SHR-A1904: A Phase 1 Trial of an Antibody-Drug Conjugate Targeting CLDN18.2 in Advanced Gastric and Gastroesophageal Junction Cancers

Breakthrough Cancer Therapy Trial Shows Promising Results in China

Shanghai, China – A critically important clinical trial conducted across multiple institutions in China has yielded encouraging results for a novel digestive oncology treatment. The study, involving a comprehensive team of researchers and clinicians, investigated the efficacy and safety of a new therapeutic approach targeting digestive cancers.

The trial, which included contributions from leading medical centers such as the First Affiliated Hospital of Henan University of Science & Technology in Luoyang, the Cancer Hospital affiliated to Guangxi Medical University in Nanning, and the First Affiliated Hospital of Nanchang University, aimed to advance treatment options for patients battling these challenging diseases. Researchers from Jiangsu Hengrui Pharmaceuticals Co., Ltd., a key player in pharmaceutical innovation, were instrumental in the study’s design and execution, with significant input from departments in Shanghai.

While specific treatment details remain within the published study’s scope, the collaborative effort underscores a critical trend in modern cancer research: a multi-disciplinary approach yielding robust data.The data analysis, spearheaded by biometrics experts, suggests a positive impact, paving the way for further examination and potential clinical adoption.

Evergreen Insight: This study highlights the power of collaboration and dedicated research in the fight against cancer. As medical science progresses, comprehensive trials like this, involving diverse patient populations and expert analysis, are crucial for developing effective and safe treatments. The commitment shown by the participating institutions and the pharmaceutical industry signifies a shared dedication to improving oncological care. The rigorous process of data acquisition, analysis, and critical review by a broad group of authors ensures the scientific integrity and potential impact of findings. Ultimately, such advancements offer hope and pave the path towards better outcomes for cancer patients worldwide.

What IHC cut-off values are being investigated to identify patients most likely to respond to SHR-A1904 treatment?

SHR-A1904: A Phase 1 Trial of an Antibody-Drug Conjugate Targeting CLDN18.2 in Advanced Gastric adn Gastroesophageal junction Cancers

Understanding CLDN18.2 and its role in Cancer

Claudin 18.2 (CLDN18.2) is a protein highly expressed in various cancers, most notably gastric cancer, gastroesophageal junction (GEJ) cancer, and pancreatic cancer. Its limited expression in normal tissues makes it an attractive target for cancer-specific therapies. This is where Antibody-Drug Conjugates (ADCs) come into play, offering a targeted approach to deliver potent cytotoxic agents directly to cancer cells, minimizing damage to healthy tissue. Targeting CLDN18.2 represents a promising avenue for improving treatment outcomes in these challenging cancers.Research into CLDN18.2 expression is crucial for patient selection and predicting response to therapies.

What is SHR-A1904?

SHR-A1904 is an investigational ADC designed to specifically target CLDN18.2. It consists of an anti-CLDN18.2 antibody linked to a cytotoxic payload – a chemotherapy drug. The antibody acts as a homing device,delivering the payload directly into cancer cells that express CLDN18.2. This targeted delivery aims to maximize efficacy while reducing systemic toxicity, a common issue with customary chemotherapy. Antibody-drug conjugates are revolutionizing cancer treatment by offering this precision.

Phase 1 Trial Design and Objectives

The Phase 1 trial of SHR-A1904, as of July 16, 2025, is focused on evaluating the safety, tolerability, and preliminary efficacy of the ADC in patients with advanced gastric and GEJ cancers. Key aspects of the trial include:

dose Escalation: The trial employs a standard dose-escalation scheme, starting with a low dose of SHR-A1904 and gradually increasing it to determine the maximum tolerated dose (MTD).

Patient Population: The study enrolls patients with locally advanced or metastatic gastric or GEJ adenocarcinoma who have progressed after prior standard therapies. Gastric cancer treatment options are frequently enough limited in advanced stages, making trials like this vital.

Primary Endpoint: The primary endpoint is to determine the MTD and dose-limiting toxicities (DLTs).

Secondary Endpoints: Secondary endpoints include objective response rate (ORR), progression-free survival (PFS), duration of response (DOR), and overall survival (OS). Progression-free survival is a key indicator of treatment effectiveness.

Biomarker Analysis: Researchers are also analyzing biomarkers,including CLDN18.2 expression levels, to identify potential predictors of response to SHR-A1904.Biomarker testing is becoming increasingly important in personalized cancer medicine.

Preliminary Data and Key Findings (as of July 16, 2025)

While full results are still pending, preliminary data presented at recent oncology conferences (e.g., ASCO, ESMO) suggest:

Safety Profile: SHR-A1904 appears to be generally well-tolerated at lower doses. Common adverse events observed include fatigue, nausea, and infusion-related reactions. More serious adverse events,possibly related to the cytotoxic payload,have been observed at higher doses.

early Efficacy Signals: Initial data indicate some evidence of anti-tumor activity in patients with high CLDN18.2 expression. Several patients have experienced stable disease, and a few have shown partial responses. Tumor response is carefully monitored throughout the trial.

CLDN18.2 Correlation: A trend towards greater efficacy is observed in patients with higher levels of CLDN18.2 expression, reinforcing the importance of biomarker selection.

The Role of Biomarkers in Patient Selection

Identifying patients most likely to benefit from SHR-A1904 is crucial. CLDN18.2 expression is assessed using immunohistochemistry (IHC) on tumor samples.

IHC Scoring: A standardized IHC scoring system is used to determine the level of CLDN18.2 expression.

Cut-off Values: Researchers are investigating optimal cut-off values for CLDN18.2 expression to identify patients who are most likely to respond to treatment.

Companion Diagnostic: The development of a companion diagnostic test to accurately assess CLDN18.2 expression could be essential for guiding treatment decisions. Companion diagnostics are increasingly used to personalize cancer therapy.

Future Directions and Clinical Development

Based on the Phase 1 data, the development of SHR-A1904 is expected to proceed to Phase 2 trials. These trials will likely:

Expand Patient Population: Include a larger number of patients with advanced gastric and GEJ cancers.

* Investigate Combination Therapies: Evaluate SHR-A1904 in combination with other cancer treatments, such as chemotherapy