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Translational immune correlates of indirect antibody immunization in a randomized phase II study using scheduled combination therapy with carboplatin/paclitaxel plus oregovomab in ovarian cancer patients

A Correction to this article was published on 26 March 2020

This article has been updated

Abstract

The standard-of-care (SOC) first-line therapy for ovarian cancer (OC) patients is plagued with high relapse rates. Several studies indicated the immune system’s prominent role changing the disease course in OC patients. Chemo-immunotherapy regimens, currently being explored, include oregovomab, which is a monoclonal antibody specific for the OC associated antigen carbohydrate/cancer antigen 125 (CA125) that yielded promising results when administered together with SOC in a previous study. The QPT-ORE-002 multi-site phase II randomized study demonstrated that in patients with advanced OC, oregovomab combined with first-line SOC improved overall and progression-free survival, compared to SOC alone. The study included an Italian cohort in which we demonstrated that adding oregovomab to SOC resulted in increased patient numbers with amplified CA125-specific CD8+T lymphocytes/ml peripheral blood counts, which might explain the improved therapeutic effect of SOC + oregovomab over SOC alone. Predictive for oregovomab efficacy was a less suppressive immune environment at baseline as indicated by low numbers of circulating myeloid-derived suppressor cells, subset type 4, and a low neutrophil-and-monocyte to lymphocyte ratio.

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Change history

  • 26 March 2020

    The original version of this article unfortunately contained a mistake.

Abbreviations

ANOVA:

Analysis of variance

CA125:

Carbohydrate/cancer antigen 125

CI:

Confidence interval

DC:

Dendritic cell

ECOG:

Eastern Cooperative Oncology Group

HR:

Hazard ratio

IC:

Immune complex

iDC:

Immature dendritic cell

mDC:

Mature dendritic cell

NLR:

Neutrophil-to-lymphocyte ratio

NM:

Neutrophil-and-monocyte

NMLR:

Neutrophil-and-monocyte-to-lymphocyte ratio

OC:

Ovarian cancer

OS:

Overall survival

RFS:

Relapse-free survival

RT:

Residual tumor

SEB:

Staphylococcal enterotoxin B

SOC:

Standard of care

TILs:

Tumor-infiltrating lymphocytes

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Funding

This study was funded by OncoQuest Inc (Edmonton, AB, Canada).

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Conception and design: Alessandra Battaglia, Andrea Fattorossi, Madi R. Madiyalakan, Christopher Nicodemus and Giovanni Scambia. Development of methodology: Alessandra Battaglia, Alexia Buzzonetti, Andrea Fattorossi and Marco Fossati. Acquisition and analysis of data: Alexia Buzzonetti and Marco Fossati. Data interpretation: Alessandra Battaglia and Andrea Fattorossi. Statistical analysis: Alessandra Battaglia and Yolanda D. Mahnke with the help of ZellNet (Fort Lee, NJ, USA). Writing and reviewing of manuscript: Alessandra Battaglia, Andrea Fattorossi, Madi R. Madiyalakan, Yolanda D. Mahnke, Christopher Nicodemus and Giovanni Scambia.

Corresponding author

Correspondence to Alessandra Battaglia.

Ethics declarations

Conflict of interest

Yolanda D. Mahnke is an immunology advisor to OncoQuest. Christopher Nicodemus is a consultant to OncoQuest, Inc. and owns shares in Quest PharmaTech, Edmonton Alberta. Madi R. Madiyalakan is an employee of OncoQuest Inc. and Quest PharmaTech and owns shares in OncoQuest Inc. and Quest PharmaTech. The authors declare that there is no other conflict of interest.

Ethical approval

This QPT-ORE-002 study (clinical trial information: NCT01616303) was performed in accordance with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. It was approved by the following institutional ethics committees:

Study site numberLocationEthics committee
001Campus Biomedico University, Rome, ItalyComitato Etico dell’Università Campus Bio Medico di Roma
Via Alvaro del Portillo, 200
00128 Rome
002Fondazione Policlinico Universitario A.Gemelli IRCCS, Rome, ItalyComitato Etico dell’Università Cattolica del Sacro Cuore e Annesso Policlinico “A. Gemelli”
Largo Francesco Vito, 1
00168 Rome
003Istituto Nazionale Tumori-IRCCS, Milan, ItalyComitato Etico della Fondazione IRCCS “Istituto Nazionale dei Tumori”
Via G. Venezian, 1
20133 Milan
005Azienda Ospedaliera Cannizzaro, Catania, ItalyComitato Etico Catania 1
Via S. Sofia, 78
95123 Catania
006Azienda Ospedali Riuniti di Bergamo, Bergamo, ItalyComitato Etico della Provincia di Bergamo
Piazza OMS, 1
24127 Bergamo
007Policlinico Umberto I, Rome, ItalyComitato Etico dell’Università Sapienza
Viale del Policlinico, 155
00161 Rome

Informed consent

All patients included in the study provided written informed consent according to the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines. The informed consent, which included consent to the treatment, use of their biological specimen (peripheral blood) and data acquisition and processing, was obtained from patients prior to the initiation of the study.

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Some of the results included in this paper were previously published in a poster at the 20th biennial international meeting (November 4–7, 2017, Vienna, Austria) of the European Society of Gynaecological Oncology (ESGO).

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Battaglia, A., Buzzonetti, A., Fossati, M. et al. Translational immune correlates of indirect antibody immunization in a randomized phase II study using scheduled combination therapy with carboplatin/paclitaxel plus oregovomab in ovarian cancer patients. Cancer Immunol Immunother 69, 383–397 (2020). https://doi.org/10.1007/s00262-019-02456-z

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  • DOI: https://doi.org/10.1007/s00262-019-02456-z

Keywords

  • Oregovomab
  • Ovarian cancer
  • Immune response
  • Predictive biomarkers
  • Personalized medicine