| Title: |
Intratumoral or Subcutaneous MK-2118, a Noncyclic Dinucleotide STING Agonist, with or without Pembrolizumab, for Advanced or Metastatic Solid Tumors or Lymphomas |
| Authors: |
Luke, Jason J; Sweis, Randy F; Hecht, J Randolph; Schneider, Reva; Stein, Mark N; Golan, Talia; Yap, Timothy A; Khilnani, Anuradha; Huang, Mo; Zhao, Runchen; Jemielita, Thomas; Patel, Sandip Pravin |
| Source: |
Clinical Cancer Research, vol 31, iss 7 |
| Publisher Information: |
eScholarship, University of California |
| Publication Year: |
2025 |
| Collection: |
University of California: eScholarship |
| Subject Terms: |
32 Biomedical and Clinical Sciences (for-2020); 3202 Clinical Sciences (for-2020); 3211 Oncology and Carcinogenesis (for-2020); Immunotherapy (rcdc); Clinical Research (rcdc); Clinical Trials and Supportive Activities (rcdc); Cancer (rcdc); 6.1 Pharmaceuticals (hrcs-rac); Humans (mesh); Antibodies; Monoclonal; Humanized (mesh); Female (mesh); Male (mesh); Middle Aged (mesh); Aged (mesh); Lymphoma (mesh); Adult (mesh); Neoplasms (mesh); Antineoplastic Combined Chemotherapy Protocols (mesh); Membrane Proteins (mesh); Aged; 80 and over (mesh); Injections; Subcutaneous (mesh); Treatment Outcome (mesh) |
| Time: |
1233 - 1242 |
| Description: |
PURPOSE: We evaluated the noncyclic dinucleotide stimulator of IFN genes agonist MK-2118 ± pembrolizumab in participants with advanced solid tumors or lymphomas. PATIENTS AND METHODS: This first-in-human study (NCT03249792) enrolled participants with refractory, advanced solid tumors or lymphomas. Participants received intratumoral (IT) MK-2118 100 to 20,000 μg (arm 1), IT MK-2118 900 to 15,000 μg plus intravenous (IV) pembrolizumab 200 mg every 3 weeks (arm 2), or subcutaneous (SC) MK-2118 5,000 to 150,000 μg plus IV pembrolizumab 200 mg every 3 weeks (arm 4); arm 3 (visceral injection of MK-2118) was not pursued. IT dosing used an accelerated titration design and modified toxicity probability interval method; SC dosing (arm 4) was started subsequent to arms 1 and 2. The primary objectives were safety/tolerability. MK-2118 pharmacokinetics was a secondary endpoint; objective responses and biomarkers were exploratory endpoints. RESULTS: A total of 140 participants were enrolled (arm 1, n = 27; arm 2, n = 57; arm 4, n = 56). Grade 3/4 treatment-related adverse events occurred in 22%, 23%, and 11% of participants, respectively, but no maximum tolerated dose was identified up to MK-2118 20,000, 15,000, and 150,000 μg across the three arms. Dose-dependent increases in MK-2118 systemic exposure were observed following IT and subcutaneous administration. Objective responses were seen in 0%, 6%, and 4% of participants, respectively. IT MK-2118 led to dose-dependent changes in stimulator of interferon genes-based blood RNA expression levels, IFNγ, IFNγ-induced protein 10, and IL6; SC MK-2118 did not generate dose-related immune responses. CONCLUSIONS: IT MK-2118 ± pembrolizumab and SC MK-2118 plus pembrolizumab had manageable toxicity and limited antitumor activity. IT but not SC administration demonstrated systemic immune effects. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
unknown |
| Relation: |
qt4f12c6pr; https://escholarship.org/uc/item/4f12c6pr; https://escholarship.org/content/qt4f12c6pr/qt4f12c6pr.pdf |
| DOI: |
10.1158/1078-0432.ccr-24-2824 |
| Availability: |
https://escholarship.org/uc/item/4f12c6pr; https://escholarship.org/content/qt4f12c6pr/qt4f12c6pr.pdf; https://doi.org/10.1158/1078-0432.ccr-24-2824 |
| Rights: |
CC-BY |
| Accession Number: |
edsbas.4791D57C |
| Database: |
BASE |