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

Phase 1

Recruiting

• Conditions: Mesothelioma, Malignant; Ovarian Cancer; Cholangiocarcinoma Recurrent
• Interventions: Biological: SynKIR-110, Autologous T cells Transduced with Mesothelin KIR-CAR

• Registration Number: NCT05568680
• Lead Sponsor: Verismo Therapeutics

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2022-09-28
• Study First Submitted QC: 2022-10-05
• Study First Posted: 2022-10-06
• Study Start: 2023-03-30
• Status Verified: 2025-03
• Last Update Submitted: 2025-04-08
• Last Update Posted: 2025-04-11
• Primary Completion: 2027-12
• Study Completion: 2027-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 42

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
SynKIR-110	SynKIR-110, Autologous T cells Transduced with Mesothelin KIR-CAR	Single dose gravity drip IV administration

Primary Outcome Measures

Name	Time	Method
Safety and Feasibility of SynKIR-110	Up to 12 months	* The incidence, frequency, and severity of TEAEs, incidence of AEs related to native mesothelin-expressing tissues, Incidence of CRS and/or neurologic toxicity; * Frequency of subjects who pass screening to enrollment but do not receive SynKIR-110

Secondary Outcome Measures

Name	Time	Method
Define the maximum tolerated dose (MTD)/maximum feasible dose (MFD) of SynKIR-110 and to identify a recommended Phase 2 dose	Up to 12 months	Define the MTD or MFD of SynKIR-110

Trial Locations

Locations (4)

University of Kansas Cancer Center; 🇺🇸 Westwood, Kansas, United States

University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States

MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

University of Wisconsin Carbone Cancer Center; 🇺🇸 Madison, Wisconsin, United States