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

Amit Mahipal, Samuel Ejadi, Sacha Gnjatic, Seunghee Kim-Schulze, Hailing Lu, Jan H. ter Meulen, Richard Kenney, Kunle Odunsi

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
JournalCancer Immunology, Immunotherapy
DOIs
StatePublished - Jan 1 2019

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Neoplasms
Emulsions
Vaccines
T-Lymphocytes
Safety
Antibodies
Antibody Formation
Immune System
Antigens
Injections
Therapeutics
Population
glucopyranosyl lipid-A
Proteins

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research

Cite this

First-in-human phase 1 dose-escalating trial of G305 in patients with advanced solid tumors expressing NY-ESO-1. / Mahipal, Amit; Ejadi, Samuel; Gnjatic, Sacha; Kim-Schulze, Seunghee; Lu, Hailing; ter Meulen, Jan H.; Kenney, Richard; Odunsi, Kunle.

In: Cancer Immunology, Immunotherapy, 01.01.2019.

Research output: Contribution to journalArticle

Mahipal, Amit ; Ejadi, Samuel ; Gnjatic, Sacha ; Kim-Schulze, Seunghee ; Lu, Hailing ; ter Meulen, Jan H. ; Kenney, Richard ; Odunsi, Kunle. / First-in-human phase 1 dose-escalating trial of G305 in patients with advanced solid tumors expressing NY-ESO-1. In: Cancer Immunology, Immunotherapy. 2019.
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abstract = "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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AU - Lu, Hailing

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