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Trial Testing Cancer Treatment Delivery Compound

Erkki Ruoslahti

Erkki Ruoslahti (Sanford Burnham Prebys Medical Discovery Institute)

21 August 2018. A compound designed to help cancer therapies better penetrate and kill solid tumors is being tested in its first clinical trial among patients with pancreatic cancer. The compound code-named CEND-1 by its developer DrugCendR Inc. in La Jolla, California, is based on research conducted by Sanford Burnham Prebys Medical Discovery Institute, also in La Jolla.

CEND-1 uses a pathway known as CendR that feeds nutrients into solid tumors, which are often protected by layers of fibrous tissue and a microenvironment of blood vessels and cells. This protective system helps make some solid tumor cancers, such as brain and pancreatic cancer, among the deadliest. Pancreatic cancer is often difficult to diagnose in its early stages, because of few unique symptoms associated with the disease, and because the pancreas is hidden among other organs in the body. As a result, the disease has a generally a poor prognosis for survival: 5-year survival rate of only 8 percent. American Cancer Society estimates more than 55,000 people in the U.S. will be diagnosed with pancreatic cancer this year, leading to more than 44,000 deaths.

“Cancer cells hijack processes they can use to fuel tumor growth, and the CendR pathway is one such route,” says Sanford Burnham Prebys professor Erikki Ruoslahti in an institute statement. “CEND-1 activates the CendR pathway only in tumors and not elsewhere in the body, and that allows us to sneak in a drug into the activated pathway.” Ruoslahti’s lab discovered the peptides in CEND-1, and he is the founder and CEO of DrugCendR Inc.

Preclinical studies with lab animals show peptides in CEND-1 bind to a neuropilin-1 receptor that activates the CendR pathway. CEND-1 doesn’t treat the tumor; that’s the job of the cancer drugs it escorts into the tumor. “We expect that CEND-1 will be used with the anti-cancer drugs patients already receive,” notes Ruoslahti. “CEND-1 doesn’t modify drugs, but it can streamline their deep penetration into tumors.”

The early-stage clinical trial is recruiting 34 patients at 4 sites in Australia with metastatic, or spreading, pancreatic cancer to test the safety and dosage levels of CEND-1 in combination with current chemotherapy drugs nab-paclitaxel and gemcitabine, given currently to treat pancreatic cancer. The drugs are being given as infusions once a week for 3 weeks, followed by a week with no drugs. After the first 4 weeks, the cycle of the 3 weekly infusions and 1 week without drugs will be continued in an expansion phase as long as patients are benefiting from the treatments, or the disease progresses further.

The study team is looking primarily for signs of adverse effects and to find the optimum dose. But the researchers are also looking for chemical activity of the drugs in the body, as well as signs of clinical benefit to the patients, including partial and full remission of the disease.

Ruoslahti believes CEND-1 can help patients with many more types of solid tumor cancer. “While this initial study focuses on pancreatic cancer,” he adds, “mouse experiments show that it works for many different kinds of solid tumors, including breast, brain, lung and ovarian cancers, and melanoma.”

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