Efficacy, safety and PKPD of 23ME-00610, a first-in-class anti-CD200R1 antibody, in patients with advanced or metastatic clear-cell renal cell carcinoma (ccRCC): Results from a multi-center multi-country phase I/IIa 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 ccRCC Phase 2a expansion cohort for the first time.MethodsPatients had histologically-diagnosed locally advanced or metastatic ccRCC with progression on standard therapy. 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 5 and December 12, 2023, 9 patients, median age 61 years (range 43-75), with advanced ccRCC were enrolled. All patients progressed on prior PD-1/L1 and anti-VEGF/kinase inhibitors and received a median of 4 prior treatment lines (range 2-7). Patients received a median of 3 cycles (range 2-8) of 23ME-00610, with 3 patients remaining on study by the April 1, 2024 data cutoff. Related treatment-emergent AEs (TEAEs) occurred in 3 patients (33.3%); all were G1/G2, were reported once each (N=1, 11.1%), and included dry mouth, nausea, constipation, and vomiting. No immune related TEAEs, G4/G5 AEs, or TEAEs leading to 23ME- 00610 dose interruption or discontinuation were reported. In the 9 efficacy evaluable patients, one (11.1%) CD200-positive patient had sustained tumor shrinkage in multiple lesions. 1400 mg resulted in full peripheral saturation of CD200R1.Conclusions23ME-00610 shows anti-tumor activity in immunotherapy-refractory ccRCC and continues to show an acceptable safety and tolerability profile, full peripheral target engagement, and PK that supports Q3W dosing. References: 1. Rasco, et al., SITC 2023; 2. Glatt, et al., SITC 2023.Clinical trial identificationNCT05199272.Legal entity responsible for the study23andMe, Inc.Funding23andMe, Inc.DisclosureJ. Krystal: Financial Interests, Personal, Advisory Board: DayOne Bio. A.R. Khaki: Financial Interests, Institutional, Local PI: 23andMe, Janssen, Acrivon Therapeutics; Non-Financial Interests, Advisory Role, Consulting/advisory, declined compensation: Janssen. A.I. Spira: Financial Interests, Personal, Other, Consulting or Advisory Role: Incyte, Mirati Therapeutics, Gritstone Oncology, Jazz Pharmaceuticals, Janssen Research & Development, Mersana, Gritstone Bio, Daiichi Sankyo/AstraZeneca, Array Biopharma, Blueprint Medicines, Regeneron, Lilly, Black Diamond Therapeutics, Sanofi; Financial Interests, Personal, Other, Consulting or Advisory Role / Honoraria: Amgen, Novartis, Takeda, AstraZeneca/MedImmune, Merck, Bristol Myers Squibb; Financial Interests, Personal, Other, Honoraria: CytomX Therapeutics, Janssen Oncology, Bayer; Financial Interests, Institutional, Officer, CEO: Next Oncology Virginia; Financial Interests, Personal, Stocks/Shares: Eli Lilly; Financial Interests, Institutional, Local PI: LAM Therapeutics, Roche, AstraZeneca, Boehringer Ingelheim, Astellas Pharma, MedImmune, Novartis, Newlink Genetics, Incyte, Abbvie, Ignyta, Trovagene, Takeda, Macrogenics, CytomX Therapeutics, Astex Pharmaceuticals, Bristol Myers Squibb, Loxo, Arch Therapeutics, Gritstone, Plexxikon, Amgen, Daiichi Sankyo, ADCT, Janssen Oncology, Mirati Therapeutics, Rubius, Synthekine, Mersana, Blueprint Medicines, Kezar, Revolution Med, Regeneron, Loxo, Alkermes, Medikine, Black Diamond Therapeutics, Nalo Therapeutics, Scorpion Therapeutics, Arrivent Biopharma. 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 Ingleheim, 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 Ingleheim, Medison, Inhibrx. D. Maslyar, C.C. Hwang, R. Vold: Financial Interests, Institutional, Full or part-time Employment: 23andMe. D.M. Glatt, A.N. Diep, M. Schmidt: Financial Interests, Institutional, Full or part-time Employment: 23andMe; Financial Interests, Institutional, Stocks/Shares: 23andMe.