SD-101 May Enhance the Effectiveness of Immunotherapy in Melanoma
Immunotherapies with anti-PD-1 agents are novel options for patients with melanoma, but high resistance levels can be a challenge.
Intratumoral SD-101 may enhance the effectiveness of immunotherapy with pembrolizumab without major additional toxicities among patients with advanced melanoma, according to a study published in Cancer Discovery.
Immunotherapies with anti-PD-1 agents such as pembrolizumab and nivolumab are novel options for patients with melanoma, but a major challenge in management are high levels of resistance. Previous studies have suggested that combining immunotherapy with additional immune mediation may improve response rates.
For this phase 1b study, researchers enrolled 22 patients with unresectable or metastatic malignant melanoma and treated them with pembrolizumab and intratumoral SD-101, a synthetic CpG-oligonucleotide that elicits an immune response by stimulating Toll-like receptor 9 (TLR9).
Of the 9 patients who were anti-PD-1/L1 therapy-naive, 7 patients (78%) had a confirmed objective response, including 2 complete responses. Of the 12 evaluable patients previously exposed to immunotherapy, 2 patients had confirmed partial responses; 5 patients had reductions in tumor size, but other than the responding patients, all participants in this group experienced disease progression 1.5 to 8 months after enrollment.
All patients had at least 1 treatment-emergent adverse event (TEAE); most TEAEs were grade 1 to 2 in severity. All patients experienced flu-like symptoms, but symptoms were observed more frequently among patients who received higher doses of SD-101. The most common grade 3 to 4 TEAEs included chills, myalgia, and injection-site pain. Three patients experienced new-onset immune related adverse events.
The authors concluded that the combination “induces favorable changes in the tumor microenvironment with increased type I interferon and CD8 T cell infiltration. These changes may result in a high response rate in combination with pembrolizumab, especially in patients who have not previously received anti-PD-1 therapy and with minimal additional toxicity.”
Ribas A, Medina T, Kummar S, et al. SD-101 in combination with pembrolizumab in advanced melanoma: results of a phase 1b, multicenter study[published online August 28, 2018]. Cancer Discov. doi: 10.1158/2159-8290.CD-18-0280