Regional therapies are complex treatments with efficacy for extremity tumors.

CBL0137 given as a brief intra-arterial infusion was efficacious preclinically.

As a novel regional therapy agent, CBL0137 does not require circulatory isolation.

Clinical use of CBL0137 as an arterial infusion was feasible and non-toxic.

CBL0137 accumulated preferentially in tumor tissue with favorable pharmacokinetics.

Regional therapies for cancer leverage the ability to isolate the circulation to a diseased extremity or organ and deliver high doses of chemotherapy that would be systemically prohibitive due to toxicity. Virtually all regional therapies utilize the original chemotherapy agent, melphalan, which requires circulatory isolation. CBL0137 is a small molecule with multiple anti-tumor effects when given intra-arterially (IA) that shows similar efficacy to melphalan in preclinical models, but without the need for circulatory isolation.

Patients with advanced, unresectable melanoma or sarcoma (n = 5, sarcoma 60 %, melanoma 40 %) of the extremity entered a rapid dose-escalation phase of a clinical trial of IA CBL0137. CBL0137 was administered via a single IA catheter placed proximal to the site of tumor(s) in the affected extremity and delivered over 15 min. Primary objective was to define dose-limiting toxicities with secondary objectives of assessing response and pharmacokinetics (PK).

The treatments were well tolerated with minimal to no toxicity for all patients. PK data showed predictable, dose-dependent drug exposures with rapid tissue uptake and markedly decreased systemic concentrations as compared to matched intravenous dosing data. CBL0137 preferentially accumulated within tumor tissue as compared to surrounding normal tissue in the infused limb without the need for tourniquet. Sixty percent of patients treated in this protocol would not have been eligible for standard regional therapies with one patient demonstrating prolonged disease stability while avoiding major amputation.

The historic restrictions of standard regional therapies may be overcome with IA CBL0137, and this treatment is potentially applicable to a wide range of cancers beyond the extremities.

Melanoma

Sarcoma

Regional therapy

ILI

ILP

CBL0137

© 2025 The Authors. Published by Elsevier Ltd.