FDA Grants Fast Track Designation to SynKIR-110 for Mesothelioma

The FDA has granted a fast track designation to SynKIR-110 for the treatment of patients with mesothelioma, according to an announcement from Verismo Therapeutics.¹

“We are thrilled to receive fast track designation from the FDA,” Bryan Kim, DMD, co-founder and chief executive officer of Verismo Therapeutics, said in a press release. “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.”

A pioneer of the KIR-CAR platform, Verismo is focused on the development of innovative treatments for patients with serious and life-threatening conditions. The KIR-CAR platform harnesses a modified NK-like receptor designed to improve treatment persistence and efficacy against aggressive solid tumors.

In preclinical animal models, the dual-chain CAR T-cell therapy has shown sustained antitumor T-cell activity in solid tumors regardless of the microenvironment, including in those who are refractory to traditional CAR T-cell therapies. Moreover, sustained chimeric receptor expression and improved KIR-CAR T-cell persistence is made possible through DAP12, which functions as a novel costimulatory molecule for T cells.

Furthermore, the KIR-CAR platform can be used in conjunction with emerging technologies, including in vivo gene engineering, advanced cell manufacturing and reprogramming, combination therapies, and allogeneic cellular therapies.

SynKIR-110 is an investigational new drug under evaluation in a phase 1, multicenter trial (NCT05568680) for the treatment of patients mesothelin-expressing mesothelioma, cholangiocarcinoma, and ovarian cancer.

The first-in-human, multicenter, open-label, dose-escalation pilot study will evaluate a single intravenous gravity drip infusion of SynKIR-110 in patients with advanced, mesothelin-expressing tumors. Up to 42 patients will be evaluated for safety and feasibility of treatment with SynKIR-110.

To be eligible for enrollment in the trial, patients must have pathologically confirmed recurrent or relapsed advanced ovarian cancer, primary peritoneal cancer, fallopian tube cancer, cholangiocarcinoma, or epithelial mesothelioma following treatment with at least 1 prior line of systemic therapy for advanced disease.² Patients with ovarian cancer and mesothelioma must have at least 50% tumor expression of mesothelin on tumor cells with at least 2+ staining intensity. Patients with cholangiocarcinoma must have at least 10% expression of mesothelin on tumor cells and staining intensity of at least 1+.

Prior to treatment, patients will undergo an initial tumor biomarker screening, followed by an enrollment screening period, which includes pre-leukapheresis safety/eligibility and leukapheresis visits. Subsequently, patients will receive non-myeloablative lymphodepleting chemotherapy followed by a single infusion of Syn-KIR-110.

Patients will undergo follow-up for 12 months or until disease progression, at which point they will have the option to enroll in a long-term safety follow-up study.

The study will consist of up to 6 cohorts of 3 to 6 subjects. Doses of SynKIR-110 will be escalated following a standard 3 + 3 design until the maximum tolerated dose (MTD) or maximum feasible dose (MFD) is reached. An additional 6 to 9 patients will be enrolled at the MTD/MFD to further determine safety and efficacy of the agent.

Safety and feasibility of SynKIR-110 served as the primary objectives of the trial. Secondary objectives included defining the MTD or MFD of SynKIR-110.

References

1. Verismo Therapeutics secures fast track designation from the U.S. Food and Drug Administration (FDA) for SynKIR-110. News release. Verismo Therapeutics. April 5, 2023. Accessed April 6, 2023. https://www.prnewswire.com/news-releases/
2. SynKIR-110 for mesothelin expressing ovarian cancer, cholangiocarcinoma or mesothelioma. ClinicalTrials.gov. Updated April 6, 2023. Accessed April 6, 2023. https://clinicaltrials.gov/ct2/show/NCT05568680