Clinical trial NCT06290388: Study of 23ME-01473 in Patients With Advanced Solid Malignancies
Official title: A Phase 1/2a, Multicenter, Open-label, Dose Escalation and Expansion Study of Intravenously Administered 23ME-01473 in Participants With Advanced Solid Malignancies
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Solid Tumor
Keywords: Cancer
Phase 1
Solid Tumor
Oncology
NK
ULBP6
Immunotherapy
Lead sponsor: 23andMe, Inc.
Sponsor class: INDUSTRY
First posted: 2024-03-04
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Maximum age (years): 110
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Phase 1:Incidence and severity of dose-limiting toxicities (DLTs)
timeFrame: First dose through 21 days post dose
measure: Phase 1: Incidence and severity of adverse events (AEs)
timeFrame: From Screening through 90 days post treatment
measure: Phase 1 Incidence and severity of serious adverse events (SAEs)
timeFrame: From Screening through 90 days post treatment
measure: ORR based on investigator assessment against RECIST 1.1 criteria
timeFrame: From baseline until disease progression (up to 5 years)
Secondary outcomes:
measure: Phase 1: Prevalence and incidence of antidrug antibodies (ADA) to 23ME-01473
timeFrame: From first dose up to 5 days post treatment discontinuation
measure: Phase 1: Objective response rate (ORR)
timeFrame: From baseline until disease progression (up to 5 years)
measure: Duration of response (DoR)
timeFrame: From baseline until disease progression (up to 5 years)
measure: Disease Control Rate (DCR)
timeFrame: From baseline until disease progression (up to 5 years)
measure: Progression free survival (PFS)
timeFrame: From baseline until disease progression (up to 5 years)
measure: Time of maximum serum concentration (Tmax) following a single dose of 23ME-01473
timeFrame: [Time Frame: Cycle 1 (21 days, from Cycle 1 Day 1 predose to Cycle 2 Day 1 predose)]
measure: Area under the concentration-time curve from zero to the last measurable concentration (AUClast) following a single dose of 23ME-01473
timeFrame: [Time Frame: Cycle 1 (21 days, from Cycle 1 Day 1 predose to Cycle 2 Day 1 predose)]
measure: Last measurable serum concentration (Clast) following a single dose of 23ME-01473
timeFrame: [Time Frame: Cycle 1 (21 days, from Cycle 1 Day 1 predose to Cycle 2 Day 1 predose)]
measure: Area under the concentration-time curve from zero extrapolated to infinity (AUCinf) following a single dose of 23ME-01473
timeFrame: [Time Frame: Cycle 1 (21 days, from Cycle 1 Day 1 predose to Cycle 2 Day 1 predose)]
measure: Terminal half-life (T1/2) following a single dose of 23ME-01473
timeFrame: [Time Frame: Cycle 1 (21 days, from Cycle 1 Day 1 predose to Cycle 2 Day 1 predose]
measure: Maximum serum concentration (Cmax) following multiple doses of 23ME-01473
timeFrame: [Time Frame: Cycle 4 (21 days, from Cycle 4 Day 1 predose to Cycle 5 Day 1 predose)]
measure: Time of maximum serum concentration (Tmax) following multiple doses of 23ME-01473
timeFrame: [Time Frame: Cycle 4 (21 days, from Cycle 4 Day 1 predose to Cycle 5 Day 1 predose)]
measure: Area under the concentration-time curve from time zero to the end of the dosing interval (AUCtau) following multiple doses of 23ME-01473
timeFrame: [Time Frame: Cycle 4 (21 days, from Cycle 4 Day 1 predose to Cycle 5 Day 1 predose)]
measure: Serum concentration at the end of the dosing interval (Ctau) following multiple doses of 23ME-01473
timeFrame: [Time Frame: Cycle 4 (21 days, from Cycle 4 Day 1 predose to Cycle 5 Day 1 predose)]
measure: Terminal half-life (T1/2) following multiple doses of 23ME-01473
timeFrame: [Time Frame: Cycle 4 (21 days, from Cycle 4 Day 1 predose to Cycle 5 Day 1 predose)]
Other outcomes:
Locations:
city: Grand Rapids
country: United States
facility: START Midwest
state: Michigan
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: San Antonio
country: United States
facility: START Center for Cancer Care
state: Texas
Study officials:
affiliation: 23andMe, Inc.
name: Jennifer Low, M.D,Ph.D
role: STUDY_DIRECTOR
References: