The "Phase I/II Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of ESG401 in Patients with Locally Advanced/Metastatic Solid Tumors" (Study Number: ESG401-101), sponsored by Shanghai Escugen Biotechnology Co., Ltd., has been successfully launched. The study has received approval from the National Medical Products Administration (Clinical Trial Notification Number: 2021LP01074) and is currently recruiting participants at multiple top-tier hospitals across the country.

Drug Introduction

ESG401 is an antibody-drug conjugate (ADC) targeting trophoblast cell-surface antigen 2 (Trop2). ADCs, often referred to as "magic bullets," consist of three components: a monoclonal antibody (mAb), a linker, and a cytotoxic small molecule (payload). They represent a fusion of targeted therapy and chemotherapy, delivering targeted strikes on cancer cells with precision.

ADCs link biologically active small molecules to monoclonal antibodies via a chemical linker. The antibody serves as a carrier, transporting the cytotoxic small molecule to the target cells. ADCs combine the high antitumor efficacy of cytotoxic small molecules with the high selectivity, stability, and favorable pharmacokinetic properties of monoclonal antibodies, making them a hot research topic in the field of oncology.

The antibody component of Escugen's ESG401 is a humanized IgG1 targeting Trop2, and the small molecule SN-38 is the active metabolite of the topoisomerase I inhibitor irinotecan.

Trop2, a member of the TACSTD family, is a cell surface glycoprotein encoded by the TACSTD2 gene, also known as tumor-associated calcium signal transducer 2 (TACSTD2), epiglycanin-1 (EGP-1), gastrointestinal tumor-associated antigen (GA733-1), or surface marker 1 (M1S1).

Recent studies have shown that Trop2 is one of the genes closely related to tumors. Trop2 is expressed at low levels in normal tissues but is highly expressed in various tumors, including breast cancer, lung cancer, gastric cancer, colorectal cancer, pancreatic cancer, prostate cancer, cervical cancer, head and neck cancer, and ovarian cancer. The overexpression of Trop2 plays a key role in tumor growth, regulating signaling molecules involved in tumor cell growth, primarily through modulating calcium signaling pathways, cyclin expression, and reducing fibronectin adhesion, thereby promoting tumor cell growth, proliferation, and metastasis. Trop2 is expressed on the surface of over 80% of triple-negative breast cancer (TNBC) cells and is associated with more aggressive disease and poor prognosis. High Trop2 expression is found in 64% of non-small cell adenocarcinomas and 75% of non-small cell squamous cell carcinomas, and its overexpression is closely related to poor prognosis in non-small cell lung cancer (NSCLC). Compared to normal tissues, Trop2 expression is higher in non-invasive bladder cancer (papillary urothelial carcinoma), and its expression is positively correlated with disease severity. Therefore, Trop2 has become an ideal therapeutic target, with several Trop2-targeted ADCs demonstrating good antitumor efficacy in the clinical treatment of solid tumors.

ESG401-101 Participant Recruitment

Key Inclusion Criteria:

•Willing and able to provide written informed consent.

•Male or female, aged 18-75 years (inclusive).

•Histologically or cytologically confirmed advanced or metastatic solid tumors with no effective standard treatment or intolerance to standard treatment.

Notes:

1）Participants in Cohort 1, Cohort 2, and Cohort 3 of Phase Ib and Phase II TNBC must have progressed or relapsed after receiving 2 or more (up to 4) lines of standard treatment.

2）Participants in Cohort 4 and Cohort 5 of Phase Ib must be patients with locally advanced or metastatic HR+/HER2- breast cancer who have progressed during endocrine therapy or are not suitable for endocrine therapy and have received 1-2 lines of chemotherapy in the unresectable/metastatic setting.

3）Participants in Cohort 6 of Phase Ib must be patients with locally advanced or metastatic TNBC who have not received systemic treatment for unresectable/metastatic disease.

•At least one measurable lesion (according to RECIST 1.1 criteria).

•Adequate organ function.

Participant Benefits:

•Free treatment drugs provided by the sponsor.

•Free laboratory and related examinations.

•Transportation subsidies or nutritional allowances for each visit.

Research Centers:

For more information about this study, please contact the research center staff. The doctors will provide you with a detailed introduction to the study.