Summary

This is a first-in-human open-label Phase 1/2a study to evaluate the safety, tolerability,
pharmacokinetics, pharmacodynamics, and preliminary clinical activity of 23ME-00610 given by
intravenous infusion in patients with advanced solid malignancies who have progressed on all
available standard therapies

Objectives

This study includes a dose-escalation phase in Part A to determine the maximum tolerated dose
(MTD) and/or recommended phase 2 dose (RP2D) followed by 6 monotherapy expansion arms in Part
B to further evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and
clinical activity of 23ME-00610 in patients with solid malignancies.

5 tumor- specific monotherapy expansion cohort will enroll up to 15 patients/cohort with the
following locally advanced (unresectable) or metastatic solid malignancies:

1. Clear cell renal cell carcinoma (ccRCC)

2. Epithelial ovarian, fallopian tube or primary peritoneal carcinoma

3. Neuroendocrine cancers

4. Microsatellite instability-high (MSI-H) and/or tumor mutational burden-high (TMB-H)
solid cancers and

5. Extensive stage Small cell lung cancer (ES-SCLC)

A cohort of up to 8 evaluable adolescent patients with locally advanced (unresectable), or
metastatic solid cancers will also be enrolled.

Approximately 15 additional evaluable patients will be added to the cohorts with Epithelial
ovarian, fallopian tube or primary peritoneal carcinoma and Neuroendocrine cancers in Part B
to evaluate another dose level with pharmacologic or PD evidence of therapeutic effect below
the MTD/RP2D identified in Part A (for a maximum of 30 patients in total at the alternate
dose).

Eligibility

1. Part A: Adults = 18 years of age; Part B: = 12 to years of age, weighing at least 40 kg (total body weight)
2. Part A: Histologically-diagnosed locally advanced (unresectable), or metastatic solid cancer that has progressed after all available standard therapy for the specific tumor type, or for which all available standard therapy has proven to be ineffective or if no further standard therapy exists. Part B:
3. Cohort 1B: Histologically-diagnosed locally advanced (unresectable) or metastatic ccRCC that has progressed following all available standard therapy (e.g., anti-PD(L)-1, anti-vascular endothelial growth factor [VEGF] kinase inhibitors), or if no further standard therapy exists.
4. Cohort 2B: Histologically-diagnosed locally advanced (unresectable) or metastatic, platinum-resistant epithelial ovarian, fallopian tube or primary peritoneal carcinoma (i.e., disease recurrence within 6 months of completion of platinum-based therapy) that has progressed following all available standard therapy, or if no further standard therapy exists.
5. Cohort 3B: The following histologically-diagnosed locally advanced (unresectable) or metastatic neuroendocrine cancers that have progressed following all available standard therapy, or if no further standard therapy exists:
6. Merkel cell carcinoma
7. Well-differentiated Grade 3 neuroendocrine cancers with unfavorable biology (as per National Comprehensive Cancer Network [NCCN] guidelines) from any site
8. Poorly differentiated neuroendocrine carcinoma (or extrapulmonary large and small cell carcinoma)
9. Patients with other cancers that show evidence of focal neuroendocrine differentiation may be included with approval from the medical monitor at 23andMe.
10. Cohort 4B: Histologically-diagnosed locally advanced (unresectable) or metastatic solid cancer that has progressed following all available standard therapy, or if no further standard therapy exists and meets the following criteria: TMB-H solid cancer that has been confirmed by the FoundationOne CDx assay or other industry/institutional equivalent platform forTMB assessment using a cutoff of greater than or equal to 10 mutations/megabase and/or MSI-H solid cancer that has been confirmed by immunohistochemistry for MMR proteins or polymerase chain reaction (PCR) of microsatellites or MMR gene mutation by a next-generation sequencing (NGS) panel.
11. Cohort 5B: In jurisdictions where local regulations and IRB/EC allows, adolescents with histologically-diagnosed locally advanced (unresectable), or metastatic solid cancer that has progressed after all available standard therapies for the specific tumor type, or if no further standard therapy exists.
12. Cohort 6B: Histologically-diagnosed locally advanced (unresectable) or metastatic ES-SCLC that has progressed following all available standard therapy, or if no further standard therapy exists.
13. Part A: Adults 18+: Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1; Part B: Adolescents = 12 to < 16 years of age: Lansky Play Scale = 50; Adolescents = 16 years of age: Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1;
14. Life expectancy = 12 weeks
15. Part A: Patients without RECIST measurable disease (e.g., evaluable disease only) will be eligible for enrollment in Part A, regardless of tumor type; Part B: Patients enrolled in Part B must have measurable disease by per RECIST 1.1 and have = 1 site of measurable disease that has not been previously irradiated.

Treatment Sites in Georgia