Human tumor cells express antigens that serve as targets for the host cellular immune system. This phase 1 dose-escalating study was conducted to assess safety and tolerability of G305, a recombinant NY-ESO-1 protein vaccine mixed with glucopyranosyl lipid A (GLA), a synthetic TLR4 agonist adjuvant, in a stable emulsion (SE). Twelve patients with solid tumors expressing NY-ESO-1 were treated using a 3 + 3 design. The NY-ESO-1 dose was fixed at 250 µg, while GLA-SE was increased from 2 to 10 µg. Safety, immunogenicity, and clinical responses were assessed prior to, during, and at the end of therapy. G305 was safe and immunogenic at all doses. All related AEs were Grade 1 or 2, with injection site soreness as the most commonly reported event (100%). Overall, 75% of patients developed antibody response to NY-ESO-1, including six patients with increased antibody titer ( ≥ 4-fold rise) and three patients with seroconversion from negative (titer < 100) to positive (titer ≥ 100). CD4 T-cell responses were observed in 44.4% of patients; 33.3% were new responses and 1 was boosted ( ≥ 2-fold rise). Following treatment, 8 of 12 patients had stable disease for 3 months or more; at the end of 1 year, three patients had stable disease and nine patients were alive. G305 is a potent immunotherapeutic agent that can stimulate NY-ESO-1-specific antibody and T-cell responses. The vaccine was safe at all doses of GLA-SE (2–10 µg) and showed potential clinical benefit in this population of patients.
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Adverse event of special interest
Common Terminology Criteria for Adverse Events
Eastern Cooperative Oncology Group
Enzyme-linked immunosorbent assay
Enzyme-linked immunospot assay
Glucopyranosyl lipid A
Glucopyranosyl lipid A in stable emulsion
Granulocyte–macrophage colony-stimulating factor
Geometric mean titers
Human leukocyte antigen
Intracellular cytokine staining
Institutional Review Board
Medical Dictionary for Regulatory Activities
Maximum tolerated dose
Myeloid differentiation primary response 88
National Cancer Institute USA
Nuclear factor kappa-light-chain-enhancer of activated B cells
NACHT, LRR and PYD domains-containing protein 3
Non-small cell lung cancer
New York esophageal squamous cell carcinoma 1
Peripheral blood mononuclear cells
Polyinosinic-polycytidylic acid–poly-l-lysine carboxymethylcellulose
Response Evaluation Criteria in Solid Tumors
Serious adverse events
Staphylococcus aureus enterotoxin type B
Safety Monitoring Committee
Treatment emergent adverse events
TIR-domain-containing adapter-inducing interferon-β
Upper limit of normal
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The authors thank the patients and staff at each clinical site, Kevin Tuballes for technical help as part of the Human Immune Monitoring Center at Mount Sinai, and Karen Rappaport for assistance with drafting the manuscript as part of the team at Immune Design.
This research was funded by Immune Design Corp.
Conflict of interest
Hailing Lu, Richard Kenney, and Jan ter Meulen are full-time employees and shareholders of Immune Design Corp. Sacha Gnjatic has received research support from Immune Design Corp. The authors declare that there are no other conflicts of interest.
Ethical approval and ethical standards
This trial is registered in the USA under the ClinicalTrials.gov identifier (NCT number): NCT02015416. Institutional Review Boards (IRBs) reviewed and approved the protocol, all protocol amendments, informed consent documents, and written study materials before their use.
Roswell Park Cancer Institute (sponsor protocol #IDC-G305-2013-001 and RPCI protocol # PH 244813); Scottsdale Healthcare (WIRB Protocol Number: 20131768; WIRB Study Number: 1142287); Karmanos Cancer Institute (WIRB Protocol Number: 20131768; WIRB Study Number: 1143287); H. Lee Moffitt Cancer Ctr & Research Inst, Inc. (sponsor protocol #IDC-G305-2013-001–MCC 17622). The Karmanos Cancer Institute did not identify suitable patients to enroll on the trial.
Human/animal rights statement
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
All patients provided informed consent prior to study enrollment at the screening visit. Patients also agreed on the use of patient data for research and publication.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Note on previous publication: Preliminary data of this study was presented at the 2015 American Society of Clinical Oncology (ASCO) meeting, Chicago, IL, USA, Abstract # 152974 .
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Mahipal, A., Ejadi, S., Gnjatic, S. et al. First-in-human phase 1 dose-escalating trial of G305 in patients with advanced solid tumors expressing NY-ESO-1. Cancer Immunol Immunother 68, 1211–1222 (2019). https://doi.org/10.1007/s00262-019-02331-x
- Solid tumors
- Glucopyranosyl lipid A
- Clinical trial