Four-Drug Combination Tested in Metastatic Pancreatic Cancer

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Can two drugs not normally used for pancreatic cancer be combined with checkpoint inhibitors to treat metastatic disease?

Researchers keen to unleash the potential of immunotherapy for pancreatic cancer patients are bringing new drug candidates into the mix, including some that were created for different conditions entirely.

Tadalafil (Cialis), best known for its use in erectile dysfunction, is being tested alongside an experimental drug which uses Listeria bacteria to activate strong immune responses against specific tumor-associated antigens. The trial also includes the immunotherapy drugs pembrolizumab (Keytruda) and ipilimumab (Yervoy).

The phase II study will track the safety, efficacy, and immune response of the combination over the course of 18 weeks.

How Do the Drugs Work?

Pembrolizumab and ipilimumab are checkpoint inhibitors. Pembrolizumab triggers T cells to find and kill cancer cells. Ipilimumab, used to treat melanoma, halts cancer cell growth and re-engages the T cells, allowing the immune system to work more quickly—taking the “brakes” off—and attack the cancer.

Tadalafil is approved by the FDA to treat erectile dysfunction, benign prostatic hyperplasia, and pulmonary arterial hypertension. Its ability to increase blood flow to parts of the body has also made it a candidate for repurposing it as an anticancer drug. Scientists believe it may be effective in targeting myeloid-derived suppressor cells (MDSCs), which can suppress T cell responses, inducing death receptor signaling and enhancing immunotherapy and chemotherapy agents.

CRS-207 is a new drug candidate created by engineering strains of Listeria monocytogenes to express tumor-associated antigens and stimulate an immune response against mesothelin, an antigen that is overproduced by pancreatic tumors. Mesothelin, which also helps cancer cells spread, is found only in limited amounts in normal tissues.

Participating in the Trial

This trial is for patients with metastatic pancreatic cancer whose first line of treatment has not stopped the disease (second-line therapy). Researchers are looking for immune system response and effectiveness against the disease as well as toxicity of the treatment.

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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