Clinical StudyA Phase 1 Study of a Vaccine Targeting Preferentially Expressed Antigen in Melanoma and Prostate-specific Membrane Antigen in Patients With Advanced Solid TumorsWeber, Jeffrey S.*; Vogelzang, Nicholas J.†; Ernstoff, Marc S.‡; Goodman, Oscar B.†; Cranmer, Lee D.§; Marshall, John L.∥; Miles, Sabrina¶; Rosario, Dar¶; Diamond, David C.¶; Qiu, Zhiyong¶; Obrocea, Mihail¶; Bot, Adrian¶ Author Information *Department of Cutaneous Oncology, Tampa, FL †Nevada Cancer Institute, Las Vegas, NV ‡Dartmouth-Hitchcock Medical Center, Lebanon, NH §Arizona Cancer Center, Tucson, AZ ∥Lombardi Comprehensive Cancer Center, Georgetown, DC ¶MannKind Corporation, Valencia, CA Sabrina Miles, Dar Rosario, David C. Diamond, Zhiyong Qiu, and Adrian Bot are employees of MannKind Corporation. Mihail Obrocea was an employee of Mannkind Corporation when this study was conducted. All remaining authors have declared that there are no conflicts of interest in regards of this study. Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website, www.immunotherapy-journal.com. Reprints: Jeffrey S. Weber, Department of Cutaneous Oncology, Moffitt Cancer Center, 12902 Magnolia Drive - SRB2, Tampa, FL 33612 (e-mail: [email protected]). Received December 27, 2010 Accepted May 27, 2011 Journal of Immunotherapy 34(7):p 556-567, September 2011. | DOI: 10.1097/CJI.0b013e3182280db1 Buy SDC Metrics Abstract Preferentially expressed antigen in melanoma (PRAME) and prostate-specific membrane antigen (PSMA) are tumor-associated antigens implicated in cellular differentiation, genetic stability, and angiogenesis. MKC1106-PP is an immunotherapeutic regimen cotargeting PRAME and PSMA, comprised of a recombinant plasmid (pPRA-PSM encoding fragments derived from both antigens) and 2 peptides (E-PRA and E-PSM derived from PRAME and PSMA, respectively). This multicenter study evaluated MKC1106-PP with a fixed plasmid dose and 2 different peptide doses, administered by intralymph node injection in a prime-boost sequence in human leukocyte antigen-A*0201 and tumor-antigen-positive patients with progressing metastatic solid tumors who had failed standard therapy. Immune monitoring was done by tetramer and enzymatic-linked immune spot analysis. The treatment was well tolerated, with no significant differences in safety, immune response, and clinical outcome relative to peptide doses. Fifteen of 24 evaluable patients showed an immune response, as defined by the expansion of PRAME-specific or PSMA-specific T cells in the blood. There were no partial or complete responses by the Response Evaluation Criteria in Solid Tumors. Seven patients showed stable disease (SD) for 6 months or longer, or prostate specific antigen decline: 4 of 10 with prostate carcinoma, 2 of 2 with renal clear cell carcinoma, and 1 of 10 with metastatic melanoma. In addition, there was an association between the induction and persistence of antigen-specific T cells in blood above baseline levels and disease control, defined as SD for 6 months or longer. These results support further development of MKC1106-PP in specific clinical indications. © 2011 Lippincott Williams & Wilkins, Inc.