23andMe Holding Co. announced positive preliminary Phase 2 safety and efficacy data from 23ME-00610, a first-in-class anti-CD200R1 antibody, presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, May 31-June 4. 23andMe presented two posters on 23ME-00610, one each from neuroendocrine and ovarian cancer patient cohorts in its ongoing Phase 1/2a clinical trial. Key takeaways: Confirmed partial response (PR) in patient with well-differentiated pancreatic neuroendocrine cancer (pNET) (> 24 cycles at data cut-off) and qualitative clinical benefit with durable treatment duration (> 12 cycles at data cut-off) and tumor shrinkage in patient with mesonephric adenocarcinoma (a form of ovarian cancer).

23ME-00610 monotherapy demonstrates acceptable safety and tolerability, and achieves the prespecified targets for maximal pharmacology at 1400 mg dosed every three weeks. From archival tumor immunohistochemistry (IHC) analyses, over 70% of patients had detectable tumor cell CD200, and higher expression tended to trend with clinical benefit. In addition to CD200, histology data suggest that immunosuppressed (?cold?) tumors may be more likely to exhibit disease control with 23ME-00610.

Emerging data shows preliminary evidence of clinical benefit from 23ME-00610 treatment associated with lower risk for chronic immune-mediated diseases (e.g., psoriasis, asthma, eczema), yet higher risk for acute immune reactivity and cancer. This aligns with the 23andMe Immuno-oncology Signature, which identifies promising IO targets by pinpointing areas of the genome associated with opposing risk for auto-immune disease and cancer. Further details - neuroendocrine cancers cohort.

Between February 23, 2023 and April 1, 2024, 16 adult patients with advanced neuroendocrine neoplasms who received a median of 3.5 prior treatment lines (range: 1 to 10), were enrolled and received = 1 dose of 23ME-00610. A patient from the Phase 1 portion of the Phase 1/2a trial with well-differentiated pancreatic neuroendocrine cancer (pNET) and high tumor CD200 expression has a confirmed partial response (PR) and remains on treatment (> 21 months). Among the N=16 expansion cohort, the disease control rate was 50% (n=8), and 25.3% of patients were free from clinical progression at 6 months, per RECIST v1.1. The safety and tolerability profile remains acceptable and promising for potential anti-cancer combinations in neuroendocrine patients.

No treatment-emergent adverse events (TEAEs) leading to 23ME-00610 discontinuation were reported. Related treatment-emergent adverse events (TRAEs) 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%). Patients with moderate to high tumor CD200 expression tended to be more likely to derive clinical benefit (PR or durable SD) relative to patients with low or undetectable tumor CD200.

Further details - ovarian cancer cohort: Between March 27, 2023 and April 1, 2024, 16 adult patients with advanced ovarian cancer who received a median of 4 prior treatment lines (range: 1 to 12), were enrolled and received = 1 dose of 23ME-00610. The safety and tolerability profile remains acceptable and promising for potential anti-cancer combinations in ovarian cancer patients. No TRAEs = G4 or AEs leading to 23ME-00610 discontinuation or death were reported.

Related TEAEs occurred in 7 patients (43.8%); most were G1 (12.5%) and G2 (25.0%), and the most common were maculo-papular rash (12.5%) and pruritus (12.5%). Immune-related AEs (irAEs) were = G2 in severity and generally dermatologic and thyroid in nature. A patient with well-differentiated mesonephric adenocarcinoma progressing prior to study enrollment has shown qualitative clinical benefit and durable treatment duration (> 12 cycles), including decreasing CA-125, substantial decreases in malignant ascites, and tumor reduction while on 23ME-00610 treatment.

Additional data from the 23andMe poster presentations at ASCO 2024: Eligible patients had histologically diagnosed locally advanced (unresectable) or metastatic 1) neuroendocrine cancers who had progressed on standard therapies, or 2) metastatic platinum-resistant epithelial ovarian, fallopian tube, or peritoneal carcinoma who have progressed on standard therapies. Exploratory biomarkers included CD200R1 and CD200 tumor expression, germline genotyping, and polygenic risk score calculation for immune-mediated and cancer phenotypes. Patients received 1400 mg given IV every 3 weeks until disease progression, and CT/MRI scans were conducted every ~ 8 weeks.