P2, N=90, Active, not recruiting, Sanofi | Recruiting --> Active, not recruiting

P2, N=150, Recruiting, Sanofi | Trial completion date: Feb 2026 --> Feb 2028

P2, N=84, Recruiting, Sanofi | Not yet recruiting --> Recruiting

P1, N=40, Recruiting, Apogee Therapeutics, Inc. | Not yet recruiting --> Recruiting

P2/3, N=1310, Recruiting, Sanofi | Phase classification: P2 --> P2/3

P2, N=204, Recruiting, Sanofi | Not yet recruiting --> Recruiting

P2, N=204, Not yet recruiting, Sanofi

P1, N=120, Suspended, Sanofi-Aventis Australia Pty Ltd | Recruiting --> Suspended

P2, N=1310, Recruiting, Sanofi | N=450 --> 1310 | Trial completion date: Apr 2028 --> Dec 2028 | Trial primary completion date: Oct 2027 --> Dec 2028

Combining OX40L/PPT with PD-1 ICB significantly improved treatment efficacy in the CT26 subcutaneous colon cancer model, providing protective immunity against CT26 colon cancer cells. Overall, the anti-tumor efficacy observed with OX40L non-viral gene therapy, whether administered alone or in combination with ICB, highlights its potential to revolutionize cancer gene therapy, thus paving the way for unprecedented advancements in the cancer therapy field.

P2, N=84, Not yet recruiting, Sanofi

P2, N=150, Recruiting, Sanofi | Not yet recruiting --> Recruiting

P2, N=86, Active, not recruiting, Sanofi | Recruiting --> Active, not recruiting

P2, N=150, Not yet recruiting, Sanofi

P2, N=400, Recruiting, Scleroderma Research Foundation, Inc. | Not yet recruiting --> Recruiting

P3, N=961, Recruiting, Sanofi

P2, N=901, Recruiting, Sanofi | N=571 --> 901 | Trial completion date: Oct 2027 --> Oct 2028 | Trial primary completion date: Oct 2027 --> Oct 2028

Transcriptomic profiling reveals that OX40 and OX40L expression vary between and within tumor types, and that only ~ 17% of cancer patients have high OX40 and low OX40L, one of the expression patterns that might be theoretically amenable to OX40 agonist enhancement. Taken together, the data suggest that the OX40/OX40L machinery is a critical part of the immune stimulatory system and that understanding endogenous expression patterns of these molecules and co-existing checkpoints merits further investigation in the context of a precision immunotherapy strategy for cancer therapy.

P3, N=249, Recruiting, Sanofi | Not yet recruiting --> Recruiting

P2, N=390, Completed, Kymab Limited | Active, not recruiting --> Completed | Phase classification: P2b --> P2

P3, N=249, Not yet recruiting, Sanofi

P3, N=496, Recruiting, Sanofi

As the OX40 pathway is critical for expansion, differentiation, and survival of effector and memory T cells, its targeting might be a promising therapeutic approach to provide sustained inhibition of pathogenic T cells and associated inflammation and broad disease control. Antibodies against OX40 [rocatinlimab (AMG 451/KHK4083) and telazorlimab (GBR 830)] or OX40L [amlitelimab (KY1005)] have shown promising results in early-phase clinical studies of moderate-to-severe AD, highlighting the importance of OX40 signaling as a new therapeutic target in AD.

P3, N=420, Recruiting, Sanofi | Not yet recruiting --> Recruiting

P3, N=420, Not yet recruiting, Sanofi

P2, N=450, Recruiting, Sanofi | N=300 --> 450 | Trial completion date: Oct 2027 --> Apr 2028

P2, N=84, Recruiting, Sanofi | Not yet recruiting --> Recruiting

P2, N=446, Active, not recruiting, Sanofi | Recruiting --> Active, not recruiting

P2, N=380, Recruiting, Sanofi | Trial completion date: Jun 2030 --> Jun 2029 | Trial primary completion date: Jun 2030 --> Jun 2029

P3, N=420, Recruiting, Sanofi

P2, N=84, Not yet recruiting, Sanofi

P2, N=166, Recruiting, Sanofi | Not yet recruiting --> Recruiting

P2, N=380, Recruiting, Sanofi | Not yet recruiting --> Recruiting

In conclusion, the potential therapeutic effect of NK cells combined with Bev plus Iri against GBM cells was limited in this study. Accordingly, further research is required to improve the accessibility and strength of NK cell function in this combination treatment.

Co-culture of CD8 T cells expressing OX40 with IL-33-stimulated ILC2 expressing OX40L promoted cell activation and proliferation of CD8 T cells, which was significantly suppressed by administration of anti-OX40L blocking antibody. Thus, the IL-33-ILC2 axis promotes CD8 T cell responses via OX40/OX40L interaction and exerts an anti-tumor effect.

The resulting genetically engineered multifunctional immune-modulating exosomes (GEMINI-Exos) can not only redirect and activate T cells toward killing EGFR-positive triple negative breast cancer (TNBC) cells but also elicit robust anti-cancer immunity, giving rise to highly potent inhibition against established TNBC tumors in mice. GEMINI-Exos represent candidate agents for immunotherapy and may offer a general strategy for generating exosome-based immunotherapeutics with desired functions and properties.

Our findings suggest that the NK cells have a potent anti-tumor effect in combination with CRT against HNSCC.

OX40 and OX40L are abnormally expressed in the peripheral blood of patients with MG and may be closely associated with disease status and treatment. The OX40/OX40L pathway may be involved in the immunopathological process of MG and may play a role mainly in the later stage of MG.

This combination led to a greater than 90% cure rate of mice with metastatic lesions. Although the mechanisms by which inhibition of p38MAPKα shapes the metastatic tumor microenvironment are still under investigation, our findings indicate that metastatic breast cancer patients may benefit from immunotherapy when carried out in combination with p38i.

Anti-OX40 antibody and anti-OX40L antibody suppressed the proliferation of CTCL cell lines both in vitro and in vivo. These results suggest that OX40-OX40L interactions could contribute to the proliferation of MF/SS tumor cells and that the disruption of OX40-OX40L interactions could become a new therapeutic strategy for the treatment of MF/SS.

Collectively, this work highlighted the significance of OX40 and OX40L in prognosis and TME cell infiltration characterization of SCLC. Evaluating the OX40/OX40L-expression levels of individual patients with SCLC might contribute to guiding more precise therapy.

Moreover, compared to the NDV-treated group, the level of mouse IFN-γ protein in the tumor site increased significantly in the rNDV-mOX40L-treated group. Taken together, rNDV-mOX40L exhibited superior anti-tumor immunity by stimulating tumor-specific T cells and may be a promising agent for cancer immunotherapy.