Guest Column | June 19, 2024

Trans-Arterial Micro-Perfusion For Improved Drug Delivery

By Shaun Bagai, CEO, RenovoRx Inc.

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The majority of benign and malignant tumors thrive in a highly vascularized microenvironment. Tumors depend on existing or newly formed blood supply to receive oxygen and nutrients, making tumor vasculature an important conduit or “highway” for anticancer therapeutics. Thus, chemotherapies and other treatments can be administered systemically through the veins (intravenous or IV delivery) in order to reach the tumor site. However, hypovascular tumors have a paucity of blood vessels that feed into certain solid tumors. This characteristic of these tumors presents a challenge to deliver drugs systemically as adequate dose levels of effective therapeutics are limited from getting to target cells and most current chemotherapies have an already narrow therapeutic index (the delta between the efficacious dose and a toxic dose).

Trans-arterial micro-perfusion (TAMP) is a novel approach designed to use pressure to deliver therapeutic agents directly to tumor sites, enabling precision medicine at a locoregional level. Unlike systemic drug delivery methods, TAMP targets specific tumor regions, to minimize systemic toxicities and increase concentration of a therapy delivered at the tumor site.

In oncology, systemic drug delivery methods often fall short to deliver to the target site, especially in difficult-to-access tumors such as pancreatic, biliary, brain, lung, or bladder cancer. The emergence of TAMP has enabled a new era of precision medicine, with significant advantages in the management of challenging malignancies.

Significant Advantages With Localized Delivery

Through locoregional, pressurized drug delivery, TAMP observed a 100-fold improvement in concentrations of chemotherapy compared to IV administration in pre-clinical studies. Additionally, clinically, TAMP has shown the ability to reduce systemic exposure of the drug by over 50% while administering the full IV dose locoregionally instead of IV delivery in a pharmacokinetic (PK) sub-study within a currently ongoing Phase 3 study for the treatment of locally advanced pancreatic cancer (LAPC). The delivery device used to perform TAMP is cleared by the FDA to deliver therapeutic agents, including chemotherapy, to the peripheral vascular system.

Specifically, pancreatic cancer represents a challenging malignancy where traditional drug delivery methods have shown limited efficacy. The dense desmoplastic stroma and poor vascularization of pancreatic tumors hinder drug penetration, rendering systemic chemotherapy less effective. However, TAMP offers a promising solution by delivering therapeutic agents directly to bathe pancreatic tumors.

Promise For Treating Solid Tumors Including Pancreatic Cancer, Bile Duct Cancer, Lung Cancer, Uterine Tumors And Glioblastoma

In completed RR1 Phase 1/2 and RR2 observational registry studies, TAMP demonstrated a median overall survival (“OS”) of 27.9 months in LAPC patients pre-treated with radiation followed by treatment with TAMP. The expected survival of LAPC patients is roughly 12 to 18 months in patients receiving only IV systemic chemotherapy or IV chemotherapy plus radiation. The RR3 Phase 3 TIGeR-PaC clinical trial was launched after the conclusion of the RR1 Phase 1/2 study.

The Phase 3 study is investigating the efficacy and safety of a drug-device combination (intra-arterial gemcitabine + catheter) utilizing TAMP in LAPC versus the current standard of care, systemic IV chemotherapy, and has shown promising interim results.

The combination of the first interim analysis data and subsequent data monitoring committee (DMC) recommendation for the trial to continue provides early signals of TAMP’s potential transformation of the treatment landscape for pancreatic cancer, offering new hope for patients with this aggressive disease.

Beyond the delivery of chemotherapies, like gemcitabine, TAMP is also being explored with immunotherapeutics. Additional agents with systemic toxicities such as radiopharmaceuticals, antibody–drug conjugates (ADCs), checkpoint inhibitors, and other modalities are potentially synergistic with this novel approach. Trans-arterial therapies have emerged as crucial interventions for additional clinical indications like bile duct cancer, lung cancer, uterine tumors and glioblastoma. In addition to its efficacy in treating specific tumor types, TAMP offers a range of benefits over traditional drug delivery methods. By delivering therapeutic agents directly to tumor sites, TAMP minimizes systemic exposure and off-target toxicity, thereby improving patient tolerance and quality of life. Furthermore, TAMP may allow for the use of higher drug concentrations, potentially enhancing therapeutic efficacy without compromising safety.

Keeping An Eye On TAMP As A Paradigm Shift As Research Continues

TAMP represents a potential paradigm shift in the treatment of cancer, by offering a targeted and personalized approach to treatment. By harnessing the principles of targeted drug delivery and exploiting the lack of tumor vasculature, TAMP has the potential to revolutionize cancer care and improve outcomes for patients with challenging malignancies.

Through targeted and localized drug delivery, TAMP offers potential significant advantages in the treatment of difficult-to-treat tumors, including improved efficacy, reduced toxicity, and enhanced patient outcomes. As ongoing research continues to unravel the full potential of TAMP, it is quickly emerging as a novel therapeutic approach, in a new era of precision medicine.