On November 9, 2020 Exicure, Inc. (NASDAQ: XCUR), the pioneer in gene regulatory and immunotherapeutic drugs utilizing proprietary spherical nucleic acid (SNA) technology, reported the presentation of updated Phase 1b data from the ongoing Phase 1b/2 clinical trial evaluating intratumoral cavrotolimod (AST-008), the Company’s SNA-enabled TLR9 agonist, in combination with the anti-PD-1 therapies pembrolizumab (KEYTRUDA) or cemiplimab (LIBTAYO), in patients with Merkel cell carcinoma, cutaneous squamous cell carcinoma, and other advanced solid tumors (NCT03684785) (Press release, Exicure, NOV 9, 2020, View Source [SID1234570535]).

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The Phase 1b dose-escalation stage was designed to assess 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 intratumorally once weekly for 8 weeks and subsequently once every 3 weeks. Following an initial cavrotolimod monotherapy period, pembrolizumab was initiated at week 3 and dosed in combination with cavrotolimod once every 3 weeks. The Phase 1b stage enrolled patients with locally advanced or metastatic melanoma (n=10), Merkel cell carcinoma (n=5), cutaneous squamous cell carcinoma (n=2), head and neck squamous cell carcinoma (n=2), and leiomyosarcoma (n=1).

Updated data from the Phase 1b stage demonstrated that the combination of cavrotolimod and pembrolizumab continued to be well tolerated, with a confirmed overall response rate (ORR) of 21% (4/19 patients) according to RECIST v1.1 criteria. The combination immunotherapy regimen induced durable and systemic anti-tumor responses in patients with advanced solid tumors who previously progressed on anti-PD-1 therapy. At the time of enrollment in the clinical trial, 85% of patients were experiencing progressive disease despite treatment with PD-1 blockade and 65% of patients had been treated with 2 or more lines of systemic therapy.

Highlights from the Phase 1b Dose-Escalation Stage

– The RECIST-confirmed ORR was 21% (4/19 patients) overall in the Phase 1b dose-escalation stage, reflecting 1 complete response and 3 partial responses.

– In the highest cavrotolimod dose cohort (32 mg), which was selected as the Phase 2 dose, the RECIST-confirmed ORR was 33% (2/6 patients).

– Responses were durable and ongoing at the time of data analysis, with progression-free survival exceeding 6 months in all 4 responders and 16 months in 2 responders.

– 85% of patients overall (17/20 patients) and 75% of responders (3/4) were progressing on anti-PD-1 therapy at the time of trial enrollment.

– Systemic (abscopal) effects were observed, with shrinkage of regional or distant noninjected tumors.

– The majority (98%) of treatment-related adverse events were grade 1 or grade 2. No dose-limiting toxicities and no treatment-related serious adverse events were reported in the Phase 1b stage. The most common adverse events were flu-like symptoms and injection site reactions, consistent with other adverse events experienced with local and systemic immune activation associated with TLR9 agonism.

Details of the poster presentation are as follows:

Title: Safety and preliminary efficacy of intratumoral cavrotolimod (AST-008), a spherical nucleic acid TLR9 agonist, in combination with pembrolizumab in patients with advanced solid tumors

Authors: Steven J. O’Day, Cesar A. Perez, Trisha M. Wise-Draper, Glenn J. Hanna, Shailender Bhatia, Ciara M. Kelly, Theresa M. Medina, Douglas E. Laux, Adil Daud, Sunandana Chandra, Montaser Shaheen, Ling Gao, Melissa A. Burgess, Leonel Hernandez-Aya, Emil M. deGoma, Weston L. Daniel, Douglas E. Feltner, Laurel Sindelar, Robert E. Michel, Alice S. Bexon, Martin Bexon, and Mohammed M. Milhem

Poster/Abstract Number: 423

The abstract and poster will be available on the SITC (Free SITC Whitepaper) website once the conference begins on Monday, November 9 at 8:00 a.m. EST. The poster will also be made available on the Exicure website.

Live Q&A will take place Wednesday, November 11 from 5:15–5:45 p.m. EST and Friday, November 13 from 4:40–5:10 p.m. EST.