Solid Tumor
Conditions
Keywords
Cancer, Phase 1, Solid Tumor, Oncology, NK, ULBP6, Immunotherapy
Brief summary
This is a first-in-human open-label study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary clinical activity of 23ME-01473 given by intravenous infusion in participants with advanced solid cancers who have progressed or are intolerant of available standard therapies.
Detailed description
This study includes a dose escalation portion to determine the maximum tolerated dose (MTD) and/or the recommended phase 2 dose (RP2D) to evaluate the clinical activity of 23ME-01473 and further evaluate its safety, tolerability, pharmacokinetics, and pharmacodynamics in participants with solid malignancies.
Interventions
DRUG23ME-01473
23Me-01473 given by intravenous infusion
Sponsors
23andMe, Inc.
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 110 Years
Healthy volunteers
No
Inclusion criteria
1. Phase 1: Adults ≥ 18 years of age 2. Phase 1: Histologically-diagnosed locally advanced (unresectable), or metastatic carcinoma or sarcoma that has progressed after standard therapy for the specific tumor type. 3. Adults 18+: Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 4. Life expectancy ≥ 12 weeks 5. Phase 1: Participants with evaluable disease are eligible regardless of tumor type, RECIST 1.1 can be used to assess disease progression.
Exclusion criteria
1. Females who are pregnant (positive serum pregnancy test within 7 days prior to study drug administration) or breastfeeding. 2. Immune-Related Medical History 1. Active autoimmune disease that has required systemic disease-modifying or immunosuppressive treatment within the last 2 years 2. Receipt of systemic immunosuppressive therapy (e.g. steroids) within 4 weeks prior to the start of study drug administration 3. History of idiopathic pulmonary fibrosis, interstitial lung disease, organizing pneumonia, non-infectious pneumonia that required steroids, or evidence of active, non-infectious pneumonitis 4. History of Grade ≥ 3 immune-mediated toxicity 3. Prior allogeneic or autologous bone marrow transplant, or other solid organ transplant 4. History of a positive test for: 1. Hepatitis C virus (HCV) infection, except for those who have completed curative therapy for HCV and have undetectable HCV RNA 2. 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 3. Human Immunodeficiency Virus (HIV) infection, except those who meet the following criteria: CD4+ T cells ≥ 350 cells/μL, no history of Acquired Immunodeficiency Syndrome (AIDS)-defining opportunistic infections, HIV RNA \< 50 copies/mL, and on a stable antiretroviral regimen for at least 3 months 5. Prior anticancer therapy, including chemotherapy, targeted therapy, biological therapy or immune-checkpoint inhibitors within 4 weeks or 5 drug half-lives (whichever is shorter) 6. History of another malignancy in the previous 2 years, unless cured by surgery alone and continuously disease free. 7. Uncontrolled or symptomatic CNS (central nervous system) metastases and/or carcinomatous meningitis 8. Recent history (within 6 months) of serious cardiovascular disease
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Phase 1:Incidence and severity of dose-limiting toxicities (DLTs) | First dose through 21 days post dose |
| Phase 1: Incidence and severity of adverse events (AEs) | From Screening through 90 days post treatment |
| Phase 1 Incidence and severity of serious adverse events (SAEs) | From Screening through 90 days post treatment |
| ORR based on investigator assessment against RECIST 1.1 criteria | From baseline until disease progression (up to 5 years) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease Control Rate (DCR) | From baseline until disease progression (up to 5 years) | Disease control rate based on investigator assessment against RECIST 1.1 criteria |
| Progression free survival (PFS) | From baseline until disease progression (up to 5 years) | Progression free survival based on investigator assessment against RECIST 1.1 criteria |
| Time of maximum serum concentration (Tmax) following a single dose of 23ME-01473 | [Time Frame: Cycle 1 (21 days, from Cycle 1 Day 1 predose to Cycle 2 Day 1 predose)] | — |
| Area under the concentration-time curve from zero to the last measurable concentration (AUClast) following a single dose of 23ME-01473 | [Time Frame: Cycle 1 (21 days, from Cycle 1 Day 1 predose to Cycle 2 Day 1 predose)] | — |
| Area under the concentration-time curve from zero extrapolated to infinity (AUCinf) following a single dose of 23ME-01473 | [Time Frame: Cycle 1 (21 days, from Cycle 1 Day 1 predose to Cycle 2 Day 1 predose)] | — |
| Last measurable serum concentration (Clast) following a single dose of 23ME-01473 | [Time Frame: Cycle 1 (21 days, from Cycle 1 Day 1 predose to Cycle 2 Day 1 predose)] | — |
| Maximum serum concentration (Cmax) following multiple doses of 23ME-01473 | [Time Frame: Cycle 4 (21 days, from Cycle 4 Day 1 predose to Cycle 5 Day 1 predose)] | — |
| Time of maximum serum concentration (Tmax) following multiple doses of 23ME-01473 | [Time Frame: Cycle 4 (21 days, from Cycle 4 Day 1 predose to Cycle 5 Day 1 predose)] | — |
| Area under the concentration-time curve from time zero to the end of the dosing interval (AUCtau) following multiple doses of 23ME-01473 | [Time Frame: Cycle 4 (21 days, from Cycle 4 Day 1 predose to Cycle 5 Day 1 predose)] | — |
| Serum concentration at the end of the dosing interval (Ctau) following multiple doses of 23ME-01473 | [Time Frame: Cycle 4 (21 days, from Cycle 4 Day 1 predose to Cycle 5 Day 1 predose)] | — |
| Terminal half-life (T1/2) following multiple doses of 23ME-01473 | [Time Frame: Cycle 4 (21 days, from Cycle 4 Day 1 predose to Cycle 5 Day 1 predose)] | — |
| Terminal half-life (T1/2) following a single dose of 23ME-01473 | [Time Frame: Cycle 1 (21 days, from Cycle 1 Day 1 predose to Cycle 2 Day 1 predose] | — |
| Phase 1: Prevalence and incidence of antidrug antibodies (ADA) to 23ME-01473 | From first dose up to 5 days post treatment discontinuation | — |
| Phase 1: Objective response rate (ORR) | From baseline until disease progression (up to 5 years) | ORR based on investigator assessment against RECIST 1.1 criteria |
| Duration of response (DoR) | From baseline until disease progression (up to 5 years) | Duration of response based on investigator assessment against RECIST 1.1 criteria |
Countries
United States
Outcome results
None listed