Mesothelioma KIR-CAR T-cell Therapy Gets FDA Fast Track Designation
Verismo Therapeutics’ SynKIR-110 previously received orphan drug designation from the FDA.
Verismo Therapeutics’ SynKIR-110, an investigational killer immunoglobulin-like receptor - chimeric antigen receptor (KIR-CAR) T-cell therapy intended to treat mesothelin-expressing cancers including malignant pleural mesothelioma, has been granted fast track designation by the FDA.1
SynKIR-110 consists of autologous T-cells that have been transduced with a mesothelin KIR-CAR. The therapy also incorporatesa DAP12 activation pathway which is intended to improve persistence. SynKIR-110 is being evaluated in a phase 1 clinical trial (NCT05568680) for patients with mesothelin-expressing advanced ovarian cancer, mesothelioma, and cholangiocarcinoma. Verismo Therapeutics originally announced the clearance of its investigational new drug (IND) application for the trial in September of last year.2 Later that same month, the therapy received orphan drug designation from the FDA.3
"We are thrilled to receive fast track designation from the FDA," Bryan Kim, DMD, the co-founder and chief executive officer of Verismo Therapeutics, said in a statement.1 "This designation is an important milestone in our efforts to bring this potentially life-saving drug to patients who are in need of new treatment options."
The multicenter, open-label, dose-escalation trial is seeking to recruit an estimated 42 patients aged 18 years or older with advanced ovarian cancer, primary peritoneal cancer, fallopian tube cancer, cholangiocarcinoma, or pleural or peritoneal epithelial mesothelioma. Participants are required to have cancer that is recurrent or relapsed after 1 or more prior lines of systemic therapy for advanced disease. Additionally, participants must have an Eastern Cooperative Oncology Group score of 0-1; satisfactory blood coagulation parameters; and satisfactory organ and bone marrow function. Patients with ovarian cancer and mesothelioma must have mesothelin expression on at least 50% of tumor cells with 2 or greater staining intensity; patients with cholangiocarcinoma must have mesothelin expression on at least 10% of tumor cells with 1 or greater staining intensity. Patients with ovarian cancer or cholangiocarcinoma must have at least 1 measurable lesion by iRECIST; patients with mesothelioma must have lesions measurable for mRECIST. Patients with a history of T-cell or B-cell malignancies; patients with sarcomatoid/biphasic mesothelioma; patients with pulmonary exclusions; patients who previously received gene-engineered T-cell therapies; and those with active invasive cancers other than mesothelioma, cholangiocarcinoma, or ovarian cancer that have not been surgically and medically cured without evidence of recurrence for 5 years will be excluded from the study. Additional exclusion criteria relate to patient health status.
The trial’s primary end points include the incidence, frequency, and severity of treatment-emergent adverse events (AEs); the incidence of AEs related to native mesothelin-expressing tissues; and the incidence of cytokine release syndrome and neurologic toxicity. The trial’s secondary end point is the determination of the maximum tolerated dose or the maximum feasible dose. The study has an estimated primary completion date of March 15, 2026, and an estimated completion date of March 30, 2026.
"SynKIR-110 is the first product to use the novel KIR-CAR platform,” Laura Johnson, PhD, chief scientific officer, Verismo, said in a statement when the company submitted the trial’s IND.4 “Our technology incorporates a natural on/off switch that allows KIR-CAR T-cells to rest when not exposed to tumor antigens, as well as providing an enhanced cell-surface stability of the KIR-CAR. These enhancements will allow KIR-CAR T-cells to better cope with the harsh tumor microenvironment of solid tumors and, potentially, lead to better outcomes for our patients."
