A Phase II Study of Allogeneic GM-CSF-Transfected Pancreatic Tumor Vaccine (GVAX) with Ipilimumab as Maintenance Treatment for Metastatic Pancreatic Cancer.

Abstract

PURPOSE:

This phase II study tested granulocyte-macrophage colony-stimulating factor (GM-CSF)-allogeneic pancreatic tumor cells (GVAX) and ipilimumab in metastatic pancreatic ductal adenocarcinoma (PDA) in the maintenance setting.

PATIENTS AND METHODS:

Patients with PDA who were treated with front-line chemotherapy consisting of 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) in the metastatic setting and had ongoing response or stable disease after 8-12 doses were eligible. Patients were randomized 1:1 to treatment with GVAX and ipilimumab given every 3 weeks for four doses then every 8 weeks (Arm A) or to FOLFIRINOX continuation (Arm B). The primary objective was to compare overall survival (OS) between the two arms.

RESULTS:

Eighty-two patients were included in the final analysis (Arm A: 40; Arm B: 42). The study was stopped for futility after interim analysis. Median OS was 9.38 months [95% confidence interval (CI), 5.0-12.2] for Arm A and 14.7 months (95% CI, 11.6-20.0) for Arm B (HR, 1.75; P = 0.019). Using immune-related response criteria, two partial responses (5.7%) were observed in Arm A and four (13.8%) in Arm B. GVAX + ipilimumab promoted T-cell differentiation into effector memory phenotypes both in the periphery and in the tumor microenvironment and increased M1 macrophages in the tumor.

CONCLUSIONS:

GVAX and ipilimumab maintenance therapy did not improve OS over continuation of chemotherapy and resulted in a numerically inferior survival in metastatic PDA. However, clinical responses and biological effects on immune cells were observed. Further study of novel combinations in the maintenance treatment of metastatic PDA is feasible.

• Authors: Annie A Wu, Katherine M Bever, Won Jin Ho, Elana J Fertig, Nan Niu, Lei Zheng, Rose M Parkinson, Jennifer N Durham, Beth Onners, Anna K Ferguson, Cara Wilt, Andrew H Ko, Andrea Wang-Gillam, Daniel A Laheru, Robert A Anders, Elizabeth D Thompson, Elizabeth A Sugar, Elizabeth M Jaffee, Dung T Le
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 26 Issue 19 Pg. 5129-5139 (10 01 2020) ISSN: 1557-3265 [Electronic] United States
• PMID: 32591464 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
• Copyright: ©2020 American Association for Cancer Research.

Chemical References

• Cancer Vaccines
• Ipilimumab
• folfirinox
• Oxaliplatin
• Irinotecan
• Granulocyte-Macrophage Colony-Stimulating Factor
• Leucovorin
• Fluorouracil

Topics

• Adenocarcinoma (drug therapy, genetics, immunology, pathology)
• Aged
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects)
• Cancer Vaccines (administration & dosage, adverse effects)
• Combined Modality Therapy
• Disease-Free Survival
• Female
• Fluorouracil (administration & dosage, adverse effects)
• Gene Expression Regulation, Neoplastic (drug effects)
• Granulocyte-Macrophage Colony-Stimulating Factor (genetics)
• Humans
• Ipilimumab (administration & dosage, adverse effects)
• Irinotecan (administration & dosage, adverse effects)
• Leucovorin (administration & dosage, adverse effects)
• Macrophages (drug effects, immunology)
• Male
• Middle Aged
• Neoplasm Metastasis
• Oxaliplatin (administration & dosage, adverse effects)
• Pancreatic Neoplasms (drug therapy, genetics, immunology, pathology)
• Tumor Microenvironment (drug effects)