Emerging antibody therapies for pancreatic adenocarcinoma: a review of recent phase 2 trials

ABSTRACT

Introduction: Pancreatic adenocarcinoma is now the third-leading cause of cancer-related deaths in the US which can be attributed to rising incidence, diagnosis at advanced stages and early development of metastasis. Systemic therapy remains palliative with early development of resistance possibly related to the constitutive activation of ‘undruggable’ KRAS, immunosuppressive microenvironment, and intense desmoplasia. The advancements in molecular biology has led to the development and investigation of targeted and immune therapeutics.

Areas covered: This study provides a comprehensive review of the literature to further the understanding of molecular targets with their respective antibody-based therapies in clinical development in pancreatic cancer. PubMed was systematically searched for English-language articles discussing antibody-based therapies under phase 2 clinical trial investigation in pancreatic adenocarcinoma.

Expert opinion: PDAC remains highly resistant to chemotherapy with no significant improvement in survival for patients with advanced or metastatic cancer. Unfortunately, the majority of the antibody-based targeted and immune therapeutics have failed to meet their primary efficacy endpoints in early phase trials. However, there are a few promising antibody-based drugs with intriguing preliminary data that merit further investigation, while many more continue to be developed and investigated preclinically, and in early phase trials.

KEYWORDS:

• Pancreatic cancer
• phase 2 trials
• monoclonal antibodies
• immune microenvironment

Declaration of interest

Thomas Enzler reported institutional funding from Abbie and Exelixis Pharmaceuticals. Vaibhav Sahai reported institutional research grant funding from Agios, Bristol-Myers Squibb, Celgene, Clovis, Fibrogen, Incyte, Ipsen, Medimmune, Merck, NCI and Rafael Pharmaceuticals. Vaibhav Sahai is also a consultant for Astrazeneca, QED, Incyte, GSK, and Rafael Pharmaceuticals. 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 apart from those disclosed.

Reviewer disclosures

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

Additional information

Funding

This paper was not funded.