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First-in-human phase 1 dose-escalating trial of G305 in patients with advanced solid tumors expressing NY-ESO-1


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


Adverse event of special interest


Alkaline phosphatase


Bacillus Calmette–Guerin


Cytosine phosphate–guanine


Computed tomography


Common Terminology Criteria for Adverse Events


Dose-limiting toxicity


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


Lactate dehydrogenase


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


Standard deviation


Stable emulsion


Staphylococcus aureus enterotoxin type B


Safety Monitoring Committee


Tumor-associated antigens


Treatment emergent adverse events


Toll-like receptor


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.

Author information




Trial conception and design: AM, SE, RK, KO. Acquisition of data: AM, SE, SG, SK-S, HL, RK, KO. Analysis and interpretation of data: AM, SE, SG, HL, JM, RK, KO. Writing, review, and/or revision of the manuscript: AM, RK, JM. Study supervision: AM, SE, RK, KO.

Corresponding author

Correspondence to Jan H. ter Meulen.

Ethics declarations

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 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.

Institutional approvals

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.

Informed consent

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.

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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 [1].

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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).

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  • NY-ESO-1
  • Solid tumors
  • Vaccine
  • Glucopyranosyl lipid A
  • Clinical trial