Anti-CEA CAR-T Demonstrates Significant Therapeutic Effect in Pancreatic Cancer Patients With Liver Metastases
A concentrated dose of anti-CEA CAR-T cells administered precisely at the site of a solid tumor by Pressure-enabled Drug Delivery (PEDD) (TriSalus Life Sciences’) is safe, with encouraging clinical responses, according to the results of a phase 1b clinical trial presented in a poster at the Society for Immunotherapy of Cancer (SITC) Annual Meeting, being held November 7-11 in Washington, DC.
In the preliminary Hepatic Immunotherapy for Metastases (HITM-SURE) clinical trial, 5 patients (4 pancreatic and 1 colorectal) with carcinoembryonic antigen–positive (CEA+), unresectable stage IV adenocarcinoma with liver metastases who had failed ≥1 lines of chemotherapy were administered 3 hepatic artery infusions of autologous anti-CEA CAR-T cells (Sorrento Therapeutics) with PEDD technology, which overpowers the high pressure within solid tumors that limits the reach and efficacy of therapeutic agents.
No viable liver metastases by PET scan was found in 2 out of the 4 patients with pancreatic cancer. At 12 months follow-up, PET imaging showed no evidence of liver metastases in one patient with stage IV pancreatic carcinoma. This patient’s primary pancreatic tumor was stable. A second patient with stage IV pancreatic cancer also had no evidence of liver metastases six weeks after CAR-T/PEDD infusions.
For the 4 patients with stage IV pancreatic cancer the median overall survival postreament was 8.3 months. One patient died of causes unrelated to the study. No patient suffered a severe adverse event related to the CAR-T or device.
“PEDD significantly increased CAR-T within liver metastases when compared with low-pressure microcatheters, and this was associated with encouraging clinical activity in two subjects,” said Steven Katz, MD, director of the Office of Therapeutic Development at the Roger Williams Medical Center, and the principal investigator of the trial, in a press release. “These early results suggest we may be able to achieve a therapeutic dose in solid tumors and avoid severe side effects, such as neurotoxicity and cytokine release syndrome, that are prevalent with conventional systemic CAR-T administration methods.”
“Although this is an early study, we are hopeful CAR-T immunotherapy in combination with our PEDD technology can help prolong the lives of patients with pancreatic and other high-pressure solid tumors,” said Mary T. Szela, CEO and president of TriSalus Life Sciences. “Localized infusion with the company’s technology has been used in nearly 8,000 procedures worldwide for liver cancer, with proven ability to improve tumor uptake.”
TriSalus™ Life Sciences. TriSalus Life Sciences’ Pressure-Enabled Drug Delivery (PEDD) Significantly Increased Therapeutic Effect of Anti-CEA CAR-T in Pancreatic Cancer Patients with Liver Metastases [press release]. 2018. http://trisaluslifesci.com/docs/SITC-release.pdf.