SynKIR-110 for Mesothelin Expressing Ovarian Cancer, Cholangiocarcinoma or Mesothelioma

Study Overview
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Brief Summary
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This first-in-human (FIH) trial is designed to assess the safety, feasibility, and potential activity of a single intravenous (IV) dose of SynKIR-110 administered to subjects with mesothelin-expressing advanced ovarian cancer, mesothelioma, and cholangiocarcinoma.

Detailed Description
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This is a Phase 1, FIH, multicenter, open-label, dose-escalation pilot study of a single IV gravity drip infusion of SynKIR-110 in subjects with advanced, mesothelin-expressing tumors (ovarian cancer, primary peritoneal cancer, fallopian tube cancer, cholangiocarcinoma, or mesothelioma). Up to 42 subjects will be assessed to determine the safety and feasibility of treatment with SynKIR-110. Informed consent will be obtained from subjects prior to participation in this study. The study includes an initial tumor biomarker screening, followed by an enrollment screening period (which includes pre-leukapheresis safety/eligibility and leukapheresis visits), treatment period (administration of non-myeloablative lymphodepleting chemotherapy followed by a single infusion of investigational product), and a 12-month follow-up period or until disease progression. Subjects will be followed for 12 months or until disease progression, at which point they will be invited to participate in a long-term safety follow-up study. Up to 6 cohorts of 3 to 6 subjects per cohort will be assessed to determine the safety and feasibility of treatment with SynKIR-110. Doses will be escalated following a standard 3 + 3 design until either an MTD or MFD is reached. An additional 6 to 9 subjects will be enrolled at the MTD/MFD to further assess safety and potential activity of SynKIR-110.

Official Title
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A Phase 1 Study of SynKIR-110, Autologous T Cells Transduced With Mesothelin KIR-CAR, in Subjects With Mesothelin-Expressing Advanced Ovarian Cancer, Cholangiocarcinoma, or Mesothelioma

Conditions
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Ovarian Cancer, Cholangiocarcinoma Recurrent, Mesothelioma, Malignant

Intervention / Treatment
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* Biological: SynKIR-110, Autologous T cells Transduced with Mesothelin KIR-CAR


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathologically confirmed recurrent or relapsed advanced ovarian cancer, primary peritoneal cancer, fallopian tube cancer, cholangiocarcinoma, or epithelial mesothelioma (pleural or peritoneal) after at least 1 prior line of systemic therapy for advanced disease Adult 18 years of age or older. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. For ovarian cancer and mesothelioma, tumor expression of mesothelin ≥50% of tumor cells with ≥2+ staining intensity (on a scale of 0 to 3). For cholangiocarcinoma ≥10% of cells at any staining intensity (≥1+). Has at least 1 measurable lesion by iRECIST for ovarian cancer or cholangiocarcinoma or lesions measurable for mRECIST for mesothelioma. Satisfactory Blood coagulation parameters: Satisfactory organ and bone marrow function Exclusion Criteria: Active invasive cancers other than mesothelioma, cholangiocarcinoma, and ovarian unless surgically and medically cured without evidence of recurrent disease for 5 years. History of T or B cell malignancies or previous gene-engineered T cell therapies. Sarcomatoid/biphasic mesothelioma. Pulmonary exclusions: Have acquired hereditary, congenital immunodeficiency or have recognized immunodeficiency disease Active hepatitis B, active hepatitis C, or any HIV infection at the time of screening Active autoimmune disease

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SynKIR-110<br>Single dose gravity drip IV administration | Biological: SynKIR-110, Autologous T cells Transduced with Mesothelin KIR-CAR<br>* Autologous T cells Transduced with Mesothelin KIR-CAR<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and feasibility of SynKIR-110 | • The incidence, frequency, and severity of TEAEs, incidence of AEs related to native mesothelin-expressing tissues, • Incidence of CRS and/or neurologic toxicity | Date of enrollment through date of last patient visit, up to 36 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Define the MTD or MFD of SynKIR-110 | Define the MTD or MFD of SynKIR-110 | Date of enrollment until the MTD is defined, up to 18 months |