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

Abstract

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.

PATIENTS AND METHODS:

Eligible patients with refractory solid tumors were initially screened for ID10 Ag on their tumor. Patients whose tumors expressed 1D10 were administered apolizumab 0.5, 1.0, 1.5, or 3.0 mg/kg intravenously over 90 minutes weekly for 4 consecutive weeks, followed by a 4-week break, and assessment of response. Patients whose disease had not progressed were offered additional treatment.

RESULTS:

Tumors from 75 patients were screened for 1D10 Ag of which 17 patients were positive and underwent treatment. The first 3 dose levels were well-tolerated. Dose-limiting toxicities of grade 3 infusion-related hypersensitivity reactions and grade 3 headache and hypertension occurred in 2 patients, respectively, at apolizumab 3.0 mg/kg. Four patients, 1 each with breast carcinoma, melanoma, renal cell carcinoma, and sarcoma had stable disease for a median of 15 weeks (range: 12 to 19 wk).

CONCLUSION:

Apolizumab can be administered safely at a maximum tolerated dose of 1.5 mg/kg for 4 consecutive weeks. Adverse events and limited clinical data in both hematologic and solid tumor malignancies resulted in discontinuation of clinical development of apolizumab. HLA-DR remains an interesting immunotherapeutic target.

• Authors: Paula M Fracasso, Sherry A Goodner, Jonathan D Wildi, Michael J Naughton, Gerald P Linette, Ramaswamy Govindan, Benjamin R Tan, Kristie A Blum, Gary J Jones, Tillman E Pearce, Daniel J Levitt, Gerald H Clamon
• Journal: American journal of clinical oncology (Am J Clin Oncol) Vol. 45 Issue 7 Pg. 294-297 (07 01 2022) ISSN: 1537-453X [Electronic] United States
• PMID: 35700081 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• HLA-DR Antigens
• apolizumab

Topics

• Antibodies, Monoclonal (adverse effects)
• Antibodies, Monoclonal, Humanized
• Carcinoma, Renal Cell (drug therapy)
• HLA-DR Antigens (therapeutic use)
• Humans
• Kidney Neoplasms (drug therapy)
• Maximum Tolerated Dose
• Neoplasms (chemically induced, drug therapy)