A Phase 1/2a, Multicenter, Open-Label, Dose-Escalation and Expansion Study of Intravenously Administered 23ME-00610 in Patients With Advanced Solid Malignancies
Overview
- Phase
- Phase 1
- Intervention
- 23ME-00610
- Conditions
- Solid Tumor
- Sponsor
- 23andMe, Inc.
- Enrollment
- 141
- Locations
- 13
- Primary Endpoint
- Part A: Incidence and severity of dose-limiting toxicities (DLTs)
- Status
- Active, not recruiting
- Last Updated
- last year
Overview
Brief 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
Detailed Description
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).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Part A: Adults ≥ 18 years of age; Part B: ≥ 12 to years of age, weighing at least 40 kg (total body weight)
- •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.
- •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.
- •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.
- •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:
- •Merkel cell carcinoma
- •Well-differentiated Grade 3 neuroendocrine cancers with unfavorable biology (as per National Comprehensive Cancer Network \[NCCN\] guidelines) from any site
- •Poorly differentiated neuroendocrine carcinoma (or extrapulmonary large and small cell carcinoma)
- •Patients with other cancers that show evidence of focal neuroendocrine differentiation may be included with approval from the medical monitor at 23andMe.
- •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:
Exclusion Criteria
- •Females who are pregnant (positive serum pregnancy test within 7 days prior to study drug administration) or breastfeeding.
- •Immune Related Medical History:
- •Active autoimmune disease that has required systemic disease-modifying or immunosuppressive treatment within the last 2 years
- •Receipt of systemic immunosuppressive therapy (e.g. steroids) within 4 weeks prior to the start of study drug administration
- •History of idiopathic pulmonary fibrosis, interstitial lung disease, organizing pneumonia, non-infectious pneumonia that required steroids, or evidence of active, non-infectious pneumonitis
- •History of Grade ≥ 3 immune-mediated toxicity
- •Prior allogeneic or autologous bone marrow transplant, or other solid organ transplant.
- •History of a positive test for:
- •Hepatitis C virus (HCV) infection, except for those who have completed curative therapy for HCV and have undetectable HCV RNA
- •Hepatitis B virus (HBV) infection, except for those who are receiving treatment with HBV-active nucleos(t)ide antiviral therapy at the time of study entry and have undetectable HBV DNA
Arms & Interventions
Part A
Patients will receive escalating doses of 23ME-00610
Intervention: 23ME-00610
Part B
Patients will receive the recommended dose(s) of 23ME-00610
Intervention: 23ME-00610
Outcomes
Primary Outcomes
Part A: Incidence and severity of dose-limiting toxicities (DLTs)
Time Frame: 21 days
Part B adolescents: Incidence and severity of dose-limiting toxicities (DLTs)
Time Frame: 21 days
Part A: Incidence and severity of adverse events (AEs)
Time Frame: Up to 90 days post treatment
Part B adolescents: Incidence and severity of adverse events (AEs)
Time Frame: Up to 90 days post treatment
Part A: Incidence and severity of serious adverse events (SAEs)
Time Frame: Up to 90 days post treatment
Part B adolescents: Incidence and severity of serious adverse events (SAEs)
Time Frame: Up to 90 days post treatment
Secondary Outcomes
- Part A: Prevalence and incidence of antidrug antibodies (ADA) to 23ME-00610(Up to 5 days post treatment discontinuation)
- Overall survival (OS)(Up to 5 years)