dc.contributor
Institut Català de la Salut
dc.contributor
[Geva R] Sourasky Medical Center, Tel-Aviv university, Tel-Aviv, Israel. [Vieito M, Bardina J, Garralda E] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Ramon J, Corral E] START Madrid-CIOCC, Centro Integral Oncológico Clara Campal, Madrid, Spain. [Perets R] Rambam Medical Center, and Technion–Israel Institute of Technology, Haifa, Israel. [Pedregal M] START Madrid-FJD, Hospital Fundacion Jimenez Diaz, Madrid, Spain
dc.contributor
Vall d'Hebron Barcelona Hospital Campus
dc.contributor.author
Geva, Ravit
dc.contributor.author
Ramon, Jorge
dc.contributor.author
Perets, Ruth
dc.contributor.author
Pedregal, Manuel
dc.contributor.author
Corral De la Fuente, Elena
dc.contributor.author
Bardina Santos, Jorge
dc.contributor.author
Vieito , Maria
dc.contributor.author
GARRALDA, Elena
dc.date.accessioned
2025-10-25T05:39:47Z
dc.date.available
2025-10-25T05:39:47Z
dc.date.issued
2024-10-10T10:01:20Z
dc.date.issued
2024-10-10T10:01:20Z
dc.date.issued
2024-08-06
dc.identifier
Geva R, Vieito M, Ramon J, Perets R, Pedregal M, Corral E, et al. Safety and clinical activity of JNJ-78306358, a human leukocyte antigen-G (HLA-G) x CD3 bispecific antibody, for the treatment of advanced stage solid tumors. Cancer Immunol Immunother. 2024 Aug 6;73(10):205.
dc.identifier
https://hdl.handle.net/11351/12046
dc.identifier
10.1007/s00262-024-03790-7
dc.identifier
001285334500008
dc.identifier.uri
http://hdl.handle.net/11351/12046
dc.description.abstract
Dose escalation study; Human leukocyte antigen-G; Solid tumors
dc.description.abstract
Estudio de escalada de dosis; Antígeno leucocitario humano G; Tumores sólidos
dc.description.abstract
Estudi d'escalada de dosis; Antigen leucocitari humà G; Tumors sòlids
dc.description.abstract
Background
JNJ-78306358 is a bispecific antibody that redirects T cells to kill human leukocyte antigen-G (HLA-G)-expressing tumor cells. This dose escalation study evaluated the safety, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of JNJ-78306358 in patients with advanced solid tumors.
Methods
Adult patients with metastatic/unresectable solid tumors with high prevalence of HLA-G expression were enrolled. Dose escalation was initiated with once-weekly subcutaneous administration with step-up dosing to mitigate cytokine release syndrome (CRS).
Results
Overall, 39 heavily pretreated patients (colorectal cancer: n = 23, ovarian cancer: n = 10, and renal cell carcinoma: n = 6) were dosed in 7 cohorts. Most patients (94.9%) experienced ≥ 1 treatment-emergent adverse events (TEAEs); 87.2% had ≥ 1 related TEAEs. About half of the patients (48.7%) experienced CRS, which were grade 1/2. Nine patients (23.1%) received tocilizumab for CRS. No grade 3 CRS was observed. Dose-limiting toxicities (DLTs) of increased transaminases, pneumonitis and recurrent CRS requiring a dose reduction were reported in 4 patients, coinciding with CRS. No treatment-related deaths reported. No objective responses were noted, but 2 patients had stable disease > 40 weeks. JNJ-78306358 stimulated peripheral T cell activation and cytokine release. Anti-drug antibodies were observed in 45% of evaluable patients with impact on exposure. Approximately half of archival tumor samples (48%) had expression of HLA-G by immunohistochemistry.
Conclusion
JNJ-78306358 showed pharmacodynamic effects with induction of cytokines and T cell activation. JNJ-78306358 was associated with CRS-related toxicities including increased transaminases and pneumonitis which limited its dose escalation to potentially efficacious levels.
Trial registration number ClinicalTrials.gov (No. NCT04991740).
dc.description.abstract
This study was sponsored by Janssen Research & Development, LLC, USA.
dc.format
application/pdf
dc.publisher
Springer Nature
dc.relation
Cancer Immunology, Immunotherapy;73(10)
dc.relation
https://doi.org/10.1007/s00262-024-03790-7
dc.rights
Attribution 4.0 International
dc.rights
http://creativecommons.org/licenses/by/4.0/
dc.rights
info:eu-repo/semantics/openAccess
dc.subject
Càncer - Tractament
dc.subject
Immunoglobulines - Ús terapèutic
dc.subject
Immunoglobulines - Administració
dc.subject
DISEASES::Neoplasms
dc.subject
Other subheadings::Other subheadings::Other subheadings::/drug therapy
dc.subject
CHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Proteins::Blood Proteins::Immunoproteins::Immunoglobulins::Antibodies::Antibodies, Bispecific
dc.subject
Other subheadings::Other subheadings::Other subheadings::/administration & dosage
dc.subject
CHEMICALS AND DRUGS::Amino Acids, Peptides, and Proteins::Proteins::Glycoproteins::Membrane Glycoproteins::Histocompatibility Antigens Class I::HLA-G Antigens
dc.subject
ENFERMEDADES::neoplasias
dc.subject
Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia
dc.subject
COMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::proteínas::proteínas sanguíneas::inmunoproteínas::inmunoglobulinas::anticuerpos::anticuerpos biespecíficos
dc.subject
Otros calificadores::Otros calificadores::Otros calificadores::/administración & dosificación
dc.subject
COMPUESTOS QUÍMICOS Y DROGAS::aminoácidos, péptidos y proteínas::proteínas::glicoproteínas::glicoproteínas de membranas::antígenos de histocompatibilidad de clase I::antígenos HLA-G
dc.title
Safety and clinical activity of JNJ-78306358, a human leukocyte antigen-G (HLA-G) x CD3 bispecific antibody, for the treatment of advanced stage solid tumors
dc.type
info:eu-repo/semantics/article
dc.type
info:eu-repo/semantics/publishedVersion
