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.
Bibliographic record
Abstract
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 .
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".