Oregovomab: an investigational agent for the treatment of advanced ovarian cancer

ABSTRACT

Introduction: Ovarian cancer (OC) represents the leading cause of death among gynecological cancers. Despite novel compound classes like vascular endothelial growth factor (VEGF) inhibitors or poly-ADP ribose polymerase (PARP) inhibitors are available, which improve significantly efficacy of platinum-based chemotherapy, OC prognosis remains poor and innovative strategies are needed. The induction of tumor specific immune response with a therapeutic intent is a very challenging approach. Oregovomab is a murine monoclonal antibody direct to the tumor-associated antigen CA125 that stimulate a host cytotoxic immune response against tumor cells expressing CA125.

Areas covered: This paper reviews the preclinical and clinical published data underlying the use of oregovomab in advanced OC. A literature search was performed in PubMed for oregovomab, ovarian cancer, anti-CA125, and on ClinicalTrials.gov for currently ongoing trials.

Expert opinion: Oregovomab demonstrated a significant improvement in progression-free and overall survival in advanced OC treatment when administered simultaneously with first-line chemotherapy. This promising schedule is currently investigated in a phase III trial. Since oral treatments as PARP-inhibitors have recently been approved in the OC first-line setting, the possible role of oregovomab needs still to be defined, also considering the intravenous route of administration. The easy to manage toxicity profile makes oregovomab an ideal candidate for association strategies.

KEYWORDS:

• Antibody anti-CA125
• indirect immunization
• maintenance therapy
• oregovomab
• ovarian cancer

Article highlights

• Ca125 is the most widely used tumor marker in ovarian cancer. It is a high molecular weight glycoprotein raised in approximately 90% of patients with advanced epithelial ovarian cancer.

• Oregovomab is a murine monoclonal antibody with high affinity for CA125, which stimulates a host cytotoxic immune response against tumor cells expressing CA125.It is investigated as treatment option for advanced OC patients both in maintenance first-line therapy and in recurrent disease.

• Administered intravenously after complete clinical response to primary chemotherapy, oregovomab, demonstrated prolonged time to recurrence compared to placebo (24.0 versus 10.8 months) in a subanalysis of a phase II study in patients with favorable prognostic features.

• The phase III study did not confirm the efficacy previously reported.

• Oregovomab’s simultaneous administration with chemotherapy in first-line OC treatment demonstrates impressive data in terms of PFS (41.8 months for the oregovomab arm versus 12.2 months for the placebo arm) and OS (not yet been reached for oregovomab and 43.2 months for placebo) supporting the investigation of this schedule in a phase III trial, which is currently ongoing.

• Oregovomab is well tolerated with a manageable toxicity profile comparable to placebo.

• Considering the efficacy of recently approved drugs (PARP-inhibitors), the possible role that oregovomab may play in the treatment of OC, is still to be defined.

• Intravenous route of administration could be an issue for patient acceptance to treatment.

This box summarizes key points contained in the article.

Acknowledgments

We would like to thank Franziska M. Lohmeyer, PhD, Fondazione Policlinico Universitario A. Gemelli, for her support revising our manuscript.

Box 1. Drug summary box

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Declarations of interest

- A. Pietragalla worked at AstraZeneca Medical Affair Division from March 2015 to December 2018.

- S. Duranti: worked at AbbVie Medical Affair Division from July 2017 to March 2020.

- G. Daniele has served on advisory board of Beigene and received support for travel and accommodation from Roche.

- D. Lorusso has served on advisory boards for Clovis Oncology, AstraZeneca, Genmab/Seattle Genetics, MSD, ImmunoGen, PharmaMar, Roche, and Tesaro/GSK, received support for travel or accommodation from AstraZeneca, GSK and Roche and institutional research funding from Merck, GSK, Clovis, Pharmamar.

- A. Fagotti received Grant/Research Support from MSD Italia S.r.l. and personal fees from Glaxo Smith Kline p.l.c. (Tesaro), PharmaMar S.A. and Johnson & Johnson SpA.

- G Scambia has served on advisory boards for TESARO Bio Italy S.r.l, Johnson & Johnson, Clovis Oncology Italy S.r.l. He received support for travel or accommodation from MSD Italy S.r.l and Clovis Oncology Italy S.r.l, and institutional research funding from MSD Italy S.r.l.

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Declaration of interest

No potential conflict of interest was reported by the authors.