The purpose of this study is to determine the recommended phase 2 dose (RP2D) regimen(s) of JNJ-78306358 in Part 1 (Dose Escalation) and to determine the safety of JNJ-78306358 at the RP2D regimen(s) in Part 2 (Dose Expansion).

Start Date24 Oct 2021

Sponsor / Collaborator

Janssen Research & Development LLC

100 Clinical Results associated with JNJ-78306358

100 Translational Medicine associated with JNJ-78306358

100 Patents (Medical) associated with JNJ-78306358

Literatures (Medical) associated with JNJ-78306358

Cancer Immunology, Immunotherapy

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

Article

Author: Moreno, Victor ; Ramon, Jorge ; Steinbach, Douglas ; Geva, Ravit ; Perets, Ruth ; Patel, Jaymala ; Patel, Bharvin ; Chaudhary, Ruchi ; Vieito, Maria ; Doger, Bernard ; Lauring, Josh ; Garralda, Elena ; Calvo, Emiliano ; Cao, Yu ; Wu, Shujian ; Pedregal, Manuel ; Corral, Elena ; Brown, Regina J ; Yao, Tsun-Wen Sheena ; Greger, James G ; Bardina, Jorge

AbstractBackgroundJNJ-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.MethodsAdult 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).ResultsOverall, 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.ConclusionJNJ-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).

100 Deals associated with JNJ-78306358

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Advanced Malignant Solid Neoplasm	Phase 1	IL	Janssen Research & Development LLC	24 Oct 2021
Advanced Malignant Solid Neoplasm	Phase 1	ES	Janssen Research & Development LLC	24 Oct 2021

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04991740 (Pubmed \| Cancer Immunol Immunother) Manual	Phase 1	Ovarian Cancer \| Advanced Malignant Solid Neoplasm \| Renal Cell Carcinoma \| Colorectal Cancer human leukocyte antigen-G (HLA-G)	39	JNJ-78306358	(fqeyoyiypf) = wlgpwzqfwd pqcksdkkks (qyjzdkmdxl ) View more	Positive	06 Aug 2024

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