Joseph Skitzki, MD
Associate Professor of Surgical Oncology, Surgery, Immunology
Roswell Park Comprehensive Cancer Center, United States
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
The study drug CBL0137 is in a new class of agents termed “curaxins” that possess favorable characteristics for regional therapies (high solubility, non-genotoxic DNA stress, preferential tumor tissue accumulation). Preclinical murine isolated limb studies of CBL0137 showed superior efficacy to melphalan with reduced toxicity and serve as the basis for an on-going clinical trial of intra-arterial (IA) administration in locally advanced extremity melanoma and sarcoma patients.
Methods: Data acquired from prospective evaluation of patients treated in the Phase I rapid dose escalation of clinical trial NCT03727789.
Results:
The characteristics, toxicity, and on-going outcomes of the first 3 patients (that failed all other options) treated in the rapid dose escalation phase are reported. All patients received CBL0137 at doses specified with IA infusion over 15 minutes via catheter placed in interventional radiology with acute monitoring of clinical toxicity and Cr and CK. Patient #1 (locally advanced popliteal sarcoma, lymphedema, referred prior to AKA) received 10 mg with no acute or chronic toxicities and stable lymphedema. Disease stability before slight progression at 22 months with continued limb function. Patient #2 (locally advanced proximal thigh sarcoma) received 20 mg via IA catheter placed in proximal external iliac artery – branches noted to feed proximal tumor via epigastric (ILI or ILP not possible as femoral vein thrombosed, extensive tumor above tourniquet level). No toxicity, continued disease progression. Patient #3 (diffuse in-transit disease of lower leg) received 30 mg via IA catheter; body builder who resumed all activity within 1 week; no toxicity, clinical course on-going.
Conclusions: The first 3 patients treated in the rapid dose escalation phase demonstrate the safety of the drug at early doses. Unappreciated at the time the trial was written, patients with lymphedema, venous obstruction, disease too proximal for tourniquet, and active lifestyles showed no evidence of “functional” toxicity that can be associated with ILI or ILP. Potential responses were noted at doses expected to be below presumed therapeutic threshold.