150P - Phase I/IIa trial of CD200R1 inhibitor 23ME-00610: Exploratory analyses of tissue-based and genetic biomarkers

Background

23ME-00610 is being evaluated in a phase 1/2a clinical trial in patients with advanced solid cancers (NCT05199272) and has demonstrated acceptable safety and tolerability and anti-tumor activity (Rasco et al., 2023). For the first time, we summarize the exploratory tissue-based biomarker data and genetic analysis.

Methods

FFPE tumor tissues were assessed by IHC and RNASeq for CD200R1, CD200, and immune contexture at baseline and following 23ME-00610 treatment. Membrane associated CD200 was quantified as an H-score assessing both intensity and percentage of positive cells (range 0 and 300). 23andMe Research Cohort (Tung et al., 2011) data was used to construct polygenic risk scores (PRSs) for immune- and oncology-associated traits and applied to trial participants genotyped on the same 23andMe platform.

Results

116 patients were enrolled: dose escalation (28 participants) and 5 disease specific expansion cohorts: renal (10), ovarian (27), neuroendocrine (24), MSI/TMB-H (13), and small cell lung (14). 13 of 14 patients with clinical benefit (CB), defined as 6-month PFS and/or tumor shrinkage at time of data cutoff, had evaluable tissue for IHC. Median H-score for patients with CB was 45 (IQR 145.5), compared to 2.5 (IQR 52.2) for patients with progressive disease (n = 66 evaluable tumors). Pre-treatment tumors from patients with CB had lower levels of activated T/NK by IHC and RNA, potentially indicating a more immune suppressive environment. IHC and RNASeq data showed lower CD68+/CD163+ cells and increased expression of IFNγ post- treatment. Higher germline genetic risk for a subset of immune-mediated phenotypes trended with the development of some immune-related AEs (irAEs) in a subset of patients.

Conclusions

Higher tumor expression of CD200 correlated with CB in some patients treated with 23ME-00610, warranting further exploration of this biomarker for potential future patient selection. Early data suggests that 23ME-00610 may reverse the immunosuppressive state of CD200+ tumor microenvironment. Ongoing genetic analyses will evaluate if immune-mediated phenotypes may be associated with increased risk to develop irAEs as has been demonstrated in other studies (Khan et al., 2019 and 2021).

Clinical trial identification

NCT05199272.

Editorial acknowledgement

Legal entity responsible for the study

23andMe, Inc.

Funding

23andMe, Inc.

Disclosure

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. 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, GV20; 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; Other, Travel and accommodation: NGM Biopharmaceuticals. A.N. Diep: Financial Interests, Institutional, Full or part-time Employment: 23andMe, Inc.; Financial Interests, Institutional, Stocks/Shares: 23andMe, Inc.. C.C. Hwang: Financial Interests, Institutional, Full or part-time Employment: 23andMe. A.C. Reisetter, C. Hom, D.M. Glatt, M. Schmidt: Financial Interests, Institutional, Full or part-time Employment: 23andMe; Financial Interests, Institutional, Stocks/Shares: 23andMe. Z.L. Fuller: Financial Interests, Institutional, Full or part-time Employment: 23andMe; Financial Interests, Institutional, Stocks or ownership: 23andMe.