Study of 23ME-01473 in Patients With Advanced Solid Malignancies

A Phase 1/2a, Multicenter, Open-label, Dose Escalation and Expansion Study of Intravenously Administered 23ME-01473 in Participants With Advanced Solid Malignancies

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.

Study Overview

• Status: Terminated
• Conditions: Solid Tumor
• Intervention / Treatment: Drug: 23ME-01473

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.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Grand Rapids, Michigan, United States, 49546
      • Start Midwest
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University
  • Texas
    • San Antonio, Texas, United States, 78229
      • START Center for Cancer Care

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1; Participants will receive escalating doses of 23ME-01473	Drug: 23ME-01473; 23Me-01473 given by intravenous infusion

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	ORR based on investigator assessment against RECIST 1.1 criteria	From baseline until disease progression (up to 5 years)
Duration of response (DoR)	Duration of response based on investigator assessment against RECIST 1.1 criteria	From baseline until disease progression (up to 5 years)
Disease Control Rate (DCR)	Disease control rate based on investigator assessment against RECIST 1.1 criteria	From baseline until disease progression (up to 5 years)
Progression free survival (PFS)	Progression free survival based on investigator assessment against RECIST 1.1 criteria	From baseline until disease progression (up to 5 years)
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)]
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)]
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)]
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]
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)]

Collaborators and Investigators

• Sponsor: 23andMe, Inc.
• Investigators: Study Director: Jennifer Low, M.D,Ph.D, 23andMe, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): March 7, 2024
• Primary Completion (Actual): November 10, 2024
• Study Completion (Actual): November 10, 2024

Study Registration Dates

• First Submitted: February 8, 2024
• First Submitted That Met QC Criteria: February 26, 2024
• First Posted (Actual): March 4, 2024

Study Record Updates

• Last Update Posted (Estimated): December 4, 2024
• Last Update Submitted That Met QC Criteria: December 2, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: Cancer; Immunotherapy; Phase 1; Oncology; Solid Tumor; NK; ULBP6
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: 23ME-01473-CLIN-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No