Title
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

Description
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.

Objective
Primary Objectives:
-To evaluate the safety and feasibility of a single IV infusion of SynKIR-110 in subjects with advanced mesothelin-expressing solid tumors (ovarian cancer, cholangiocarcinoma, or mesothelioma)

Secondary Objectives:
-To identify the maximum tolerated dose (MTD)/maximum feasible dose (MFD) of SynKIR-110 and to identify a recommended Phase 2 dose

Treatment Experimental: SynKIR-110
Single dose gravity drip IV administration
Biological: SynKIR-110, Autologous T cells Transduced with Mesothelin KIR-CAR
Autologous T cells Transduced with Mesothelin KIR-CAR

Key Eligibility 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

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

Applicable Disease Sites
Gastrointestinal cancers, other; Liver; Lung; Ovary

Participating Institutions
UW Health Eastpark Medical Center; UW Health University Hospital