P1, N=32, Suspended, Groupe Oncologie Radiotherapie Tete et Cou | Recruiting --> Suspended

P1, N=200, Recruiting, Oxford BioTherapeutics Ltd | N=150 --> 200 | Trial completion date: Dec 2024 --> Dec 2027 | Trial primary completion date: Dec 2023 --> Dec 2026

P1, N=32, Not yet recruiting, Groupe Oncologie Radiotherapie Tete et Cou

Here we report on a potential novel immuno-oncology mechanism revealed during the Translational Phase I (NCT04064359) immuno-blood profiling of a chemo-refractory patient treated with OBT076, an experimental CD205-directed ADC.A chemo-refractory advanced gastric cancer patient with 60% CD205 expression in the primary tumor via IHC and having previously undergone 2 lines of chemotherapy treatment (Docetaxel/cisplatin/5FU and Ramucirumab/Paclitaxel), received five 21-day cycles of OBT076 (one at 2.5mg/kg and four cycles at 2.0 mg/kg) followed by 1 cycle of Pembrolizumab (PZ; 200mg) ~4 weeks later...These findings suggest that OBT076 activates the patient’s immune response against the tumor through a potentially novel mechanism: drug-induced depletion of CD8+ CD205+ immuno-suppressive cells and subsequent T-cell activation. Additionally, our data support the use of immune checkpoint inhibitors in conjunction with OBT076 to achieve favorable clinical outcomes.

Small‑molecule γ‑secretase inhibitors (AL101, MRK‑560, nirogacestat and others) and antibody‑based biologics targeting Notch ligands or receptors [ABT‑165, AMG 119, rovalpituzumab tesirine (Rova‑T) and others] have been developed as investigational drugs...Phase III clinical trials of Rova‑T for patients with small‑cell lung cancer and a phase III clinical trial of nirogacestat for patients with desmoid tumors are ongoing. Integration of human intelligence, cognitive computing and explainable artificial intelligence is necessary to construct a Notch‑related knowledge‑base and optimize Notch‑targeted therapy for patients with cancer.