A phase i study of IMP321 and gemcitabine as the front-line therapy in patients with advanced pancreatic adenocarcinoma

Andrea Wang-Gillam, Stacey Plambeck-Suess, Peter Goedegebuure, Peter O. Simon, Jonathan B. Mitchem, John R. Hornick, Steven Sorscher, Joel Picus, Rama Suresh, Albert Lockhart, Benjamin Tan, Williams G. Hawkins

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Purpose This phase I study was conducted to determine the safety profile and maximum tolerated dose (MTD) of IMP321, a soluble lymphocyte activation gene-3 (LAG-3) Ig fusion protein and MHC Class II agonist, combined with gemcitabine in patients with advanced pancreatic adenocarcinoma. Patients and methods Patients with advanced pancreatic adenocarcinoma were treated with gemcitabine (1,000 mg/m2)(level 1), gemcitabine (1,000 mg/m 2) plus IMP 321 at 0.5 mg (level 2) and 2.0 mg (level 3), respectively. Safety, toxicity, and immunological markers at baseline and post treatment were assessed. Results A total of 18 patients were enrolled to the study, and 17 were evaluable for toxicity. None of the 6 patients who received 0.5 mg IMP321 experienced IMP321-related adverse events. Of the 5 patients who received IMP321 at the 2 mg dose level, 1 experienced rash, 1 reported hot flashes and 2 had mild pain at the injection sites. No severe adverse events previously attributed to IMP321 were observed. No significant differences were observed when comparing pre- and post-treatment levels of monocytes (CD11b+CD14+), conventional dendritic cells (CD11c+) or T cell subsets (CD4, CD8). Conclusions IMP321 in combination with gemcitabine is a well-tolerated regimen. IMP321 did not result in any severe adverse events. No incremental activity observed for the additional IMP 321 to gemcitabine at the dose levels evaluated, likely due to sub-optimal dosing. Immunological markers suggested that higher dose levels of IMP321 are needed for future clinical studies.

Original languageEnglish (US)
Pages (from-to)707-713
Number of pages7
JournalInvestigational New Drugs
Volume31
Issue number3
DOIs
StatePublished - Jun 1 2013
Externally publishedYes

Fingerprint

gemcitabine
Adenocarcinoma
Inosine Monophosphate
Therapeutics
Hot Flashes
Safety
Immunoglobulin Genes
Maximum Tolerated Dose
CD223 antigen
T-Lymphocyte Subsets
Lymphocyte Activation
Exanthema
Dendritic Cells
Monocytes

Keywords

  • Chemo-immunotherapy
  • Front-line therapy
  • IMP321
  • LAG-3
  • Pancreatic adenocarcinoma

ASJC Scopus subject areas

  • Oncology
  • Pharmacology
  • Pharmacology (medical)

Cite this

Wang-Gillam, A., Plambeck-Suess, S., Goedegebuure, P., Simon, P. O., Mitchem, J. B., Hornick, J. R., ... Hawkins, W. G. (2013). A phase i study of IMP321 and gemcitabine as the front-line therapy in patients with advanced pancreatic adenocarcinoma. Investigational New Drugs, 31(3), 707-713. https://doi.org/10.1007/s10637-012-9866-y

A phase i study of IMP321 and gemcitabine as the front-line therapy in patients with advanced pancreatic adenocarcinoma. / Wang-Gillam, Andrea; Plambeck-Suess, Stacey; Goedegebuure, Peter; Simon, Peter O.; Mitchem, Jonathan B.; Hornick, John R.; Sorscher, Steven; Picus, Joel; Suresh, Rama; Lockhart, Albert; Tan, Benjamin; Hawkins, Williams G.

In: Investigational New Drugs, Vol. 31, No. 3, 01.06.2013, p. 707-713.

