PMID- 35700081
OWN - NLM
STAT- MEDLINE
DCOM- 20220623
LR  - 20230903
IS  - 1537-453X (Electronic)
IS  - 0277-3732 (Print)
IS  - 0277-3732 (Linking)
VI  - 45
IP  - 7
DP  - 2022 Jul 1
TI  - A Phase I Study of Apolizumab, an Anti-HLA-DR ss-chain Monoclonal Antibody, in 
      Patients With Solid Tumor Malignancies.
PG  - 294-297
LID - 10.1097/COC.0000000000000924 [doi]
AB  - 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.
CI  - Copyright (c) 2022 Wolters Kluwer Health, Inc. All rights reserved.
FAU - Fracasso, Paula M
AU  - Fracasso PM
AD  - Department of Medicine, Washington University School of Medicine and the Alvin J. 
      Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School 
      of Medicine, St. Louis, MO.
FAU - Goodner, Sherry A
AU  - Goodner SA
AD  - Department of Medicine, Washington University School of Medicine and the Alvin J. 
      Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School 
      of Medicine, St. Louis, MO.
FAU - Wildi, Jonathan D
AU  - Wildi JD
AD  - Department of Medicine, Washington University School of Medicine and the Alvin J. 
      Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School 
      of Medicine, St. Louis, MO.
FAU - Naughton, Michael J
AU  - Naughton MJ
AD  - Department of Medicine, Washington University School of Medicine and the Alvin J. 
      Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School 
      of Medicine, St. Louis, MO.
FAU - Linette, Gerald P
AU  - Linette GP
AD  - Department of Medicine, Washington University School of Medicine and the Alvin J. 
      Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School 
      of Medicine, St. Louis, MO.
FAU - Govindan, Ramaswamy
AU  - Govindan R
AD  - Department of Medicine, Washington University School of Medicine and the Alvin J. 
      Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School 
      of Medicine, St. Louis, MO.
FAU - Tan, Benjamin R
AU  - Tan BR
AD  - Department of Medicine, Washington University School of Medicine and the Alvin J. 
      Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School 
      of Medicine, St. Louis, MO.
FAU - Blum, Kristie A
AU  - Blum KA
AD  - Department of Medicine, Washington University School of Medicine and the Alvin J. 
      Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School 
      of Medicine, St. Louis, MO.
FAU - Jones, Gary J
AU  - Jones GJ
AD  - PDL BioPharma Inc., Freemont, CA.
FAU - Pearce, Tillman E
AU  - Pearce TE
AD  - PDL BioPharma Inc., Freemont, CA.
FAU - Levitt, Daniel J
AU  - Levitt DJ
AD  - PDL BioPharma Inc., Freemont, CA.
FAU - Clamon, Gerald H
AU  - Clamon GH
AD  - Department of Internal Medicine, University of Iowa Hospital and Clinics, Iowa 
      City, IA.
LA  - eng
GR  - P30 CA086862/CA/NCI NIH HHS/United States
GR  - P30 CA091842/CA/NCI NIH HHS/United States
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20220601
PL  - United States
TA  - Am J Clin Oncol
JT  - American journal of clinical oncology
JID - 8207754
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (HLA-DR Antigens)
RN  - G88KCP51RE (apolizumab)
SB  - IM
MH  - Antibodies, Monoclonal/adverse effects
MH  - Antibodies, Monoclonal, Humanized
MH  - *Carcinoma, Renal Cell/drug therapy
MH  - HLA-DR Antigens/therapeutic use
MH  - Humans
MH  - *Kidney Neoplasms/drug therapy
MH  - Maximum Tolerated Dose
MH  - *Neoplasms/chemically induced/drug therapy
PMC - PMC9219582
MID - NIHMS1810221
COIS- The authors declare no conflicts of interest.
EDAT- 2022/06/15 06:00
MHDA- 2022/06/24 06:00
PMCR- 2023/07/01
CRDT- 2022/06/14 12:23
PHST- 2022/06/15 06:00 [pubmed]
PHST- 2022/06/24 06:00 [medline]
PHST- 2022/06/14 12:23 [entrez]
PHST- 2023/07/01 00:00 [pmc-release]
AID - 00000421-202207000-00003 [pii]
AID - 10.1097/COC.0000000000000924 [doi]
PST - ppublish
SO  - Am J Clin Oncol. 2022 Jul 1;45(7):294-297. doi: 10.1097/COC.0000000000000924. 
      Epub 2022 Jun 1.