Sara M. Tolaney, MD, MPH
Sara M. Tolaney, MD, MPH, Assistant Professor of Medicine at Harvard Medical School and Associate Director of the Susan F. Smith Center for Women’s Cancers at Dana-Farber/Brigham and Women’s Cancer Center, Boston, commented on KEYNOTE-890.
“Previous work has suggested minimal activity of checkpoint inhibitor monotherapy among patients with metastatic triple-negative breast cancer, with response rates ranging from 5% to 10%. Additionally, we have data that adding checkpoint inhibition to chemotherapy improves overall survival among patients with metastatic triple-negative breast cancer that is [programmed cell death ligand 1 (PD-L1)]-positive. This, however, leaves us with an area of unmet need for those patients with PD-L1–negative triple-negative disease,” she said.
“KEYNOTE-890, presented by Telli et al, demonstrates a promising signal for activity of intratumoral administration of a plasmid encoding interleukin-12 [tavokinogene telseplasmid] in combination with pembrolizumab, with an objective response rate of 29% among the 14 patients in the study with evaluable metastatic triple-negative disease. Additionally, work looking at peripheral immune subsets found upregulation of antigen presentation and interferon-gamma signaling,” Dr. Tolaney said.
“It is very interesting that three of the four responders in this study had tumors lacking PD-L1 expression,” she commented. “While this is a small signal-finding study, [tavokinogene telseplasmid] with pembrolizumab may be a possible combination that leads to benefit of immunotherapy even among those patients with PD-L1–negative disease. These data are very encouraging and are supportive of further work being done for patients with metastatic triple-negative disease.”
DISCLOSURE: Dr. Tolaney has served in a consulting or advisory role for AbbVie, AstraZeneca, Bristol-Myers Squibb, Celldex, Eisai, G1 Therapeutics, Genentech, Immunomedics, Lilly, Merck, NanoString Technologies, Nektar, Novartis, Odonate Therapeutics, Paxman, Pfizer, Puma Biotechnology, Sanofi, Seattle Genetics, and Silverback Therapeutics; has received institutional research funding from AstraZeneca, Bristol-Myers Squibb, Cyclacel, Eisai, Exelixis, Genentech/Roche, Immunomedics, Lilly, Merck, NanoString Technologies, Nektar, Novartis, Odonate Therapeutics, and Pfizer; and has been reimbursed for travel, accommodations, or other expenses by AstraZeneca, Celldex, Eisai, Genentech/Roche, Immunomedics, Lilly, Merck, NanoString Technologies, Nektar, Novartis, Pfizer, and Puma Biotechnology.
The phase II KEYNOTE-890 trial is a small but interesting study in patients with inoperable advanced triple-negative breast cancer. After one injection of intratumoral tavokinogene telseplasmid, a plasmid encoding the proinflammatory cytokine interleukin-12 (IL-12), followed by electroporation and...