Journal article
Phase 2, Open-Label, Multicenter Study of Nelitolimod in Combination with Pembrolizumab in Anti-PD-1 Treatment-Naive Advanced Melanoma
Clinical cancer research, Vol.31(19), pp.4070-4078
10/01/2025
DOI: 10.1158/1078-0432.CCR-25-0987
PMID: 40711475
Abstract
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-programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) therapy.
Patients with advanced melanoma who were naive to anti-PD-1/PD-L1 therapy received either nelitolimod 2 mg injected into 1-4 lesions or nelitolimod 8 mg injected weekly into a single lesion for 4 weekly doses, then every 3 weeks. Pembrolizumab 200 mg was administered intravenously every 3 weeks.
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. 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 (TEAE) with either drug; overall, 31 patients (37%) had a grade 3 or 4 TEAE related to either study drug.
In patients with anti-PD-1/PD-L1 treatment-naive advanced melanoma, nelitolimod plus pembrolizumab induced objective responses, including in PD-L1-negative tumors. The treatment combination warrants further study in advanced melanoma.
Details
- Title: Subtitle
- Phase 2, Open-Label, Multicenter Study of Nelitolimod in Combination with Pembrolizumab in Anti-PD-1 Treatment-Naive Advanced Melanoma
- Creators
- Antoni Ribas - University of California, Los AngelesMohammed M Milhem - University of Iowa Hospitals and ClinicsChristopher J Hoimes - Duke UniversityAsim Amin - Carolinas Healthcare SystemChristopher D Lao - U-M Rogel Cancer CenterRobert M Conry - Clearview Cancer InstituteJason P Hunt - Huntsman Cancer InstituteGregory A Daniels - UC San Diego Health SystemMohammed Almubarak - West Virginia UniversityMontaser Shaheen - The University of Texas Health Science Center at San AntonioTheresa Medina - University of Colorado Anschutz Medical CampusMinal Barve - Sarah CannonSarwan Bishnoi - Adelaide Cancer Center, Kurralta Park, SA, AustraliaEhtesham Abdi - Griffith UniversityMichael J Chisamore - MerckCristiana Guiducci - Dynavax TechnologiesJose Gomez-Romo - Dynavax TechnologiesAlbert Candia - WoodsideErick Gamelin - C4 TherapeuticsRobert L Coffman - Dynavax TechnologiesRobert S Janssen - Dynavax TechnologiesGeorgina V Long - The University of Sydney
- Resource Type
- Journal article
- Publication Details
- Clinical cancer research, Vol.31(19), pp.4070-4078
- DOI
- 10.1158/1078-0432.CCR-25-0987
- PMID
- 40711475
- NLM abbreviation
- Clin Cancer Res
- ISSN
- 1557-3265
- eISSN
- 1557-3265
- Publisher
- AMER ASSOC CANCER RESEARCH
- Grant note
- Dynavax Technologies CorporationDynavax Technologies Corporation: SD-101 Dynavax Technologies Corporation - Dynavax Technologies Corporation: R35 CA197633 Merck & Co., Inc. - Parker Institute for Cancer Immunotherapy
The authors thank the patients and their families and caregivers for participating in the study; the participating study teams; Elliot Chartash and M.J. Chisamore for input into study design (Merck & Co., Inc.); and Biao Xing, Tripta Dahiya, and Mounika Gujjula for contributing to the analysis of the data (Dynavax Technologies Corporation). Medical writing and editorial support for the preparation of this manuscript, under the guidance of the authors, was provided by Olivia Tamburello, BSc, of ApotheCom. This assistance was funded by Dynavax Technologies Corporation. Dynavax Technologies Corporation, the study sponsor, assisted with study design, data acquisition, statistical analyses, and manuscript development. This study was funded by Dynavax Technologies Corporation, which provided nelitolimod (previously known as SD-101). Merck & Co., Inc., provided pembrolizumab. Antoni Ribas is funded by the Parker Institute for Cancer Immunotherapy and NIH grant R35 CA197633.
- Language
- English
- Electronic publication date
- 07/25/2025
- Date published
- 10/01/2025
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984865436102771
Metrics
3 Record Views