Chemotherapy vials (National Cancer Institute, NIH)
1 April 2019. Early results from a clinical trial show a combination of immunotherapy and chemotherapy drugs shrunk tumors in most participants with pancreatic cancer. Findings from the trial, which include a high rate of adverse effects, were presented yesterday at the annual meeting of American Association for Cancer Research, or AACR, in Atlanta.
A team from the Parker Institute for Cancer Immunotherapy, a consortium of cancer researchers from academic labs, and the companies Apexigen Inc. in San Carlos, California and drug maker Bristol-Myers Squibb in Princeton, New Jersey reported the first results from a trial testing Apexigen’s experimental cancer therapy code-named APX005M in patients with pancreatic cancer. APX005M is designed to stimulate production of a receptor protein known as CD40 on the surface of white blood cells that activates both the innate and adaptive immune systems. The activated immune system then promotes specific tumor-fighting cells, normally held in check in people with solid tumor cancers.
Pancreatic cancer is often difficult to diagnose in its early stages, due to few unique symptoms associated with the disease, and because the pancreas is hidden among other organs in the body. As a result, it is often diagnosed in later, more advanced stages of the disease, with generally a poor prognosis for survival: 5-year survival rate of only 8 percent. American Cancer Society estimates nearly 57,000 people in the U.S. will be diagnosed with pancreatic cancer this year, leading to more than 45,000 deaths. Participants in the trial were diagnosed with pancreatic ductal adenocarcinoma, the most common form of this type of cancer.
Apexigen is testing APX005M as a cancer treatment on its own and, as in this case, in combination with other drugs. The early-stage trial initially planned to test the safety of APX005M working alone, but added later a test of the drug with other cancer treatments: chemotherapy drugs gemcitabine and nab-paclitaxel prescribed for pancreatic cancer, and the immunotherapy drug nivolumab, marketed as Opdivo by Bristol-Myers Squibb. Nivolumab is a synthetic antibody that limits a protein called programmed cell death-1 or PD-1 preventing activation of T-cells in the immune system, which in turn encourages progression of tumors.
In this study, 30 participants with metastatic, or spreading, pancreatic ductal adenocarcinoma received the chemotherapy drugs gemcitabine and nab-paclitaxel and APX005M. Half of the was group randomly assigned to also receive nivolumab, with all participants tracked for a median period of 32 days.
Since the trial is still underway, the paper reports on the first 24 of these participants. The results show tumor shrinkage in 20 of the 24, or 83 percent, of participants. But the results also show a high rate of adverse effects. More than half, 13 of the 24 participants or 54 percent, had to discontinue the trial due to adverse effects, with 10 participants reporting effects rated serious in nature.
Two patients experienced a fever associated with chemotherapy called febrile neutropenia, which limited their drug doses. And 4 participants died, 2 from progression of their cancer and 2 as a result of septic shock from their neutropenia. Nonetheless, the researchers say these adverse effects are expected and manageable, and several participants continued their treatments for more than a year.
Researchers from 7 Parker Institute labs took part in the trial, including University of Pennsylvania medical school. One of the UPenn researchers, Robert Vonderheide notes in a university statement, “Seeing patients continue treatment for this length of time does give us hope that this combination approach holds promise, especially when you consider that for stage 4 pancreatic cancer, the median survival is just 2 to 6 months.”
More from Science & Enterprise:
- Trial Testing Targeted Solid Tumor Immunotherapy
- Sequencing IDs Pancreatic Cancer Targets
- Gene Editing Deactivates Cause of T-Cell Side Effects
- Start-Up Raises $10.5M for Precision Immunotherapies
- Biotech, Univ. Lab Partner on Cancer Antibodies
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