Phase 2, Open-Label, Multicenter Study of Nelitolimod in Combination with Pembrolizumab in Anti-PD-1 Treatment-Naïve Advanced Melanoma

  • Clin Cancer Res. 2025 Oct 1;31(19):4070-4078. doi: 10.1158/1078-0432.CCR-25-0987.
Antoni Ribas  1 ,  Mohammed M Milhem  2 ,  Christopher J Hoimes  3 ,  Asim Amin  4 ,  Christopher D Lao  5 ,  Robert M Conry  6 ,  Jason P Hunt  7 ,  Gregory A Daniels  8 ,  Mohammed Almubarak  9 ,  Montaser Shaheen  10 ,  Theresa Medina  11 ,  Minal Barve  12 ,  Sarwan Bishnoi  13 ,  Ehtesham Abdi  14  15 ,  Michael J Chisamore  16 ,  Cristiana Guiducci  17 ,  Jose Gomez-Romo  18 ,  Albert Candia  19 ,  Erick Gamelin  20 ,  Robert L Coffman  21 ,  Robert S Janssen  21 ,  Georgina V Long  22  23  24  25
Affiliations
  • 1. Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, California.
  • 2. Department of Internal Medicine, University of Iowa Health Care, Iowa City, Iowa.
  • 3. Duke Cancer Institute, Duke University, Durham, North Carolina.
  • 4. Department of Solid Tumor and Investigational Therapeutics, Atrium Health Levine Cancer Institute, Wake Forest University School of Medicine, Charlotte, North Carolina.
  • 5. Rogel Cancer Center, University of Michigan, Ann Arbor, Michigan.
  • 6. School of Medicine, University of Alabama, Birmingham, Alabama.
  • 7. Department of Otolaryngology, University of Utah School of Medicine, Huntsman Cancer Institute, Salt Lake City, Utah.
  • 8. UC San Diego Health, University of California, La Jolla, California.
  • 9. Mary Babb Randolph Cancer Center, West Virginia University, Morgantown, West Virginia.
  • 10. The University of Texas Health Science Center at San Antonio, UT Health San Antonio, San Antonio, Texas.
  • 11. School of Medicine, University of Colorado Cancer Center, Aurora, Colorado.
  • 12. Mary Crowley Cancer Research, Sarah Cannon Research Institute, Dallas, Texas.
  • 13. Adelaide Cancer Center, Kurralta Park, Australia.
  • 14. Tweeds Valley Hospital, Cudgen, Australia.
  • 15. School of Medicine, Griffith University, Gold Coast, Australia.
  • 16. Merck & Co., Inc., Rahway, New Jersey.
  • 17. Rezo Therapeutics, San Francisco, California.
  • 18. University of California, San Francisco, San Francisco, California.
  • 19. IGM Biosciences, Mountain View, California.
  • 20. Acrivon Therapeutics, Watertown, Massachusetts.
  • 21. Dynavax Technologies Corporation, Emeryville, California.
  • 22. Melanoma Institute Australia, Sydney, Australia.
  • 23. Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.
  • 24. Department of Medical Oncology, Royal North Shore Hospital, Sydney, Australia.
  • 25. Mater Hospital, Sydney, Australia.
PMID: 40711475 DOI: 10.1158/1078-0432.CCR-25-0987
Abstract

Purpose: Nelitolimod (previously SD-101) is a Toll-like Receptor 9 agonist. We assessed whether intratumoral nelitolimod plus pembrolizumab potentiates antitumor activity in patients with advanced Melanoma who had not previously received anti-PD-1/PD-L1 therapy.

Patients and methods: Patients with advanced Melanoma who were naïve to anti-PD-1/PD-L1 therapy received either nelitolimod 2 mg injected into 1 to 4 lesions or nelitolimod 8 mg injected weekly into a single lesion for 4 weekly doses and then every 3 weeks. Pembrolizumab 200 mg was administered intravenously every 3 weeks.

Results: Forty-five patients received nelitolimod 2 mg and 41 patients received nelitolimod 8 mg per injection. The objective response rate (ORR) was 76% in the 2-mg group and 49% in the 8-mg group. In those with distant metastases, ORRs in both treatment groups were similar to the overall ORRs. In the 2-mg group, treatment responses were similar in those with PD-L1-positive Tumors and those with PD-L1-negative Tumors. The progression-free survival rate at 18 months (landmark) was 62% in the 2-mg group and 40% in the 8-mg group. Forty-four patients (100%) in the 2-mg group and 37 patients (95%) in the 8-mg group experienced a treatment-related adverse event with either drug; overall, 31 patients (37%) had a grade 3 or 4 treatment-related adverse event related to either study drug.

Conclusions: In patients with anti-PD-1/PD-L1 treatment-naïve advanced Melanoma, nelitolimod plus pembrolizumab induced objective responses, including in PD-L1-negative Tumors. The treatment combination warrants further study in advanced Melanoma.

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