JS108

JS108 is a recombinant humanized anti-TROP2 monoclonal antibody-Tub196 conjugate developed as an antibody-drug conjugate (ADC) for the treatment of solid tumors. Based on the search results, I can provide the following comprehensive information about this drug. ## Drug Profile JS108 is an antibody-drug conjugate that targets TROP2 (trophoblast cell-surface antigen 2), a transmembrane glycoprotein highly expressed in various solid tumors including breast cancer, gastric cancer, non-small cell lung cancer, small cell lung cancer, colon cancer, and pancreatic cancer[1][2]. The drug consists of a humanized anti-TROP2 monoclonal antibody conjugated with Tub196, which is an antitubulin Tubulysin B analog[1]. This conjugation occurs through a smart linker system that allows for targeted delivery of the cytotoxic payload to cancer cells[1]. ## Development History JS108 was developed through a collaboration between Hangzhou DAC Biotech and Shanghai Junshi Biosciences[1][2]. In July 2020, the clinical trial application for JS108 was approved by the National Medical Products Administration (NMPA) in China[2][6]. The first patient was dosed in a Phase I clinical study (NCT04601285) in December 2020[2][3]. The Phase I clinical trial was designed as an open-label, first-in-human study to evaluate the safety, tolerability, pharmacokinetic profile, and efficacy of JS108 in patients with advanced solid tumors[2][3]. The study consisted of three stages: dose escalation, dose expansion, and indication expansion, with planned enrollments of 16-36, 12-27, and 60-90 patients with advanced solid tumors, respectively[2][3]. However, according to the search results, the trial was terminated in June 2023 after enrolling 25 patients instead of the planned 153, as the sponsor adjusted its development plan[4]. ## Mechanism of Action As an antibody-drug conjugate, JS108 works by targeting TROP2, which is implicated in promoting tumor cell proliferation, tissue invasion, and metastasis[2][6]. The overexpression of TROP2 has been correlated with poor clinical prognosis in various cancers[2][6]. Unlike non-specific chemotherapy, ADCs like JS108 are designed to target and kill tumor cells while sparing normal healthy cells[2][6]. The antibody component binds specifically to TROP2 on cancer cells, after which the conjugate is internalized, releasing the cytotoxic Tub196 payload that disrupts microtubule function, leading to cell death[1][4]. ## Current Status As of January 2025, JS108 was reported to be in Phase I clinical trials for solid tumors according to the Shanghai Junshi Biosciences pipeline[1]. However, it's important to note that the original Phase I trial (NCT04601285) was terminated in June 2023[4], suggesting that the development strategy for this drug may have been revised. ## Comparison to Other TROP2-Targeted ADCs JS108 is part of a growing class of TROP2-targeted ADCs being developed for solid tumors. Other notable drugs in this class include: 1. Sacituzumab govitecan (Trodelvy) - Already approved for triple-negative breast cancer (TNBC) and urothelial carcinoma 2. Datopotamab deruxtecan (Dato-DXd) - In Phase III trials for multiple indications 3. SKB-264 - In Phase III trials for various cancers 4. BIO-106 - In Phase I/II trials for solid tumors[5] Each of these ADCs has unique characteristics in terms of antibody structure, linker technology, and cytotoxic payload, which may affect their efficacy and safety profiles in different cancer types.

Other names

anti-TROP2 monoclonal antibody-Tub196 conjugate JS108anti-TROP-2 monoclonal antibody-Tub196 conjugate JS108anti-TROP 2 monoclonal antibody-Tub196 conjugate JS108ADC JS108anti-Trop-2 antibody-drug conjugate JS108anti-Trop2 antibody-drug conjugate JS108anti-Trop 2 antibody-drug conjugate JS108anti-TROP2 ADC JS108anti-TROP-2 ADC JS108anti-TROP 2 ADC JS108anti-TROP2-Tub196 ADC JS108anti-TROP-2-Tub196 ADC JS108anti-TROP 2-Tub196 ADC JS108