On September 16, 2020 Exicure, Inc. (NASDAQ: XCUR), the pioneer in gene regulatory and immunotherapeutic drugs utilizing proprietary spherical nucleic acid (SNA) technology, reported that it will host a virtual Key Opinion Leader (KOL) event to present preliminary Phase 1b efficacy and safety data for its intratumoral product candidate, cavrotolimod, the company’s SNA-enabled TLR9 agonist being developed for the treatment of solid tumors, in combination with pembrolizumab (Press release, Exicure, SEP 16, 2020, View Source [SID1234565232]). The event will take place today from 10:30 am – 12:00 pm ET.
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The principal investigators of the Phase 1b portion of the trial, Dr. Steven O’Day and Dr. Shailender Bhatia, will be presenting and joining Exicure’s leadership team in discussing the clinical data and trial progress to date.
"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.
The event will be webcast live today, September 16th at 10:30 am ET through a link on the Events and Presentations section of Exicure’s website. An archived webcast will also be available on Exicure’s website following the event. To RSVP for the event, please use the link here (View Source) or email [email protected].
Description of the Trial
The objectives of the Phase 1b dose-escalation stage of the clinical trial were to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of cavrotolimod alone and in combination with pembrolizumab, and to identify a recommended Phase 2 dose. Cavrotolimod was dosed weekly for 8 weeks then every three weeks thereafter. Pembrolizumab was added to the treatment regimen starting in week three of the study. The first two weeks of the trial, the period in which only cavrotolimod was dosed, allowed for the assessment of cavrotolimod safety, tolerability, pharmacokinetics and pharmacodynamics alone. Efficacy was assessed every 12 weeks. Twenty patients have been enrolled and dosed in the dose-escalation stage of the trial consisting of: ten (10) melanoma patients, five (5) MCC patients, two (2) CSCC patients, two (2) head and neck squamous cell carcinoma patients, and one (1) leiomyosarcoma patient. At the
time of enrollment, 85% of patients were experiencing progressive disease while on anti-PD-1 antibody therapy.
Highlights from the data
Highlights from the data update include:
–Confirmed ORR 21% (4/19 patients) overall in the Phase 1b dose-escalation stage
–Confirmed ORR 33% (2/6 patients) in the highest dose cohort (32 mg), which was selected as Phase 2 recommended dose
–Overall responses occurred in two patients with advanced MCC and two patients with melanoma
–Three of four responders were progressing on anti-PD-1 therapy at the time of enrollment
–In addition to the four confirmed responses, target tumor shrinkage occurred in one CSCC patient and two melanoma patients. Systemic (abscopal) effects were observed, with regression in noninjected tumors distant from injected lesions.
–The cavrotolimod pharmacodynamic profile corroborated the efficacy data, as increased serum cytokines/chemokines, activated immune cells, and tumor infiltration by immune cells were observed.
The median duration of response has not been reached as all four confirmed responders have not progressed after a median follow-up of 11 months. The longest response to date is 16 months from initial dosing and is ongoing as of the data cut-off date.
Exicure continues to observe that cavrotolimod is well tolerated with 98% of all treatment-emergent adverse events (AEs) assessed as Grade 1 or 2 in severity. No treatment-related serious adverse events were reported to date. The most common adverse events were flu-like symptoms and injection site reactions, which are commonly expected effects from a TLR9 mechanism of action.
Updated guidance
Exicure expects to provide interim ORR results from the MCC and CSCC cohorts of the Phase 2 portion of the clinical trial in the first half of 2021 and final ORR results by year end 2021.