TROP2 ADC: A Tale of Divergent Paths for Gilead, Hengrui, and More

The field of Antibody-Drug Conjugates (ADCs) has seen a surge in interest, with Trop2 ADCs gaining significant momentum. Recent developments from companies like Gilead, Hengrui Pharmaceuticals, Merck, and Daiichi Sankyo have brought forth advancements in Trop2 ADC research. However, these endeavors have taken different directions, leading to varied outcomes. Let's delve into the intriguing world of Trop2 ADCs and explore the distinct paths taken by different pharmaceutical companies.

Gilead's TROP2 ADC - Trodelvy:

Trodelvy, an ADC developed by Gilead, has garnered significant attention. It consists of Sacituzumab Govitecan, a novel antibody-drug conjugate that combines a humanized IgG1 antibody targeting the TROP-2 antigen with the metabolically active product SN-38 of the chemotherapeutic drug Irinotecan. TROP-2 is a cell surface glycoprotein expressed in over 90% of triple-negative breast cancer (TNBC). Trodelvy became the first globally approved Trop2 ADC when it received accelerated FDA approval in April 2020 for the treatment of metastatic TNBC in patients who have received at least two prior therapies. Despite this success, Trodelvy faced a setback in a Phase III trial (Evoke-01) on January 22, 2024, where it failed to meet the overall survival endpoint in previously treated patients with metastatic non-small cell lung cancer (NSCLC). This outcome raised questions about Trodelvy's efficacy as a later-line treatment for NSCLC.

Hengrui's SHR-A1921:

On the other hand, Hengrui Pharmaceuticals has brought positive news with their Trop2 ADC candidate named SHR-A1921. In a Phase I trial, SHR-A1921 demonstrated an objective response rate of 33.3% and a disease control rate of 80% in solid tumors. Hengrui has registered a Phase II/III clinical trial to evaluate the efficacy and safety of SHR-A1921 compared to platinum-based double chemotherapy in patients with recurrent epithelial ovarian cancer. This marks an optimistic development for Hengrui Pharmaceuticals as they venture into the ovarian cancer indication with their Trop2 ADC.

Other Trop2 ADCs:

Aside from Gilead and Hengrui, notable Trop2 ADCs include DS-1062, a collaboration between AstraZeneca and Daiichi Sankyo, and SKB264 developed by Karonbio. DS-1062 faced a setback when it failed to meet the statistical significance for overall survival improvement in a Phase III trial for advanced NSCLC. However, it showed promising results in the treatment of HR+/HER2- breast cancer. Meanwhile, SKB264, developed by Karonbio, has submitted a marketing application in China for the treatment of advanced triple-negative breast cancer in the third-line setting.

The development of Trop2 ADCs has witnessed divergent paths for different pharmaceutical companies. While Gilead faced a setback with Trodelvy in NSCLC, Hengrui's SHR-A1921 and other candidates like DS-1062 and SKB264 continue to show promise in various indications. The key lies in selecting the right indications for these therapies. As the Trop2 ADC landscape evolves, further advancements and challenges are expected, shaping the future of targeted cancer therapies.