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950 Final analysis: phase 1b study investigating intratumoral injection of toll-like receptor 9 agonist vidutolimod ± pembrolizumab in patients with PD-1 blockade–refractory melanoma
  1. John Kirkwood1,
  2. Yousef Zakharia2,
  3. Diwakar Davar1,
  4. Elizabeth Buchbinder3,
  5. Theresa Medina4,
  6. Adil Daud5,
  7. Antoni Ribas6,
  8. Bartosz Chmielowski6,
  9. Jiaxin Niu7,
  10. Geoffrey Gibney8,
  11. Kim Margolin9,
  12. Anthony Olszanski10,
  13. Inderjit Mehmi11,
  14. Takami Sato12,
  15. Montaser Shaheen13,
  16. Luping Zhao14,
  17. Hong Liu14,
  18. Heather Kelley14,
  19. George Weiner2,
  20. Jason Luke1,
  21. Dmitri Bobilev14,
  22. Arthur Krieg14,
  23. James Wooldridge14 and
  24. Mohammed Milhem2
  1. 1University of Pittsburgh Medical Center, Pittsburgh, PA, USA
  2. 2University of Iowa, Iowa City, IA, 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 Center, Washington, DC, USA
  9. 9City of Hope, Duarte, CA, USA
  10. 10Fox Chase Cancer Center, Philadelphia, PA, USA
  11. 11The Angeles Clinic and Research Institute, 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


Background There are limited therapeutic options for patients with progressive disease (PD) on or after PD-1–blocking antibody therapy. Vidutolimod (CMP-001) is a first-in-class, immunostimulatory virus-like particle containing a CpG-A Toll-like receptor 9 (TLR9) agonist. This phase 1b study evaluated the safety and clinical activity of intratumoral vidutolimod with and without pembrolizumab in patients with refractory melanoma.

Methods This two-part, open-label, multicenter, phase 1b study (NCT02680184) enrolled adults with histologically confirmed metastatic or unresectable cutaneous melanoma who had stable disease after ≥12 weeks or PD on anti−PD-1 treatment, measurable disease per RECIST v1.1, ECOG PS 0/1, and ≥1 lesion accessible for intratumoral injection. Part 1 evaluated vidutolimod + pembrolizumab and Part 2 evaluated vidutolimod monotherapy. Key objectives included assessment of safety and clinical activity, and exploratory analyses were performed on available tumor biopsies using immunohistochemistry and RNAseq.

Results At data cutoff (August 17, 2021), 159 patients had enrolled in Part 1 and 40 patients in Part 2. The median age was 64 years in Part 1 (range, 30-90) and 68 years in Part 2 (range, 30-89). Most patients had PD as their last response to prior anti–PD-1 therapy (Part 1, 93.1%; Part 2, 80.0%). Grade 3/4 treatment-related adverse events (TRAEs) occurred in 37.1% of patients treated with vidutolimod + pembrolizumab and in 22.5% of patients treated with vidutolimod monotherapy. No treatment-related deaths occurred. Based on the efficacy data presented in Table 1, vidutolimod polysorbate 20 (PS20) A was selected for further development as this formulation in combination with pembrolizumab had a best objective response rate (ORR; RECIST v1.1) of 23.5%, with a median duration of response (DOR) of 25.2 months. Vidutolimod monotherapy had an ORR of 20.0%, with a median DOR of 5.6 months. Exploratory translational analyses identified association of unique biomarkers with response among patients with T cell–inflamed versus non-T cell–inflamed tumors at baseline.

Abstract 950 Table 1

Safety and clinical activity of vidutolomod ± pembrolizumab

Conclusions Promising clinical activity was observed with vidutolimod + pembrolizumab and vidutolimod monotherapy in patients with PD-1 blockade–refractory melanoma. A manageable safety profile was observed. The DOR with vidutolimod + pembrolizumab was substantially longer than with vidutolimod monotherapy. Clinical studies to confirm the efficacy of vidutolimod + PD-1 blockade in patients with previously untreated unresectable/metastatic melanoma (phase 2/3, NCT04695977) or PD-1 blockade–refractory melanoma (phase 2, NCT04698187) are ongoing.

Acknowledgements This work was supported by Checkmate Pharmaceuticals. Medical writing assistance was provided by Steffen Biechele, PhD (ApotheCom, San Francisco, CA, USA), and funded by Checkmate Pharmaceuticals.

Trial Registration NCT02680184

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

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