Research output: Contribution to journalArticle

Wang-Gillam, A, Plambeck-Suess, S, Goedegebuure, P, Simon, PO, Mitchem, JB, Hornick, JR, Sorscher, S, Picus, J, Suresh, R, Lockhart, A, Tan, B & Hawkins, WG 2013, 'A phase i study of IMP321 and gemcitabine as the front-line therapy in patients with advanced pancreatic adenocarcinoma', Investigational New Drugs, vol. 31, no. 3, pp. 707-713. https://doi.org/10.1007/s10637-012-9866-y
Wang-Gillam, Andrea ; Plambeck-Suess, Stacey ; Goedegebuure, Peter ; Simon, Peter O. ; Mitchem, Jonathan B. ; Hornick, John R. ; Sorscher, Steven ; Picus, Joel ; Suresh, Rama ; Lockhart, Albert ; Tan, Benjamin ; Hawkins, Williams G. / A phase i study of IMP321 and gemcitabine as the front-line therapy in patients with advanced pancreatic adenocarcinoma. In: Investigational New Drugs. 2013 ; Vol. 31, No. 3. pp. 707-713.
@article{e92139bc5c0346f8abed1c4d1fc31b1d,
title = "A phase i study of IMP321 and gemcitabine as the front-line therapy in patients with advanced pancreatic adenocarcinoma",
abstract = "Purpose This phase I study was conducted to determine the safety profile and maximum tolerated dose (MTD) of IMP321, a soluble lymphocyte activation gene-3 (LAG-3) Ig fusion protein and MHC Class II agonist, combined with gemcitabine in patients with advanced pancreatic adenocarcinoma. Patients and methods Patients with advanced pancreatic adenocarcinoma were treated with gemcitabine (1,000 mg/m2)(level 1), gemcitabine (1,000 mg/m 2) plus IMP 321 at 0.5 mg (level 2) and 2.0 mg (level 3), respectively. Safety, toxicity, and immunological markers at baseline and post treatment were assessed. Results A total of 18 patients were enrolled to the study, and 17 were evaluable for toxicity. None of the 6 patients who received 0.5 mg IMP321 experienced IMP321-related adverse events. Of the 5 patients who received IMP321 at the 2 mg dose level, 1 experienced rash, 1 reported hot flashes and 2 had mild pain at the injection sites. No severe adverse events previously attributed to IMP321 were observed. No significant differences were observed when comparing pre- and post-treatment levels of monocytes (CD11b+CD14+), conventional dendritic cells (CD11c+) or T cell subsets (CD4, CD8). Conclusions IMP321 in combination with gemcitabine is a well-tolerated regimen. IMP321 did not result in any severe adverse events. No incremental activity observed for the additional IMP 321 to gemcitabine at the dose levels evaluated, likely due to sub-optimal dosing. Immunological markers suggested that higher dose levels of IMP321 are needed for future clinical studies.",
keywords = "Chemo-immunotherapy, Front-line therapy, IMP321, LAG-3, Pancreatic adenocarcinoma",
author = "Andrea Wang-Gillam and Stacey Plambeck-Suess and Peter Goedegebuure and Simon, {Peter O.} and Mitchem, {Jonathan B.} and Hornick, {John R.} and Steven Sorscher and Joel Picus and Rama Suresh and Albert Lockhart and Benjamin Tan and Hawkins, {Williams G.}",
year = "2013",
month = "6",
day = "1",
doi = "10.1007/s10637-012-9866-y",
language = "English (US)",
volume = "31",
pages = "707--713",
journal = "Investigational New Drugs",
issn = "0167-6997",
publisher = "Kluwer Academic Publishers",
number = "3",

}

TY - JOUR

T1 - A phase i study of IMP321 and gemcitabine as the front-line therapy in patients with advanced pancreatic adenocarcinoma

AU - Wang-Gillam, Andrea

AU - Plambeck-Suess, Stacey

AU - Goedegebuure, Peter

AU - Simon, Peter O.

AU - Mitchem, Jonathan B.

AU - Hornick, John R.

