Phase 1 carfilzomib selective proteasome inhibitor via hepatic artery infusion pump for liver metastases

This National Cancer Institute (NCI) Phase 1, open-label, single-arm study tests whether carfilzomib—a selective proteasome inhibitor (approved as Kyprolis by Amgen)—can be safely delivered continuously through an existing hepatic artery infusion (HAI) pump directly into the liver. The core goal is dose-finding and safety, with dose-limiting toxicities assessed in Cycle 1 (28 days) and treatment continuing up to about 6 months in eligible participants. It enrolls adults with liver-dominant, unresectable metastases from colorectal cancer, adrenocortical carcinoma, or cholangiocarcinoma whose disease persists after prior HAI pump therapy and who still have a functioning pump. The scientific/commercial angle is repurposing a hematology proteasome inhibitor as a regional liver-directed therapy, potentially boosting intrahepatic exposure while limiting systemic levels. For these populations after prior HAI therapy, care commonly becomes additional systemic therapy (fluoropyrimidine/oxaliplatin/irinotecan-based regimens ± biologics for colorectal cancer; gemcitabine/cisplatin-based regimens for cholangiocarcinoma; mitotane-based regimens ± chemo for adrenocortical carcinoma), plus liver-directed options when feasible—this study explores whether a new HAI payload can extend benefit after pump relapse.