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A phase I dose escalation trial of MAGE-A3- and HPV16-specific peptide immunomodulatory vaccines in patients with recurrent/metastatic (RM) squamous cell carcinoma of the head and neck (SCCHN)

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Abstract

Background

We conducted a phase I dose escalation study to evaluate the safety and immunologic response to peptide immunomodulatory vaccines GL-0810 (HPV16) and GL-0817 (MAGE-A3) in HPV16 and MAGE-A3-positive RM–SCCHN patients, respectively.

Methods

Three dose levels (500, 1,000, and 1,500 µg) of GL-0810 or GL-0817 with adjuvants Montanide (1.2 ml) and GM-CSF (100 µg/m2) were administered subcutaneously q2 weeks for a total of four vaccinations in HPV16 and MAGE-A3-positive RM–SCCHN patients, respectively.

Results

Nine and seven patients were enrolled in the HPV16 and MAGE-A3 cohorts, respectively. No dose-limiting toxicities were observed, and toxicity was predominantly local and grade 1 (erythema, pain, and itching at the injection site). In those patients who received all four vaccinations, 80 % (4/5) of the HPV16 cohort and 67 % (4/6) of the MAGE-A3 cohort developed antigen-specific T cell and antibody responses to the vaccine. Significant concordance between T cell and antibody responses was observed for both groups. No clear dose–response correlation was seen. All patients progressed by RECIST at first repeat imaging, except for one patient in the MAGE-A3 500 µg cohort who had stable disease for 10.5 months. The median PFS and OS for the MAGE-A3 cohorts were 79 and 183 days, respectively, and for the HPV16 cohort 80 and 196 days, respectively.

Conclusions

GL-0810 and GL-0817 were well tolerated in patients with RM–SCCHN with T cell and antibody responses observed in the majority of patients who received all four vaccinations.

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Abbreviations

B7H1:

B7 homolog 1

CNS:

Central nervous system

CR:

Complete response

CTCAE:

Common toxicity criteria for adverse events

DLT:

Dose-limiting toxicity

ECOG:

Eastern Cooperative Oncology Group

ELISA:

Enzyme-linked immunosorbent assay

ELISPOT:

Enzyme-linked immunospot

GM-CSF:

Granulocyte macrophage colony stimulating factor

HIV:

Human immunodeficiency virus

HLA:

Human leukocyte antigen

HPV16:

Human papillomavirus 16

IFN-γ:

Interferon gamma

IL-10:

Interleukin 10

MAGE:

Melanoma antigen E

MDSC:

Myeloid derived suppressor cells

ml:

Milliliter

m2:

Meter squared

MTD:

Maximum tolerated dose

NSCLC:

Non-small cell lung cancer

OS:

Overall survival

PD:

Progressive disease

PD-1:

Programmed death 1

PD-L1:

Programmed death-ligand 1

PET/CT:

Positron emission tomography–computed tomography

PGE2:

Prostaglandin E2

PR:

Partial response

RECIST:

Response evaluation criteria in solid tumors

R/M:

Recurrent/metastatic

SCCHN:

Squamous cell carcinoma of the head and neck

SD:

Stable disease

TAP:

Transporter associated with antigen processing

TGF-β:

Transforming growth factor beta

Tregs:

Regulatory T cells

UMGCC:

University of Maryland Greenebaum Cancer Center

μg:

Microgram

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Conflict of interest

Dr. Strome is a co-founder and stockholder of Gliknik Inc., a biotechnology company and licensee of the Trojan Peptide Vaccines. Dr. Strome also receives royalties from the Mayo Clinic College of Medicine for intellectual property related to B7-H1 (PD-L1). All other authors have no disclosures.

Author information

Authors and Affiliations

  1. University of Maryland Marlene and Stewart Greenebaum Cancer Center, 22 South Greene St. Rm N9E29, Baltimore, MD, 21201, USA

    Dan P. Zandberg, Olga Goloubeva, Lisa M. Schumaker, Kevin J. Cullen, Ann Zimrin, Robert Ord, Joshua E. Lubek & Martin J. Edelman

  2. Division of Medical Oncology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA

    Dan P. Zandberg, Kevin J. Cullen, Ann Zimrin & Martin J. Edelman

  3. Department of Pathology, University of Maryland School of Medicine, Baltimore, MD, USA

    Sandra Rollins, John C. Papadimitriou & Dean Mann

  4. Department of Radiology, University of Maryland School of Medicine, Baltimore, MD, USA

    Robert E. Morales

  5. Department of Biostatistics, Bioinformatics and Biomathematics, Georgetown Lombardi Comprehensive Cancer Center, washington, DC, USA

    Ming Tan

  6. Department of Otorhinolaryngology-Head and Neck Surgery, University of Maryland, Baltimore, MD, USA

    Rodney Taylor, Jeffrey S. Wolf & Scott E. Strome

  7. Department of Oral and Maxillofacial Surgery, University of Maryland School of Medicine, Baltimore, MD, USA

    Robert Ord & Joshua E. Lubek

  8. Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD, USA

    Mohan Suntharalingam

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  1. Dan P. Zandberg
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  2. Sandra Rollins
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  15. Dean Mann
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  16. Scott E. Strome
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Corresponding author

Correspondence to Dan P. Zandberg.

Additional information

Scott E. Strome and Martin J. Edelman have share senior authorship.

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Zandberg, D.P., Rollins, S., Goloubeva, O. et al. A phase I dose escalation trial of MAGE-A3- and HPV16-specific peptide immunomodulatory vaccines in patients with recurrent/metastatic (RM) squamous cell carcinoma of the head and neck (SCCHN). Cancer Immunol Immunother 64, 367–379 (2015). https://doi.org/10.1007/s00262-014-1640-x

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  • DOI: https://doi.org/10.1007/s00262-014-1640-x

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