A First-in-human Phase I/IIa, Multicenter, Open-Label, Dose-Escalation and Expansion Study of Intravenously Administered 23ME-00610 in Patients With Advanced Solid Malignancies
Study Identifier:
23ME-00610-CLIN-001
CT.gov Identifier:
EudraCT Identifier:
N/A
EU Trial (CTIS) Number:
N/A
Study Contact Information:
Terminated/Withdrawn
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Study Summary
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.
Phase 2a portion: To evaluate the anti-tumor activity of the 23ME-00610 monotherapy in a number of previously disclosed expansion cohorts and will further characterize the safety, tolerability, pharmacokinetic and pharmacodynamic profile of 23ME-00610.
The primary objective was evaluation of clinical antitumor activity.
Exploratory biomarkers included CD200/R1 tumor expression, host genotyping, and peripheral target engagement. Adverse events (AEs) were assessed using CTCAE v5. Disease assessments were conducted every 8 weeks, and response was assessed by investigators using RECIST 1.1 criteria.
Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
Phase
The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
I/II
Sex
Female & Male
Age
12+ years
Study Drug
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Study Status
Indicates the current recruitment status or the expanded access status
Terminated/Withdrawn
Requirements information
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.
- Part B:
- 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:
- TMB-H solid cancer that has been confirmed by the FoundationOne CDx assay or other industry/institutional equivalent platform form TMB 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.
- 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.
- 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.
- 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;
- Life expectancy ≥ 12 weeks
- 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.
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 >or= 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
- Human Immunodeficiency Virus (HIV) infection, except those who meet the following criteria: CD4+ T cells >or= 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.
- Prior radiation therapy with an inadequate washout between the last dose and the start of study drug, defined as follows: 1) at least 2 weeks for palliative radiation to the extremities for osseous bone metastases is required; 2) at least 4 weeks for radiation to the chest, brain, or visceral organs is required; and 3) at least 6 weeks for large-field radiation is required.
- Prior anticancer therapy, including chemotherapy, targeted therapy, biological therapy or immune-checkpoint inhibitors within 4 weeks or 5 drug half-lives (whichever is shorter)
- History of another malignancy in the previous 2 years, unless cured by surgery alone and continuously disease free.
- Recent history of cardiovascular disease
- Uncontrolled or symptomatic CNS (central nervous system) metastases and/or carcinomatous meningitis
- Exclusion criteria included active autoimmune disease requiring immunosuppressive therapy and Grade ≥ 3 immune-mediated toxicity related to prior immunotherapy that led to discontinuation.
- Exploratory biomarkers included CD200R1 and CD200 tumor expression by IHC in archival tissue, germline genotyping, and polygenic risk score calculation for immune-mediated and cancer phenotypes. At least 15 patients were accrued to characterize target-specific biomarkers and efficacy.
Clinical Study Information for Healthcare Providers
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Study Locations
Location
Investigator
Status
Condition(s) Treated at Site
Location
START San Antonio
San Antonio, TX, United States, 78229
Investigator
Drew Rasco
Status
Recruitment Complete
Condition(s) Treated at Site
Solid Tumor
Renal
Ovarian
Fallopian Tube
Primary Peritoneal
Neuroendocrine
Biomarkers
Gene Mutations
Small Cell Lung