Cavrotolimod Granted Orphan Drug Designation for Merkel Cell Carcinoma

The FDA granted Orphan Drug Designation to cavrotolimod, for the treatment of patients with Merkel cell carcinoma, announced Exicure, Inc, in a press release.

The FDA granted Orphan Drug Designation to cavrotolimod (AST-008), for the treatment of patients with Merkel cell carcinoma (MCC), announced Exicure, Inc, in a press release.

“We are excited to have been granted Orphan Drug Designation by the FDA for cavrotolimod for MCC,” said Douglas Feltner, MD, chief medical officer of Exicure, in the press release. “This designation marks significant progress toward our goal of fulfilling the unmet medical need and finding a treatment for Merkel cell carcinoma patients.”

Cavrotolimod, an SNA consisting of toll-like receptor 9 agonists, is currently under investigation in a phase 1b/2 open-label, 2-part, multicenter trial (NCT03684785). The study is designed to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary activity of the agent when injected intratumorally. In the study, cavrotolimod is used both alone and in combination with intravenous pembrolizumab (Keytruda) or cemiplimab (Libtayo) in patients with MCC, cutaneous squamous cell carcinoma, and advanced solid tumors. Currently, eligible patients are being recruited for the study. The target enrollment is 130 patients.

Patients are eligible if they are 18 years of age or older with at least 1 tumor lesion amenable to repeated intratumoral injection via palpation or ultrasound, evaluable disease per RECIST 1.1, and adequate organ function.

The trial follows a 3 + 3 design, in which the dose of cavrotolimod will be escalated accordingly in the phase 1b portion with 5 dose cohorts. Pembrolizumab will be administered at a fixed dose. Treatment will continue in phase 1b until the maximum tolerated dose for the phase 2 study is determined. The primary end point being assessed in phase 1b is safety, as determined by the incidence of adverse events. Based on prior research, the most commonly reported adverse events related to cavrotolimod are injection site reactions and flu-like symptoms.

In phase 2, the study of cavrotolimod will evaluate the agent in combination with either pembrolizumab or cemiplimab in 2 expansion cohorts. Phase 2 will follow a modified Simon 2-stage optimal design. The secondary end points explored in the study include objective response rate, changes in correlative biomarkers including tumor-infiltrating lymphocytes, and changes in gene expression profiles at baseline.

Prior to receiving an Orphan Drug Designation, cavrotolimod was granted Fast Track designation by the FDA for the treatment of both MCC and cutaneous squamous cell carcinoma (CSCC) in the advanced/metastatic setting after progression on anti–PD-1/PD-L1 antibodies.


Exicure Granted Orphan Drug Designation by the U.S. Food and Drug Administration for Cavrotolimod. News release. Exicure, Inc. March 3, 2021. Accessed March 4, 2021.

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