A Phase I Study of Apolizumab, an Anti-HLA-DR ß-chain Monoclonal Antibody, in Patients With Solid Tumor Malignancies.

Background: Human leukocyte antigen (HLA)-DR, a member of the major histocompatibility complex class II antigen family, is a target for antibody-based therapeutics. Apolizumab (Hu1D10, Remitogen), a humanized IgG1 monoclonal anti-HLA-DR ß-chain antibody targets the antigen, 1D10, expressed on a wide variety of hematologic and solid tumor malignancies. In this Phase 1 trial, the maximum tolerated dose and dose-limiting toxicity of weekly apolizumab in patients with advanced solid tumor malignancies were determined.

First-Line Aldoxorubicin vs Doxorubicin in Metastatic or Locally Advanced Unresectable Soft-Tissue Sarcoma: A Phase 2b Randomized Clinical Trial.

Importance: Standard therapy for advanced soft-tissue sarcoma has not changed substantially in decades, and patient prognosis remains poor. Aldoxorubicin, a novel albumin-binding prodrug of doxorubicin, showed clinical activity against advanced soft-tissue sarcoma in phase 1 studies.

Objective: To evaluate efficacy and safety of aldoxorubicin vs doxorubicin in patients with advanced soft-tissue sarcoma.

Pharmacokinetic study of aldoxorubicin in patients with solid tumors.

Introduction Aldoxorubicin, a prodrug of doxorubicin, binds covalently to serum albumin in the bloodstream and accumulates in tumors. Aldoxorubicin can be administered at doses several-fold higher than doxorubicin can, without associated acute cardiotoxicity. Purpose This study fully evaluated the pharmacokinetic profile of aldoxorubicin (serum and urine).

A phase 1B/2 study of aldoxorubicin in patients with soft tissue sarcoma.

Background: Aldoxorubicin, a prodrug of doxorubicin, covalently binds to serum albumin, allowing for the administration of much higher doses of doxorubicin in a previous clinical study. The current phase 1B/2 study evaluated the safety of aldoxorubicin, including preliminary efficacy and safety of its maximum tolerated dose (MTD).

Methods: Patients aged 18 to 70 years with recurrent/refractory malignant solid tumors received aldoxorubicin at a dose of 230 mg/m(2) , 350 mg/m(2) , or 450 mg/m(2) (170 mg/m(2) , 260 mg/m(2) , or 335 mg/m(2) doxorubicin equivalents, respectively) by intravenous infusion once every 21 days for up to 8 consecutive cycles.

In vivo pharmacodynamic effects of Hu1D10 (remitogen), a humanized antibody reactive against a polymorphic determinant of HLA-DR expressed on B cells.

The humanized monoclonal antibody Hu1D10 (Remitogen, Protein Design Labs, Fremont, CA) recognizes a polymorphic determinant of human leukocyte antigen-DR expressed on the majority of B-cell lymphomas and on normal B cells of most individuals. Hu1D10 mediates complement-mediated cytotoxicity, antibody-dependent cell-mediated cytotoxicity, and apoptosis of 1D10 antigen (Ag)-positive B cells in vitro. The 1D10 Ag is expressed on a variety of tissues but is restricted primarily to lymphocytes, macrophages, and mesenchymal dendritic cells.