A New Immunotherapy Combination for Metastatic Pancreatic Cancer

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Could a novel combination of monoclonal antibodies block abnormal cell growth and restore antitumor activity?

Monoclonal antibodies (mAbs) are becoming increasingly popular as potential treatments for advanced cancer, as they can interfere with the ability of tumor cells to grow and spread.

A new combination of two mAbs targeting specific proteins is being studied in metastatic pancreatic cancer to determine the best dose and any toxic side effects.

Two Targets

A monoclonal antibody is a type of protein that has been designed to recognize and attach to a specific structure (called an antigen) in the body.

The first drug involved in the trial, siltuximab (Sylvant), has been designed to bind to a protein in the body called interleukin 6 (IL-6). Too much IL-6 is thought to contribute to the abnormal cellular growth of tumor cells. By attaching to IL-6, siltuximab blocks its activity and stops abnormal cell growth. It is currently used in the treatment of certain cancers and of multicentric Castleman’s disease, a rare blood disorder caused by dysregulated IL-6 production.

The second drug in the trial, spartalizumab, is a monoclonal antibody that binds to the PD-1 protein, which negatively regulates T-cell activation. By blocking the binding between PD-1 and its interacting proteins, PD-L1 and PD-L2, spartalizumab acts like a checkpoint inhibitor, and can restore effector T cell functions and induce the immune response of T cell-mediated against tumor cells. It has been previously tested as an investigational drug for the treatment of melanoma.

Participating in This Trial

The phase Ib/II trial is open to pancreatic cancer patients with metastatic disease who have been previously treated with chemotherapy. Patients who have had prior treatment with checkpoint inhibitors are not eligible to participate.

Participants are assigned to one of three study arms (phase Ib of the study), which test different doses of siltuximab while spartalizumab is given at a consistent dose. The drugs are administered intravenously. The fourth arm (phase II of the study) tests the drug combination with the doses determined during the phase Ib For each study arm the drug cycle is repeated every three weeks in the absence of disease progression or unacceptable toxicity.

The main aim of the dose escalation trial is to determine the recommended phase II dose for the combination of the two drugs, as well as define the toxicity profile of the drug combination and evaluate its efficacy.

We encourage you to consult your physicians for clinical trials that may be right for you. The website ClinicalTrials.gov provides more details about this trial as well as many others. You can visit the EmergingMed Trial Finder for a list of all active pancreatic cancer clinical trials.

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