Table of Contents

• Overview of the Clinical Trial
• Target Population and C797S Mutation
• Trial Design and Methodology
• Phase 2 Objectives and Endpoints
• Patient Enrollment and Eligibility
• Clinical Significance

Overview of the Clinical Trial

A Phase 2 clinical trial is currently investigating WSD0922-FU, also known by its chemical name (R)-6-((3,3-DIFLUORO-1-METHYLPIPERIDIN-4-YL)OXY)-N-(3-ETHYNYL-2-FLUOROPHENYL)-7-METHOXYQUINAZOLIN-4-AMINE-FUMARATE (2:1), for the treatment of patients with non-small cell lung cancer (NSCLC) who have developed a specific genetic mutation known as C797S^[1]. This trial represents an important step in developing targeted therapies for patients whose cancer has developed resistance to existing treatments.

The study is registered under the identifier 2024-519713-65-00 and has received authorization to proceed^[1]. As an interventional study, this trial involves actively administering the investigational drug WSD0922-FU to participants and measuring the effects on their cancer. The trial follows a single-arm design, meaning all enrolled patients will receive the same treatment rather than being randomly assigned to different treatment groups or a placebo.

Target Population and C797S Mutation

This clinical trial specifically targets patients diagnosed with non-small cell lung cancer who harbor the C797S mutation^[1]. Understanding this target population is crucial for appreciating the importance of this research.

Non-small cell lung cancer is the most common form of lung cancer, accounting for approximately 85% of all lung cancer diagnoses. Within NSCLC, there are several subtypes, and many patients have tumors driven by specific genetic mutations that can be targeted with specialized therapies.

The C797S mutation is particularly significant because it represents a mechanism of acquired resistance to certain lung cancer treatments. This mutation can develop in cancer cells after initial treatment with targeted therapies, particularly those that target the epidermal growth factor receptor (EGFR). When this mutation occurs, cancer cells can continue to grow despite treatment, creating a need for new therapeutic approaches that can overcome this resistance mechanism.

Patients eligible for this trial must have documented evidence of the C797S mutation in their tumor tissue. This requirement ensures that the study population consists of individuals most likely to benefit from WSD0922-FU if it proves effective against this specific resistance mutation.

Trial Design and Methodology

The trial is designed as a single-arm study, which means all participants will receive WSD0922-FU rather than being divided into groups receiving different treatments or placebo^[1]. This design is appropriate for Phase 2 trials investigating treatments for specific genetic mutations where there may be limited alternative options.

As an interventional study, researchers will actively administer WSD0922-FU to participants according to a specific protocol^[1]. The trial will carefully monitor patients throughout treatment to collect data on both effectiveness and safety. This monitoring includes regular imaging studies to assess tumor response, blood tests to evaluate safety parameters, and clinical assessments to track symptoms and side effects.

The study methodology incorporates standardized response assessment using RECIST version 1.1 (Response Evaluation Criteria in Solid Tumors)^[1]. This internationally recognized system provides consistent criteria for measuring whether tumors are responding to treatment, remaining stable, or progressing. RECIST v1.1 uses specific measurements of tumor size from imaging studies to categorize patient responses into defined categories.

Phase 2 Objectives and Endpoints

This Phase 2 trial has two primary objectives that will determine whether WSD0922-FU should advance to further clinical development^[1].

The first objective is to determine the recommended Phase 2 dose (RP2D) of WSD0922-FU^[1]. While Phase 1 trials typically establish initial safety and dosing information, Phase 2 studies refine this knowledge by confirming the optimal dose that balances effectiveness with acceptable side effects in the target patient population. The RP2D represents the dose that will be used in future studies if the drug continues development.

The second primary objective is to assess the efficacy of WSD0922-FU by measuring the Objective Response Rate (ORR)^[1]. The ORR is a key measure in cancer clinical trials that indicates the percentage of patients whose tumors either shrink significantly (partial response) or disappear completely (complete response) during treatment. This endpoint provides direct evidence of whether the drug has meaningful anti-cancer activity.

The trial will use RECIST v1.1 criteria to evaluate tumor response^[1]. Under these criteria, responses are categorized as:

• Complete Response (CR): Disappearance of all target lesions and cancer-related symptoms
• Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions
• Stable Disease (SD): Neither sufficient shrinkage to qualify as PR nor sufficient growth to qualify as progressive disease
• Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions or appearance of new lesions

The ORR includes patients who achieve either complete or partial responses, providing a clear measure of the drug’s anti-tumor activity in this specific patient population.

Patient Enrollment and Eligibility

The trial plans to enroll approximately 40 patients with NSCLC who have the C797S mutation^[1]. This sample size is typical for Phase 2 trials and is designed to provide sufficient data to assess the drug’s effectiveness while limiting exposure to an investigational treatment until more is known about its benefits and risks.

While the available trial information specifies that participants must have NSCLC with the C797S mutation, Phase 2 trials typically include additional eligibility criteria that may include:

• Confirmed diagnosis of non-small cell lung cancer through biopsy
• Documented presence of the C797S mutation through genetic testing
• Measurable disease that can be evaluated using RECIST criteria
• Previous treatment history, particularly with EGFR-targeted therapies
• Adequate organ function to tolerate the investigational treatment
• Performance status indicating ability to participate in the trial

The enrollment of 40 patients represents a focused approach to studying this treatment in a well-defined population. This number allows researchers to gather meaningful data about response rates while maintaining statistical validity for the primary endpoints.

Clinical Significance

This clinical trial addresses an important unmet medical need in the treatment of non-small cell lung cancer. The development of the C797S mutation represents a significant challenge in managing NSCLC, as it confers resistance to therapies that may have initially been effective. Patients who develop this resistance mutation have limited treatment options, making the investigation of new targeted therapies like WSD0922-FU particularly valuable.

The trial’s focus on a specific genetic mutation exemplifies the principles of precision medicine in cancer treatment. Rather than treating all NSCLC patients the same way, this approach recognizes that different genetic changes in tumors may require different therapeutic strategies. By targeting the C797S mutation specifically, WSD0922-FU may offer benefits to patients whose tumors have this particular resistance mechanism.

The Phase 2 designation indicates that WSD0922-FU has already undergone initial safety testing in Phase 1 trials^[1]. The current study builds on that foundation by evaluating effectiveness in the intended patient population. Success in this Phase 2 trial, demonstrated by an acceptable safety profile and meaningful objective response rate, would support further development of WSD0922-FU in larger Phase 3 trials.

The authorized status of the trial indicates that regulatory authorities have reviewed and approved the study protocol^[1]. This authorization means that the trial design, patient protections, and scientific rationale have met regulatory standards, allowing patient enrollment and treatment to proceed.

For patients with NSCLC and the C797S mutation, this trial represents a potential new treatment option. While participation in clinical trials always involves uncertainty about outcomes, trials like this one are essential for advancing cancer treatment and may provide access to promising new therapies before they become widely available.