, BPGbio Therapeutics, XYOne Therapeutics, GI Innovation Inc.; Financial Interests, Personal, Advisory Board, Spouse: Cadila Pharmaceuticals; Financial Interests, Personal, Other, Chair, DSMC: Mirati; Financial Interests, Personal, Advisory Board, Consultant: Genome Insight; Financial Interests, Personal, Ownership Interest: Pahtomiq; Financial Interests, Personal, Ownership Interest, Spouse (co-founder): Arexeon; Financial Interests, Personal, Stocks/Shares: Fortress Biotech; Financial Interests, Personal, Other, co-founder: Pathomiq; Financial Interests, Institutional, Local PI, Trial funding: ADC Therapeutics, Pionyr Therapeutics, Eisai, Bristol Myers Squibb, Syndax, SeaGen, ORIC, EMD Serono, Genome & Company, Moderna, Amgen, ASTX Therapeutics, PMV Pharmaceuticals, Elevation Oncology, Gilead, Day One BioPharmaceuticals, Sillajen Inc.; Financial Interests, Institutional, Local PI, trial funding: 23&Me; Financial Interests, Institutional, Local PI, Trial Funding: Deciphera Pharmaceuticals Llc, AstraZeneca, Immunitas Therapeutics, Inc., Mirati Therapeutics Inc, Transcenta Therapeutics, Inc., Adanate, Inc, GV20 Therapeutics Llc, Blueprint Medicines Corp, Nuvectis Pharma, Inc., Fog Pharmaceuticals. M.N. Al-Hallak: Financial Interests, Personal, Invited Speaker: Ipsen, AstraZeneca, Guardant Health, Takeda, Seagen; Financial Interests, Research Grant: Purple Biotech, U CAN-CER VIVE Foundation; Financial Interests, Local PI: Purple Biotech, Amgen, Incyte Corporation, Merus, Mirror Biologics, Tvardi, Astellas, Roche, 23andMe, Inc, NuCana, Refmal; Financial Interests, Personal, Local PI, Invited Speaker: AstraZeneca. A.R. Abdul Razak: Financial Interests, Personal, Invited Speaker: Medison; Financial Interests, Institutional, Local PI: 23&Me, Abbisko, AbbVie, Adaptimmune, Amgen, AstraZeneca, Bayer, Biontech, Blueprint Medicine, Boehringer Ingelheim, Bristol Myers Squibb, Cogent Biosciences, Daiichi Sankyo, Deciphera, Frontier Biopharma, Gilead, GSK, Iterion Therapeutics, Karyopharm Therapeutics, MedImmune, Medison, Merck, Neoleukin, Novartis, Pfizer, Polaris, Roche/Genentech, Rain Therapeutics and Symphogen.; Non-Financial Interests, Advisory Role: Boehringer Ingelheim, Medison, Inhibrx. A.N. Diep: Financial Interests, Institutional, Full or part-time Employment: 23andMe, Inc.; Financial Interests, Institutional, Stocks/Shares: 23andMe, Inc. M. Schmidt: Financial Interests, Institutional, Full or part-time Employment: 23andMe; Financial Interests, Institutional, Stocks/Shares: 23andMe. D. Maslyar, R. Vold, C.C. Hwang: Financial Interests, Institutional, Full or part-time Employment: 23andMe. D.M. Glatt: Financial Interests, Institutional, Full or part-time Employment: 23andMe; Financial Interests, Institutional, Stocks/Shares: 23andMe.