Immunotherapy shows promise as treatment for pancreatic cancer
CAN-2409 shows trends toward improved survival in Phase 2 trial patients
Treatment with CAN-2409, an immune-modulating anticancer therapy, showed promising trends toward improved survival in a Phase 2 clinical trial involving people with pancreatic cancer, according to new data announced by its developer Candel Therapeutics.
In fact, “final survival data … showed notable improvement in estimated median overall survival of 31.4 months after experimental treatment with CAN-2409 versus only 12.5 months in the control group,” the company said in a press release.
Spurred by the findings, Candel is now planning to launch another larger study to test CAN-2409 as a treatment for pancreatic cancer.
“The notable benefits observed with CAN-2409 in this clinical trial, including evidence of a long tail of survival, highlights the transformative potential of this biological multimodal immunotherapy in difficult to treat cancers,” said Paul Peter Tak, MD, PhD, CEO and president of Candel, noting the treatment’s potential for “improving long-term survival.”
Tak noted that, “based on these promising findings, the company has decided to prepare for a larger, late-stage randomized controlled clinical trial of CAN-2409 in [pancreatic cancer].”
Trial testing pancreatic cancer treatment candidate enrolled 13 patients
Treatment with CAN-2409 involves injecting a patient’s tumor with a virus that carries a gene providing instructions to make an enzyme called herpes simplex virus thymidine kinase (HSV-tk). Patients are then given an oral antiviral therapy called valacyclovir. The HSV-tk enzyme converts valacyclovir into a toxic molecule that kills cancer cells.
Importantly, according to the company, the therapy is designed to kill cancer cells in a way that alerts the immune system that something is wrong. That is expected to prime the immune system to go on the attack against any remaining cancer cells in much the same way that a vaccine would.
W. Garrett Nichols, MD, Candel’s chief medical officer, noted that “CAN-2409 is a first-in-class multimodal immunotherapy candidate” for pancreatic cancer.
The treatment, “designed for … vaccination against the patient’s tumor, … offers the potential to control this disease and to prolong survival, thus improving outcomes following [the] dismal prognosis” that typically follows a pancreatic cancer diagnosis, Nichols said.
The Phase 2 study (NCT02446093) testing CAN-2409 enrolled 13 people with pancreatic ductal adenocarcinoma, known as PDAC, which is the most common form of pancreatic cancer. To be eligible for the trial, participants had to have tumors that were borderline resectable, meaning removable by surgery, and that had not metastasized or spread to other parts of the body.
All participants received standard-of-care pancreatic cancer treatment like chemotherapy and/or radiation. Seven patients also were given treatment with CAN-2409, while the other six, serving as controls, did not.
“Patients with borderline resectable PDAC often have undetectable metastases that are not cleared with current standard of care … chemoradiation and surgery,” Nichols noted.
Earlier data showed that, after two years, the survival rate was higher in patients given CAN-2409 compared with those given only standard-of-care therapy (71.4% vs. 16.7%).
Now, new data show that the estimated median survival time for patients given CAN-2409 was slightly longer than 31 months, or more than 2.5 years. By contrast, in patients who didn’t receive CAN-2409, the estimated median survival time was approximately one year.
The median survival after disease progression was also longer with CAN-2409 than with standard of care alone (21.2 vs. 7.2 months).
3 of the 7 patients given CAN-2409 in Phase 2 trial are still alive
As of late February, according to Candel, three of the patients given CAN-2409 are still alive.
Since enrollment in the trial, two of these individuals have been alive for more than five years, while the third has survived nearly three years since entering the study. These long survival times were seen even though some of the patients had undetected metastases or residual tumor at the resection margin after surgery. Such factors usually are associated with worse outcomes for cancer patients.
By contrast, one patient not given CAN-2409 is still alive more than five years after enrolling in the study, the company reported. According to Candel, this patient’s tumor showed features that are associated with better outcomes irrespective of treatment.
Data from the trial have also suggested that CAN-2409 seems to be working as intended.
The data … support the potential of CAN-2409 across various solid tumors, by showing its potential to alter the balance between the pancreatic tumor and the antitumor immune response. … [Treatment improved] long-term survival in a subset of the patients.
Analyses of tumor samples showed that patients given CAN-2409 had increased levels of cancer-killing immune cells, which were not seen in individuals who received only standard-of-care treatment. Those given CAN-2409 also showed increased levels of inflammatory signaling molecules in their blood that were not seen in patients given standard-of-care only.
According to Tak, “the data … support the potential of CAN-2409 across various solid tumors, by showing its potential to alter the balance between the pancreatic tumor and the antitumor immune response, even in patients with residual tumor.”
Tak noted that treatment was found to “[improve] long-term survival in a subset of the patients.”
CAN-2409 was generally well tolerated, according to Candel, with no dose-limiting toxicities, or side effects suggesting that the dose of therapy is too high to be used safely.
About the Author