AU - Sorscher, Steven

AU - Picus, Joel

AU - Suresh, Rama

AU - Lockhart, Albert

AU - Tan, Benjamin

AU - Hawkins, Williams G.

PY - 2013/6/1

Y1 - 2013/6/1

N2 - Purpose This phase I study was conducted to determine the safety profile and maximum tolerated dose (MTD) of IMP321, a soluble lymphocyte activation gene-3 (LAG-3) Ig fusion protein and MHC Class II agonist, combined with gemcitabine in patients with advanced pancreatic adenocarcinoma. Patients and methods Patients with advanced pancreatic adenocarcinoma were treated with gemcitabine (1,000 mg/m2)(level 1), gemcitabine (1,000 mg/m 2) plus IMP 321 at 0.5 mg (level 2) and 2.0 mg (level 3), respectively. Safety, toxicity, and immunological markers at baseline and post treatment were assessed. Results A total of 18 patients were enrolled to the study, and 17 were evaluable for toxicity. None of the 6 patients who received 0.5 mg IMP321 experienced IMP321-related adverse events. Of the 5 patients who received IMP321 at the 2 mg dose level, 1 experienced rash, 1 reported hot flashes and 2 had mild pain at the injection sites. No severe adverse events previously attributed to IMP321 were observed. No significant differences were observed when comparing pre- and post-treatment levels of monocytes (CD11b+CD14+), conventional dendritic cells (CD11c+) or T cell subsets (CD4, CD8). Conclusions IMP321 in combination with gemcitabine is a well-tolerated regimen. IMP321 did not result in any severe adverse events. No incremental activity observed for the additional IMP 321 to gemcitabine at the dose levels evaluated, likely due to sub-optimal dosing. Immunological markers suggested that higher dose levels of IMP321 are needed for future clinical studies.

AB - Purpose This phase I study was conducted to determine the safety profile and maximum tolerated dose (MTD) of IMP321, a soluble lymphocyte activation gene-3 (LAG-3) Ig fusion protein and MHC Class II agonist, combined with gemcitabine in patients with advanced pancreatic adenocarcinoma. Patients and methods Patients with advanced pancreatic adenocarcinoma were treated with gemcitabine (1,000 mg/m2)(level 1), gemcitabine (1,000 mg/m 2) plus IMP 321 at 0.5 mg (level 2) and 2.0 mg (level 3), respectively. Safety, toxicity, and immunological markers at baseline and post treatment were assessed. Results A total of 18 patients were enrolled to the study, and 17 were evaluable for toxicity. None of the 6 patients who received 0.5 mg IMP321 experienced IMP321-related adverse events. Of the 5 patients who received IMP321 at the 2 mg dose level, 1 experienced rash, 1 reported hot flashes and 2 had mild pain at the injection sites. No severe adverse events previously attributed to IMP321 were observed. No significant differences were observed when comparing pre- and post-treatment levels of monocytes (CD11b+CD14+), conventional dendritic cells (CD11c+) or T cell subsets (CD4, CD8). Conclusions IMP321 in combination with gemcitabine is a well-tolerated regimen. IMP321 did not result in any severe adverse events. No incremental activity observed for the additional IMP 321 to gemcitabine at the dose levels evaluated, likely due to sub-optimal dosing. Immunological markers suggested that higher dose levels of IMP321 are needed for future clinical studies.

KW - Chemo-immunotherapy

KW - Front-line therapy

KW - IMP321

KW - LAG-3

KW - Pancreatic adenocarcinoma

UR - http://www.scopus.com/inward/record.url?scp=84879085032&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84879085032&partnerID=8YFLogxK

U2 - 10.1007/s10637-012-9866-y

DO - 10.1007/s10637-012-9866-y

M3 - Article

C2 - 22864469

AN - SCOPUS:84879085032

VL - 31

SP - 707

EP - 713

JO - Investigational New Drugs

JF - Investigational New Drugs

SN - 0167-6997

IS - 3

ER -