Safety, efficacy, and PKPD of 23ME-00610, a first-in-class anti-CD200R1 antibody, in patients with advanced neuroendocrine cancers: Results from a multi-center multi-country phase 1/2a expansion cohort.

4129 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 neuroendocrine cancer Phase 2a expansion cohort for the first time. Methods: Eligible patients had histologically diagnosed locally advanced (unresectable) or metastatic neuroendocrine cancers who had 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 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 February 23 and November 7, 2023, 16 patients with advanced neuroendocrine neoplasms (87.5% Stage IV; 62.5% NEC, 25% pancreatic, 6.3% colorectal; age: 33 to 74), who received a median of 3.5 prior treatment lines (range: 1 to 10), were enrolled and received ≥ 1 dose of 23ME-00610. Median exposure was 43.5 days (range: 1 – 212 days), and 11 patients (69%) had disease progression by the December 13, 2023 data cutoff. In the 15 efficacy evaluable patients, investigator assessed stable disease rate was 46.7% (N=7) and median progression free survival (mPFS) was 2.1 months (median potential follow-up time was 6.3 mo); 4 patients (26.7%) had durable SD > 6 mo. At least 1 treatment emergent adverse event (TEAE) was reported by all patients (N=16). Related TEAEs occurred in 8 patients (50%); all were G1/G2, and the most common were maculopapular rash (18.8%), pruritus (18.8%), nausea (12.5%), and fatigue (12.5%). Immune related TEAEs were G1 (18.8%) and included maculopapular rash (18.8%) and pruritus (12.5%). No G4/G5 or TEAEs leading to 23ME-00610 discontinuation were reported. 1400 mg dose resulted in full peripheral saturation of CD200R1 and minimal treatment-emergent ADA. Conclusions: 23ME-00610 continues to show encouraging PKPD, safety, and disease control in a subset of unselected patients with advanced neuroendocrine cancers. Exploratory biomarker data warrant additional analyses to examine the potential for biomarker stratification on disease outcomes. Phase 2a expansion trials of 23ME-00610 utilizing retrospective biomarker analysis are ongoing in multiple indications. Clinical trial information: NCT05199272 .