Immune-Stimulating Drug with Chemotherapy Reduces Pancreatic Tumor Size

A recent small phase 1b clinical trial found that an experimental immune-stimulating drug is able to control the growth of pancreatic tumors, opening the door for patients to be eligible for surgery.

“Since surgery currently provides the best chance for survival of pancreatic cancer, any research that helps to move more patients toward that goal is exciting,” said David C. Linehan, lead author of a study published in The Lancet Oncology.

Patients with advanced pancreatic cancer that cannot be surgically removed have a median 5 year survival rate of less than 5%.

The study enrolled 47 patients with locally advanced pancreatic ductal adenocarcinoma to test Pfizer’s new drug PF-04136309.

A majority of participants were administered PF-04136309, in addition to a standard 4-drug chemotherapy regimen, while the rest of the patients received chemotherapy alone.

The results of the study showed that a large portion of patients who received PF-04136309 had their tumors stop growing, while others saw their tumors shrink by more than 30%. One patient even had their tumors disappear completely.

Most of the drug’s side effects were found to be no worse than standard chemotherapy, but 3 patients did withdraw from the study because of toxicity.

In addition to the study’s results, researchers discovered that PF-04136309 inhibits CCR2 (the precursors of tumor-assisted macrophages - TAMs) and reduced the number of cells critical for creating the harmful microenvironment. When used in combination with chemotherapy, the drug seemed to galvanize a proper immune response in participants.

In pancreatic cancer patients, approximately 80% of tumors are comprised of TAMs (non-cancer cells), which play a key role in aiding cancer growth and blocking the immune system from attacking cancer cells.

Prior research conducted by Linehan involved the investigation of TAMs in the dense tissues, as well as the microenvironment surrounding pancreatic tumors.

During that research, it was found that pancreatic cancer patients with high levels of TAMs were more likely to have a recurrence of cancer after surgery. Several mouse studies revealed that PF-04136309 blocked the mobilization of these cells, which was confirmed in the phase 1b clinical trial.

Initially, researchers predicted that the results of the current study would reveal that only 25% of patients in the study would respond to PF-04136309. However, the response rate was nearly double the rate of individuals treated with chemotherapy alone.

The trial results concluded that the targeted experimental drug were deemed safe and tolerable.

Linehan has partnered with Pfizer to lead a larger, randomized phase 2 clinical trial to test PF-04136309 on patients with metastatic cancer who have a prognosis of 6 to 12 months.