P1, N=97, Active, not recruiting, GlaxoSmithKline | Trial completion date: Mar 2025 --> Mar 2026

To address these limitations, we have engineered cationic quaternary ammonium salt-based drug-eluting microspheres capable of loading 131I and ADU-S100...This approach effectively overcomes the current limitations of poor embolic efficacy and non-target embolization associated with radioactive microspheres. Moreover, it activates the tumor immune microenvironment, addressing the issue of tumor immune resistance and further improving therapeutic outcomes, thereby showing great clinical application potential.

Activation of STING pathway by ADU-S100 enhances the antitumor efficacy of doxorubicin in STS. Combining doxorubicin with STING agonists may be a promising therapeutic strategy worth exploring in future clinical trials.

In HCC models with liver fibrosis in male mice, anti-PD-1 ICB or the STING agonist BMS-986301 increase intratumoral B-cell infiltration, circulating IL-10, and TIM-1+ B-cells, promoting tertiary lymphoid structure formation...In addition, co-targeting STING and TIM-1 enhances B-cell differentiation and antigen presentation, reduces intratumoral TIM-1+ B-cells, and increases CD86 and MHC class II expression, thereby augmenting CD8+ T-cell-mediated anti-tumor immunity. These findings reveal that B-cells contribute to ICB and STING therapy resistance in HCC, and that B-cell depletion or TIM-1 blockade can overcome acquired resistance to these immunotherapies.

P1, N=70, Recruiting, Daiichi Sankyo | Not yet recruiting --> Recruiting

Dazostinag, combined with pembrolizumab after radiotherapy, was well tolerated and demonstrated clinical activity in some patients with advanced/metastatic tumors whose disease had progressed on CPIs.

P1, N=21, Completed, Sichuan Kelun Pharmaceutical Research Institute Co., Ltd. | Recruiting --> Completed | N=30 --> 21

P1, N=6, Completed, Sichuan Kelun Pharmaceutical Research Institute Co., Ltd. | Recruiting --> Completed | N=30 --> 6

Candidates such as ADU-S100 and MSA-2 demonstrate enhanced STING activation and clinical potential...Future directions emphasize the development of smart nanocarriers with spatiotemporal control, biomarker-driven patient stratification, and combinatorial regimens that integrate epigenetic or metabolic modulators. This review underscores the transformative potential of cGAS-STING-targeted therapies while outlining critical hurdles and interdisciplinary strategies to advance precision cancer immunotherapy.

The stochastic cysteine conjugation of the dazostinag containing these linkers provided ADC TAK-500 and its mouse surrogate mTAK-500 with DAR = 4. In syngeneic tumor-bearing mouse models, mTAK-500 showed target specific antitumor activity as well as the induction of immune-stimulating cytokines.

NanoSTING@Mn, composed of ADU-S100 complexed with Mn2⁺ and encapsulated in biomimetic liposomes, potently activates the cGAS-STING pathway, induces a type I interferon response, and promotes lymphocyte infiltration...Upon intravenous rechallenge, disseminated tumor cells are eliminated, preventing metastasis and ensuring long-term protection. This synergistic approach offers a scalable platform to boost immunotherapy efficacy and redefines immune-based metastasis prevention strategies.

P1, N=10, Terminated, Actym Therapeutics, Inc. | N=35 --> 10 | Trial completion date: Jul 2026 --> Aug 2025 | Recruiting --> Terminated | Trial primary completion date: Jan 2026 --> Aug 2025; Sponsor's strategic business decision