By Fineline Cube 
The National Medical Products Administration (NMPA) of China has published the “Guidance Principles for Clinical Trial Design of New Drugs for Advanced Gastric Cancer,” offering a comprehensive framework to optimize drug development and accelerate patient access to innovative treatments.
Key Components of the Guidance
1. Molecular Profiling and Biomarkers
The document highlights the importance of molecular subtyping in gastric cancer, emphasizing key biomarkers such as HER2, PD-L1, MSI status, and Claudin 18.2. Specifically:
- Approximately 12-13% of Chinese gastric cancer patients are HER2-positive.
- MSI-H/dMMR patients constitute 3-7% of advanced gastric cancer cases.
- PD-L1 high expression is associated with better responses to immunotherapy.
2. Exploratory Clinical Trial Design
The guidance encourages:
- Early single-agent trials in patients who have failed standard treatments.
- Innovative trial designs, including adaptive designs and basket/umbrella trials.
- Collection of detailed baseline data, including biomarker status and prior treatment history.
3. Registration-Critical Trials
The principles stress the importance of randomized controlled trials (RCTs), particularly with a superiority design. Key considerations include:
- Selection of appropriate control arms based on current standard treatments.
- Sufficient preclinical and early-phase data to support trial designs.
- Clear definitions of primary endpoints, with a focus on overall survival (OS).
4. Endpoint Considerations
While OS is the preferred primary endpoint for RCTs, the guidance allows for alternative endpoints under specific conditions:
- Objective response rate (ORR) and progression-free survival (PFS) can be used as co-primary endpoints in first-line studies if supported by robust data.
- For single-arm trials, ORR evaluated by an independent review committee (IRC) is recommended.
Conclusion
The guidelines underscore the unmet needs in advanced gastric cancer treatment and emphasize the importance of collaboration between researchers, clinicians, and regulators. By promoting innovative trial designs and biomarker-driven approaches, China aims to accelerate drug development and improve outcomes for patients with this challenging disease.-Fineline Info & Tech