Clinical trial NCT05568680: SynKIR-110 for Mesothelin Expressing Ovarian Cancer, Cholangiocarcinoma or Mesothelioma
Official 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Ovarian Cancer
Cholangiocarcinoma Recurrent
Mesothelioma, Malignant
Lead sponsor: Verismo Therapeutics
Sponsor class: INDUSTRY
First posted: 2022-10-06
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Safety and Feasibility of SynKIR-110
timeFrame: Up to 12 months
Secondary outcomes:
measure: Define the maximum tolerated dose (MTD)/maximum feasible dose (MFD) of SynKIR-110 and to identify a recommended Phase 2 dose
timeFrame: Up to 12 months
Other outcomes:
Locations:
city: Westwood
country: United States
facility: University of Kansas Cancer Center
state: Kansas
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Madison
country: United States
facility: University of Wisconsin Carbone Cancer Center
state: Wisconsin
Study officials:
affiliation: Verismo Therapeutics
name: Laura Johnson, PhD
role: STUDY_DIRECTOR
References: