Obinutuzumab Pretreatment as a Novel Approach to Mitigate Formation of Anti-Drug Antibodies Against Cergutuzumab Amunaleukin in Patients with Solid Tumors.

Details

Serval ID
serval:BIB_CC842A12DADF
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Obinutuzumab Pretreatment as a Novel Approach to Mitigate Formation of Anti-Drug Antibodies Against Cergutuzumab Amunaleukin in Patients with Solid Tumors.
Journal
Clinical cancer research
Author(s)
Peters S., Angevin E., Alonso-Gordoa T., Rohrberg K., Melero I., Mellado B., Perez-Gracia J.L., Tabernero J., Adessi C., Boetsch C., Watson C., Dal Porto J., Dejardin D., Del Nagro C., Nicolini V., Evers S., Klein C., Leutgeb B., Pisa P., Rossmann E., Saro J., Umana P., Charo J., Teichgräber V., Steeghs N.
ISSN
1557-3265 (Electronic)
ISSN-L
1078-0432
Publication state
Published
Issued date
15/04/2024
Peer-reviewed
Oui
Volume
30
Number
8
Pages
1630-1641
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
The immunocytokine cergutuzumab amunaleukin (CEA-IL2v) showed manageable safety and favorable pharmacodynamics in phase I/Ib trials in patients with advanced/metastatic carcinoembryonic antigen-positive (CEA+) solid tumors, but this was accompanied by a high incidence of anti-drug antibodies (ADA). We examined B-cell depletion with obinutuzumab as a potential mitigation strategy.
Preclinical data comparing B-cell depletion with rituximab versus obinutuzumab are summarized. Substudies of phase I/Ib trials investigated the effect of obinutuzumab pretreatment on ADA development, safety, pharmacodynamics, and antitumor activity of CEA-IL2v ± atezolizumab in patients with advanced/metastatic or unresectable CEA+ solid tumors who had progressed on standard of care.
Preclinical data showed superior B-cell depletion with obinutuzumab versus rituximab. In clinical studies, patients received CEA-IL2v monotherapy with (n = 16) or without (n = 6) obinutuzumab pretreatment (monotherapy study), or CEA-IL2v + atezolizumab + obinutuzumab pretreatment (n = 5; combination study). In the monotherapy study, after four cycles (every 2 weeks treatment), 0/15 evaluable patients administered obinutuzumab pretreatment had ADAs versus 4/6 patients without obinutuzumab. Obinutuzumab pretreatment with CEA-IL2v monotherapy showed no new safety signals and pharmacodynamic data suggested minimal impact on T cells and natural killer cells. Conversely, increased liver toxicity was observed in the combination study (CEA-IL2v + atezolizumab + obinutuzumab pretreatment).
These preliminary findings suggest that obinutuzumab pretreatment before CEA-IL2v administration in patients with CEA+ solid tumors may be a feasible and potent ADA mitigation strategy, with an acceptable safety profile, supporting broader investigation of obinutuzumab pretreatment for ADA mitigation in other settings.
Keywords
Humans, Rituximab, Carcinoembryonic Antigen, Neoplasms/drug therapy, Antibodies, Monoclonal, Humanized
Pubmed
Web of science
Create date
09/02/2024 14:07
Last modification date
25/05/2024 7:12
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