Safety, efficacy, and PKPD of 23ME-00610, a first-in-class anti-CD200R1 antibody, in patients with advanced or metastatic ovarian cancer: Results from a multi-center multi-country phase 1/2a expansion cohort.
Authors: Ali Raza Khaki, Albiruni Ryan Abdul Razak, Scott A. Laurie, Ching-Chang Hwang, Anh N. Diep, Maike Schmidt, Roo Vold, Sophia Majeed, Dylan M. Glatt, Julie Krystal
Journal: Journal of Clinical Oncology (2024)

5575 Background: 23ME-00610 is being evaluated in a Phase 1/2a clinical trial in patients with advanced solid malignancies (NCT05199272) and has demonstrated an acceptable safety and tolerability profile, with favorable PK and peripheral CD200R1 saturation. Here, we report data from the ovarian cancer Phase 2a expansion cohort for the first time. Methods: Eligible patients had histologically diagnosed locally advanced (unresectable) or metastatic platinum-resistant epithelial ovarian, fallopian tube, or peritoneal carcinoma who have progressed on standard therapies. Key exclusion criteria included active autoimmune disease requiring immunosuppressive therapy, and Grade ≥ 3 immune-mediated toxicity related to prior immunotherapy that led to discontinuation. The primary objective was evaluation of clinical antitumor activity. Exploratory biomarkers included CD200R1 and CD200 tumor expression by IHC in archival tissue, germline genotyping, and polygenic risk score calculation for immune-mediated and cancer-susceptibility phenotypes. At least 15 patients were accrued to characterize target-specific biomarkers and efficacy. Patients received 1400 mg given IV every 3 weeks until disease progression, and CT/MRI scans were conducted every ~ 8 weeks. Results: Between March 27 and October 23, 2023, 15 patients with advanced ovarian cancer (86.7% stage IV, age: 34 to 76), who received a median of 4 prior treatment lines (range: 1 to 12), were enrolled and received ≥ 1 dose of 23ME-00610. Median exposure was 29 days (range: 1 – 126 days), and 12 patients (80%) had disease progression by the December 13, 2023 data cutoff. In the 14 efficacy evaluable patients, investigator assessed stable disease rate was 7.1% (N=1) and median progression free survival (mPFS) was 1.5 months (median potential follow-up time was 4.3 mo). At least 1 treatment emergent adverse event (TEAE) was reported by all patients (N=15). Related TEAEs occurred in 7 patients (46.7%); most were G1 (13.3%) and G2 (26.7%), and the most common were maculopapular rash (13.3%) and pruritus (13.3%). Immune related TEAEs were G1 (13.3%) and G2 (13.3%) and included pruritus (13.3%), rash and hypothyroidism (6.7% each). 15 serious adverse events (TESAEs) that are commonly seen for ovarian cancer were reported in 5 patients (33.3%), including G3 deep vein thrombosis and G4 pneumonia (6.7% each). No G5 or TEAEs leading to 23ME-00610 discontinuation were reported. 1400 mg dose resulted in full peripheral target engagement and minimal treatment-emergent ADA. Conclusions: 23ME-00610 continues to show encouraging PKPD and acceptable safety, but only modest disease control in unselected advanced ovarian cancer patients. Phase 2a expansion trials of 23ME-00610 utilizing retrospective biomarker analyses are ongoing in multiple indications. Clinical trial information: NCT05199272 .