Exicure Announces Positive Phase Ib Trial Results for Solid Tumor Treatment


On Wednesday, Exicure announced positive results from its Phase Ib trial evaluating cavrotolimod, its SNA-enabled TLR9 agonist, that is being developed for the treatment of solid tumors, in combination with pembrolizumab.

The goal of the Phase Ib dose-escalation stage of the clinical trial was to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of cavrotolimod alone and in combination with pembrolizumab to identify a Phase II dose. In the trial, cavrotolimod was dosed weekly for eight weeks, and then every three weeks thereafter. Pembrolizumab was added to the treatment regiment beginning in Week 3 of the trial.

During the first two weeks of the study, the safety, tolerability, pharmacokinetics and pharmacodynamics of cavrotolimod were assessed. Efficacy was gauged every 12 weeks.

A total of 20 patients were enrolled in the trial, and at the time, 85% were experiencing progressive disease while on an anti-PD-1 antibody therapy.

The researchers determined that there was a 21% overall response rate (ORR) in the Phase Ib dose-escalation stage, and a 33% ORR at the highest dose cohort (32mg), which was ultimately selected as the Phase 2 recommended dose.

In addition to the recorded ORRs, target tumor shrinkage was seen in one patient with Cutaneous Squamous Cell Carcinoma and two melanoma patients. Overall responses occurred in two patients with advanced Merkel Cell Carcinoma and two melanoma patients.

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No treatment-related serious adverse events have been reported to date. The most common side effects were flu-like symptoms and injection site reactions.

"We are excited by the durable responses we have seen in anti-PD-1 refractory patients, and look forward to further exploring the efficacy of cavrotolimod in these highly treatment refractory Merkel cell carcinoma and cutaneous squamous cell carcinoma patients," said Dr. Douglas Feltner, Chief Medical Officer of Exicure.

Back in June, Exicure announced that the first patient enrolled in its Phase II dose expansion stage of the cavrotolimod Phase Ib/II clinical trial had received dosing.

“We believe this milestone marks an important step toward fulfilling an unmet treatment need for Merkel Cell Carcinoma patients who have been resistant to checkpoint inhibitor antibody therapy,” Feltner said at the time of the announcement.

The Phase II dose expansion stage includes two cohorts of patients with advanced or metastatic cancer. Specifically, the subjects have either Merkel Cell Carcinoma or Cutaneous Squamous Cell Carcinoma.

The dose expansion stage is specifically meant to assess the anti-tumor response rate of cavrotolimod, along with a checkpoint inhibitor treatment. In addition, researchers will look at the safety and tolerability of the combination, along with the drug pharmacodynamics and pharmacokinetics. The subjects who are enrolled in the trial must have recently documented tumor progression despite anti-PD-1 or anti-PD-L1 antibody monotherapy.

Cavrotolimod consists of toll-like receptor 9 agonists designed for immuno-oncology applications. Exicure originally announced preliminary results from its Phase Ib trial back in December 2019. Data showed that the administration of cavrotolimod, alone or in combination with pembrolizumab, produced cytokine and chemokine expression and immune cell activation.

Pembrolizumab, which is marketed by Merck as Keytruda, also received approval in Japan for the treatment of certain patients with Esophageal Squamous Cell Carcinoma (ESCC) back in August of this year. The anti-PD-1 therapy works by increasing the ability of the body’s immune system to detect and combat tumor cells. It is a humanized monoclonal antibody that blocks interaction between PD-1 and its ligands, PD-L1 and PD-L2, which activates T lymphocytes.

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