Clinically, 13 patients experienced stable disease, with a median duration of 6.7 months (range, 2.4-13.4 months). Two patients with melanoma had tumor regression (~20% shrinkage in target lesions) and six of eight patients who received immune checkpoint inhibitors within 3 months of vaccination had objective tumor regression.3 Baseline NY-ESO-1 expression did not appear to correlate with clinical response: stable disease was seen in 26% of patients with NY-ESO-1 expression and 33% of those without NY-ESO-1 expression at baseline. However, patients who developed NY-ESO-1–specific T-cell responses after vaccination were more likely to experience stable disease than those who did not (~50% vs. 13%, respectively).3

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Among eight patients who received subsequent treatment with ipilimumab or a TLR agonist, six had at least partial response. All six had confirmed NY-ESO-1 expression at baseline. Five developed cellular immunity to NY-ESO-1 and four developed and maintained humoral immunity to NY-ESO-1 by the end of treatment with CDX-1401. The most frequently reported adverse events were injection site reactions, fatigue, nausea, and chills, and no dose-limiting or grade 3 toxicities were reported.3

“CDX-1401 offers a novel, well-tolerated and practical approach to generating protein-specific immunity that can be readily combined with other treatment strategies to boost immunity against pathogens and tumors,” said lead author Madhav Dhodapkar, MBBS, Arthur H. and Isabel Bunker Professor of Medicine and Immunobiology, and chief of the Section of Hematology at the Department of Internal Medicine and Clinical Research Program Leader of the Hematology Program at Yale Cancer Center. “The preliminary findings in patients who received therapy with a checkpoint inhibitor following the vaccine provide further rationale for combination immunotherapy strategies, meriting further investigation.”

References

  1. Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012;12(4):252-264.
  2. Vanneman M, Dranoff G. Combining immunotherapy and targeted therapies in cancer treatment. Nat Rev Cancer. 2012;12(4):237-251.
  3. Dhodapkar MV, Sznol M, Zhao B, et al. Induction of antigen-specific immunity with a vaccine targeting NY-ESO-1 to the dendritic cell receptor DEC-205. Sci Transl Med. 2014;6(232):232ra51.

Topics:

General Oncology Immunotherapy