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304 Intratumoral injection of CMP-001, a toll-like receptor 9 (TLR9) agonist, in combination with pembrolizumab reversed programmed death receptor 1 (PD-1) blockade resistance in advanced melanoma
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  1. Mohammed Milhem1,
  2. Yousef Zakharia1,
  3. Diwakar Davar2,
  4. Elizabeth Buchbinder3,
  5. Theresa Medina4,
  6. Adil Daud5,
  7. Antoni Ribas6,
  8. Jiaxin Niu7,
  9. Geoffrey Gibney8,
  10. Kim Margolin9,
  11. Anthony Olszanski10,
  12. Inderjit Mehmi11,
  13. Takami Sato12,
  14. Montaser Shaheen13,
  15. Aaron Morris14,
  16. David Mauro15,
  17. Katie Campbell6,
  18. Heather Kelley14,
  19. Riyue Bao2,
  20. George Weiner1,
  21. Jason Luke2,
  22. Arthur Krieg14,
  23. James Wooldridge14 and
  24. John Kirkwood2
  1. 1University of Iowa, Iowa City, IA, USA
  2. 2University of Pittsburgh Medical Center, Pittsburgh, PA, USA
  3. 3Dana-Farber Cancer Institute, Boston, MA, USA
  4. 4University of Colorado Denver, Aurora, CO, USA
  5. 5University of California San Francisco, San Francisco, CA, USA
  6. 6University of California Los Angeles, Los Angeles, CA, USA
  7. 7Banner MD Anderson Cancer Center, Gilbert, AZ, USA
  8. 8Georgetown Lombardi Comprehensive Cancer, Washington, DC, USA
  9. 9City of Hope, Duarte, CA, USA
  10. 10Fox Chase Cancer Center, Philadelphia, PA, USA
  11. 11The Angeles Clinic and Research Institut, Los Angeles, CA, USA
  12. 12Thomas Jefferson University, Philadelphia, PA, USA
  13. 13University of Arizona, Tucson, AZ, USA
  14. 14Checkmate Pharmaceuticals Inc., Cambridge, MA, USA
  15. 15Prelude Therapeutics Inc., Wilmington, DE, USA
  • Journal for ImmunoTherapy of Cancer (JITC) preprint. The copyright holder for this preprint is the author/funder, who has granted JITC permission to display the preprint. All rights reserved. No reuse allowed without permission.

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Abstract

Background Therapeutic options are limited for patients with advanced melanoma that is refractory to PD-1 blockade. This study was performed in this patient population to assess the safety and antitumor activity of CMP-001, a CpG-A TLR9 agonist packaged within a virus-like particle.

Methods Patients were eligible for this 2-part, open-label, multicenter, phase 1b study if they had metastatic/unresectable melanoma and stable disease after =12 weeks or progressive disease (PD) on/after anti-PD-1 therapy. Part 1 evaluated CMP-001 plus pembrolizumab dose-escalation and dose-expansion. Part 2 evaluated CMP-001 monotherapy. Accessible lesion(s) were injected intratumorally with CMP-001, at a polysorbate 20 (PS20) concentration of either 0.01% or 0.00167%. The Part 1 primary objective was to identify the recommended phase 2 dose (RP2D) and schedule of CMP-001 plus pembrolizumab, while the Part 2 primary objective was to assess the safety of CMP-001 monotherapy. Secondary objectives for both parts were a preliminary assessment of antitumor activity of CMP-001 plus pembrolizumab and CMP-001 monotherapy, and the overall safety profile and pharmacodynamics of the combination.

Results In Part 1 (N=159) and Part 2 (N=40), 93.1% and 80.0% of patients had PD as their last response to prior anti–PD-1 therapy, respectively. The most common treatment-related adverse events (TRAEs; >25%) were flu-like symptoms (Parts 1 and 2) and injection-site reactions (Part 1). Grade 3/4 TRAEs were reported in 36.5% (Part 1) and 22.5% (Part 2) of patients, the most common being hypotension (Part 1: 6.9%; Part 2: 5.0%). No Grade 5 TRAEs were observed. In Part 1, the best objective response rate (ORR; RECIST v1.1) in patients treated with pembrolizumab and CMP-001 (PS20 0.01%) was 23.5% (23/98), while CMP-001 PS20 (0.00167%) resulted in a lower ORR of 11.5% (7/61). Seven additional patients had a delayed response after initial PD (table 1). The median duration of response was >1 year. In the 37 RECIST v1.1 and post-progression responders, the mean regression in injected and noninjected target lesions was 54.7% and 52.7%, respectively. In Part 2, the best ORR with CMP-001 monotherapy was 17.5% (7/40 patients); the response duration was shorter than in Part 1. Intratumoral CMP-001 PS20 0.01% 10 mg was selected as the RP2D.

Abstract 304 Table 1

Best ORR With CMP-001 Plus Pembrolizumab and CMP-001 Monotherapy

Conclusions Intratumoral CMP-001 was well-tolerated and provided both local and distant responses in patients with advanced melanoma with disease progression on prior PD-1 blockade. CMP-001 monotherapy induced systemic tumor regression in some patients, but duration of response was substantially increased by the addition of pembrolizumab.

Acknowledgements This work was supported by Checkmate Pharmaceuticals. Medical writing assistance was provided by Cindy Rigby, PhD, of ApotheCom (San Francisco, CA) and was funded by Checkmate Pharmaceuticals.

Trial Registration NCT02680184

Ethics Approval This study was approved by the WCG-WIRB, WIRB approval tracking number 20152597.

Consent N/A

References N/A

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