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

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 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 confirmed disease progression, whichever occurs first, 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 treated 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 treated at the MTD/MFD to further assess safety and potential activity of SynKIR-110.

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.
• 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