The Food and Drug Administration (FDA)’s Orphan Drug designation has been granted to cavrotolimod (AST-008; Exicure Inc) for the treatment of Merkel cell carcinoma.

Cavrotolimod is a toll-like receptor 9 agonist that is designed to induce anticancer immune responses through proprietary spherical nucleic acid (SNA™) technology.  The investigational therapy is being evaluated in combination with pembrolizumab or cemiplimab in a phase 1b/2 study in patients with Merkel cell carcinoma, cutaneous squamous cell carcinoma, and other advanced solid tumors ( NCT03684785).

Data from the phase 1b dose-escalation stage, which was designed to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of cavrotolimod alone and in combination with pembrolizumab, showed a confirmed overall response rate (ORR) of 21% (4/19 patients; 1 complete response and 3 partial responses) for the combination immunotherapy regimen. Among patients who received the highest dose of cavrotolimod (32mg), the ORR was 33% (2/6 patients); this dose was selected as the dose for the phase 2 portion of the study.

As for safety, the most commonly reported adverse events were injection site reactions and flu-like symptoms; no dose-limiting toxicities or serious treatment-emergent adverse events were reported in the phase 1b stage.

The phase 2 dose expansion stage, which was initiated in June 2020, includes patients with Merkel cell carcinoma and those with cutaneous squamous cell carcinoma. Each cohort is expected to enroll up to 29 patients whose tumors have progressed on anti-PD-1/PD-L1 monotherapy.


1.      Exicure granted Orphan Drug designation by the US Food and Drug Administration for cavrotolimod. [press release]. Chicago, IL and Cambridge, MA: Exicure; March 3, 2021.

2.      Exicure presents positive clinical data with cavrotolimod at The Society for Immunotherapy of Cancer (SITC) 35th Anniversary Annual Meeting. [press release]. Chicago, IL and Cambridge, MA: Exicure; November 9, 2020.

3.      Exicure announces first patient dosed in phase 2 Merkel Cell carcinoma trial of cavrotolimod (AST-008). [press release]. Chicago, IL and Cambridge, MA: Exicure; June 16, 2020.