HLA-restricted NY-ESO-1 peptide immunotherapy for metastatic castration resistant prostate cancer

• Published in: Investigational new drugs 2014-04, Vol.32 (2), p.235-242
• Main Authors: Sonpavde, Guru, Wang, Mingjun, Peterson, Leif E., Wang, Helen Y., Joe, Teresa, Mims, Martha P., Kadmon, Dov, Ittmann, Michael M., Wheeler, Thomas M., Gee, Adrian P., Wang, Rong-Fu, Hayes, Teresa G.
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Antigens; Antigens, Neoplasm - immunology; Antineoplastic agents; Biological and medical sciences; Cancer therapies; Cancer Vaccines; Clinical trials; Drug dosages; Gynecology. Andrology. Obstetrics; Haplotypes; Heart attacks; Hepatitis; Histocompatibility Antigens Class I - immunology; Histocompatibility Antigens Class II - immunology; HLA Antigens; Humans; Immunotherapy; Leukocytes, Mononuclear - immunology; Male; Male genital diseases; Medical schools; Medical sciences; Medicine; Medicine & Public Health; Melanoma; Membrane Proteins - immunology; Metastasis; Middle Aged; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Nephrology. Urinary tract diseases; Oncology; Patients; Peptides; Peptides - therapeutic use; Pharmaceutical sciences; Pharmacology. Drug treatments; Pharmacology/Toxicology; Phase I Studies; Prostate cancer; Prostatic Neoplasms, Castration-Resistant - immunology; Prostatic Neoplasms, Castration-Resistant - therapy; Studies; T-Lymphocytes - immunology; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland; Vaccines
• ISSN: 0167-6997; 1573-0646
• DOI: 10.1007/s10637-013-9960-9

Summary Background Given the immunogenicity of NY-ESO-1 peptides in prostate cancer, a phase I clinical trial was designed to evaluate HLA class-I and class-II restricted NY-ESO-1 peptides in metastatic castration-resistant prostate cancer (mCRPC). Methods Patients with progressive mCRPC, Zubrod Performance Status ≤2, PSA ≥10 ng/ml who had appropriate HLA class I (A2) and class II haplotypes (DR4, DP4) were eligible. Three groups with 3 patients each received the vaccine subcutaneously every 2 weeks for 6 doses. Group 1 received a peptide presented by an HLA class I haplotype (HLA-A2), Group 2 with a peptide presented by HLA class II haplotype (DR4, DP4), and Group 3 with peptides presented by both Class I and II haplotypes. Androgen-deprivation was continued. Owing to a myocardial infarction, the protocol was amended to omit the use of GM-CSF. Results Fourteen patients were evaluable for toxicities and 9 received all 6 doses and were evaluable for efficacy. One death from myocardial infarction following GM-CSF occurred in a patient with generalized myalgias. After omitting GM-CSF, no grade >2 toxicities were observed. Among 9 patients evaluable for efficacy, the median PSA doubling time pre-therapy and during therapy were 3.1 and 4.92 months, respectively. NY-ESO-1 specific T-cell response observed by ELISPOT appeared more frequent in docetaxel-naïve patients (4 of 4) than docetaxel-pretreated patients (2 of 5). Conclusion In men with mCRPC, individualized HLA class-I and/or class-II restricted NY-ESO-1 peptides were tolerable, appeared to slow PSA doubling time and yielded antigen-specific T-cell responses more often in chemonaïve patients.