CHICAGO — Intralesional agent SD-101 plus pembrolizumab induced a high response rate with a tolerable safety profile among a small cohort of patients with metastatic melanoma, according to results of a phase 1b/phase 2 trial presented at ASCO Annual Meeting.
Antoni Ribas, MD, PhD, professor of medicine, surgery, and molecular and medical pharmacology at University of California Los Angeles, and director of the tumor immunology program at Jonsson Comprehensive Cancer Center, and colleagues, assessed whether SD-101 (Dynavax) — a CpG-ODN agonist of TLR9 — could enhance response to pembrolizumab (Keytruda, Merck) among patients with stage IIIc or stage IV melanoma.
“Patients with metastatic melanoma who respond to anti-PD-1 therapy like pembrolizumab have a pre-existing immune response to the cancer that is blocked by PD-1 interacting with PD-L1,” Ribas told HemOnc Today. “In patients where this is not the case, then giving anti-PD-1 therapies will not work.”
In the phase 1b portion of the trial, nine patients received multiple doses of SD-101 injected into a tumor once a week for four cycles, then once every 3 weeks for seven cycles; a fixed 200-mg dose of pembrolizumab was administered every 3 weeks.
Phase 2 includes 54 patients treated with SD-101 in an 8-mg dose in one lesion and 2-mg dose per lesion for two to four lesions beginning 21 days following the first dose pembrolizumab dose.
Median age of patients was 67 years, 67% were men, 27% had stage IV M1a/b disease and 37% had stage IV M1c disease. Seventy percent were treatment naive.
“In this study, we are giving an injection of an agent called SD-101 directly into tumor lesions with the goal of attracting the immune response to the cancer and, at the same time, we block PD-1 with pembrolizumab so this immune response will act in this and other cancer lesions,” Ribas said. “This way, we hope to initiate the antitumor immune response in patients who did not have it started, and expand it throughout the body to fight cancer lesions anywhere.”
SD101 plus pembrolizumab was associated with a 70% antitumor response, according to Ribas. “The clinical response was independent of having a pre-existing immune response in the tumor as this combined therapy effectively increased the intratumoral infiltration by immune cells,” he said.
Nine percent of patients experienced grade 3 or worse treatment-related myalgia, headache and fatigue, while 7% experienced chills and 5% reported malaise. The rate of immune-related events was 17%.
“Administering an agent as SD-101, which is a sequence of nucleic acids that mimics a bacterial infection, can start an antitumor immune response and effectively combine with anti-PD-1 therapy to provide increased responses in patients with metastatic cancer,” Ribas said. “This combination should be tested in randomized clinical trials to demonstrate its potential benefit in larger populations.” – by Rob Volansky
Ribas A, et al. Abstract #9513. Presented at: ASCO Annual Meeting; June 1-5, 2018; Chicago.
Disclosures: Ribas reports stock or ownership interests in Advaxis, Arcus Biosciences, Compugen, CytomX Therapeutics, Five Prime Therapeutics, FLX Bio, PACT Pharma and Tango Therapeutics; and consulting/advisory roles with Amgen, Genentech/Roche, Merck and Novartis. Please see the abstract for all other authors’ relevant financial disclosures.