This trial will study SGN-CD228A to find out whether it is an effective treatment for different kinds of cancer. It will also look at what side effects (unwanted effects) may occur. The study will have two parts. Part 1 of the study will find out how much SGN-CD228A should be given for treatment and how often. Part 2 of the study will use the dose found in Part 1 and look at how safe and effective the treatment is.

Start Date03 Sep 2019

Sponsor / Collaborator

Seagen, Inc.

100 Clinical Results associated with SGN-CD228A

100 Translational Medicine associated with SGN-CD228A

100 Patents (Medical) associated with SGN-CD228A

563

Literatures (Medical) associated with SGN-CD228A

01 Apr 2025·Bioorganic & Medicinal Chemistry

Fine-tuning phenoxy silyl scaffolds for the development of glutathione-responsive prodrugs and antibody–drug conjugates

Article

Author: Jiang, Yuecheng ; Wang, Huihui ; Huangfu, Shangwei ; Jiang, Biao ; Chen, Hongli ; Wei, Ding ; Qi, Cheng ; Yu, Xianqiang

Silyl ether is particularly attractive for application in drug development for its easy preparation, non-toxicity and remarkable biocompatibility. Earlier studies relied on the use of intracellular acidic conditions to induce the cleavage of alkoxy silyl ethers. However, acidic conditions are not suitable to trigger the release of phenoxy silyl ethers, since they are more stable under acidic conditions compared with neutral conditions. We explored the vulnerability of the phenoxy silyl ether towards biological nucleophilic reagents and found that glutathione (GSH) could effectively and selectively induce the cleavage of phenoxy silyl ether. We also demonstrated that the rate of cleavage was controllable by adjusting the substituents on the phenyl ring. Phenoxy silyl ether-based prodrugs and antibody-drug conjugates (ADCs) were designed and synthesized, which could be effectively activated in cells with high GSH levels and there was an obvious therapeutic window between cells with different GSH levels.

19 Feb 2025·Bioconjugate Chemistry

A Unique Prodrug Targeting the Prostate-Specific Membrane Antigen for the Delivery of Monomethyl Auristatin E

Article

Author: Berkman, Clifford E. ; Savoy, Emily A. ; Bomba, Hunter N. ; Fulton, Melody D. ; Langton-Webster, Beatrice

Monomethyl auristatin E (MMAE) is a promising treatment option for patients diagnosed with prostate cancer (PCa); however, toxicities prevent MMAE from being administered as free drug. No MMAE-based treatment is currently marketed for PCa. Herein, we describe a small-molecule-drug conjugate, CTT2274, for the selective delivery of MMAE. CTT2274 is composed of a prostate-specific membrane antigen (PSMA)-binding scaffold, a biphenyl motif, a pH-sensitive phosphoramidate linker, and MMAE payload. We demonstrate that CTT2274 shows selective binding to PSMA, which is overexpressed on PCa cells, and induces tumor cell death in vitro. In a patient-derived xenograft tumor model of PCa in mice, we show that weekly intravenous dosing of CTT2274 at 3.6 mg/kg for six weeks is superior to treatment with free MMAE at equivalent doses. Mice treated with CTT2274 experienced prolonged tumor suppression and significantly greater overall survival than mice treated with PBS. Additionally, the safety of CTT2274 compared to an equivalent dose of MMAE was assessed in healthy, non-tumor-bearing mice. Our results demonstrate that CTT2274 therapy is as efficacious as MMAE, results in superior overall survival, and has a more favorable safety profile. Together, these data indicate that CTT2274 is a candidate for clinical translation for the treatment of PCa.

18 Feb 2025·ACS Nano

Nanobody-Mediated Cellular Uptake Maximizes the Potency of Polylysine Dendrimers While Preserving Solid Tumor Penetration

Article

Author: Feeney, Orlagh M. ; Johnston, Angus P.R. ; Humphries, James ; Noi, Leo ; Owen, David J. ; Porter, Christopher J.H. ; Cullinane, Carleen ; Fletcher, Nicholas L. ; Yuen, Daniel ; Houston, Zachary H ; Thurecht, Kristofer J. ; Reitano, Pauline ; Hufton, Richard ; McLeod, Victoria M. ; Shengule, Sudhir ; Tsegay, Sammi

Dendrimers are branched macromolecular structures that are useful nanocarriers for small-molecule drugs, such as cancer therapeutics. Their small size permits penetration into solid tumors, coupled with functionalization with a low-fouling PEG coating that minimizes transient cellular interactions and enhances plasma circulation time. While PEGylated dendrimers show significant promise as anticancer therapeutics, there is potential to increase tumor cell specificity and drive uptake of drugs into cells by conjugating cell-targeting ligands onto the dendrimers. To achieve this, we used an expanded genetic code and bio-orthogonal click chemistry to functionalize monomethyl auristatin E (MMAE)-loaded PEGylated dendrimers with a single tumor cell-targeting nanobody per dendrimer. The uniform addition of a single nanobody ligand facilitated greater intracellular uptake of the drug payload into HER2-positive target cells, while preserving the desirable circulatory characteristics of dendrimers. While the nanobody-dendrimer conjugates show similar levels of tumor infiltration over 24 h compared to unmodified dendrimers, the targeted dendrimers had significantly greater inhibition of tumor growth and long-term retention in the tumors. Our results highlight that biodistribution studies alone are poor predictors of therapeutic performance. The controlled conjugation strategy presented here preserves the size advantage and tissue penetration of dendrimers while maximizing targeted cellular uptake and potency in difficult-to-access solid tumor tissue.

100 Deals associated with SGN-CD228A

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
HER2-negative breast cancer	Phase 1	Spain	Seagen, Inc.	03 Sep 2019
HER2-negative breast cancer	Phase 1	France	Seagen, Inc.	03 Sep 2019
HER2-negative breast cancer	Phase 1	United Kingdom	Seagen, Inc.	03 Sep 2019
HER2-negative breast cancer	Phase 1	United States	Seagen, Inc.	03 Sep 2019
HER2-negative breast cancer	Phase 1	Italy	Seagen, Inc.	03 Sep 2019
Pancreatic Ductal Adenocarcinoma	Phase 1	Spain	Seagen, Inc.	03 Sep 2019
Pancreatic Ductal Adenocarcinoma	Phase 1	United Kingdom	Seagen, Inc.	03 Sep 2019
Pancreatic Ductal Adenocarcinoma	Phase 1	France	Seagen, Inc.	03 Sep 2019
Pancreatic Ductal Adenocarcinoma	Phase 1	United States	Seagen, Inc.	03 Sep 2019
Pancreatic Ductal Adenocarcinoma	Phase 1	Italy	Seagen, Inc.	03 Sep 2019

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