WSD0922-FU plus osimertinib for EGFR-mutant advanced NSCLC with C797S or new brain metastases

A Phase I/II Study to Evaluate Safety, Tolerability, Pharmacokinetics and Anti-tumor Activity of WSD0922-FU in Combination With Osimertinib for Patients With Locally Advanced or Metastatic Non- Small Cell Lung Cancer

This trial will test whether adding WSD0922-FU to osimertinib helps adults with advanced EGFR-mutant NSCLC who have the C797S resistance mutation or newly diagnosed brain metastases.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 48 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Wayshine Biopharm, Inc. (Industry-sponsored)
• Drugs / interventions: chemotherapy, immunotherapy, Osimertinib
• Locations: 1 site (Shanghai)
• Trial ID: NCT07206498 on ClinicalTrials.gov

What this trial studies

This open-label Phase 1/2 trial combines WSD0922-FU, a reversible inhibitor active against EGFR with C797S, with the third-generation EGFR inhibitor osimertinib to characterize safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity. Phase 1 will determine dose and safety while Phase 2 will further explore efficacy, including in patients with newly diagnosed CNS metastases carrying classical EGFR Del19 or L858R mutations. Eligible participants must have measurable disease per RECIST 1.1, ECOG performance status 0–1, and adequate organ function, with mandatory blood/tissue sampling. Outcomes will include adverse events, PK measures, and objective response in target lesions.

Who should consider this trial

Good fit: Adults (≥18) with locally advanced or metastatic EGFR-mutant NSCLC who have progressed on third-generation EGFR-TKI with a C797S mutation or who are newly diagnosed with CNS metastases and have Del19 or L858R mutations, ECOG 0–1, measurable disease, and adequate organ function are ideal candidates.

Not a fit: Patients with poor performance status, inadequate organ function, or who have recently received other anti-cancer therapies may not be eligible or likely to benefit from this combination.

Why it matters

Potential benefit: If successful, the combination could help overcome C797S-mediated resistance and better control brain metastases in a subset of EGFR-mutant NSCLC patients.

How similar studies have performed: Related strategies targeting C797S-mediated resistance and combining novel EGFR-targeting agents with osimertinib have shown preclinical promise and some early-phase signals, but the WSD0922-FU plus osimertinib combination is novel and not yet proven in patients.

Eligibility criteria

Inclusion Criteria:

* ≥Age 18, gender is not limited;
* Locally advanced or metastatic NSCLC confirmed by pathology;
* Patients who have been genetically tested to carry EGFR sensitive mutations;
* Blood/Tissue samples must be provided for testing;
* Must have a minimum life expectancy of \>= 3 months;
* At least one measurable tumor lesion according to RECIST version 1.1; ● Previous radiotherapy-treated lesions cannot be used as target lesions unless imaging studies show clear progression of the lesions.
* Physical Status (ECOG PS) score was 0-1;
* Have full organ function;
* Eligible patients (male and female) who are fertile must agree to use a reliable contraceptive method ;
* Subjects are required to give informed consent to this study before the experiment and sign a written informed consent voluntarily.

Exclusion Criteria:

* Received chemotherapy, radiotherapy, biological therapy, targeted therapy, endocrine therapy, immunotherapy, or other anti-tumor drug treatments within 4 weeks before the first administration of the study drug.
* Have previously received more than two EGFR-TKI inhibitors for part A;
* Received major organ surgery (excluding puncture biopsy) or significant trauma within 4 weeks before the first administration, or require elective surgery during the trial period.
* Used strong CYP3A4 inhibitors or strong CYP3A4 inducers within 7 days before the first use of the study drugs.
* Adverse reactions from previous anti-tumor treatments have not recovered to NCI-CTCAE v5.0 grade ≤1 (except for toxicities judged by the researcher to have no safety risks, such as hair loss, grade 2 peripheral neurotoxicity, and stable thyroid function after hormone replacement therapy).
* Skin/pressure ulcers, chronic leg ulcers, known active gastric ulcers, or non-healing wounds.
* History of severe allergies, or allergies to any active or inactive ingredients of the study drug;
* Severe infections requiring intravenous antibiotic infusion or hospitalization at the time of screening; or uncontrollable active infections within 4 weeks before administration;
* Known active or suspected autoimmune diseases; or known active ocular diseases (such as active wet age-related macular degeneration, diabetic retinopathy with macular edema);
* Human immunodeficiency virus (HIV) (HIV1/2 antibody) positive, syphilis spirochete antibody positive .
* Patients with interstitial lung disease.
* History of severe cardiovascular diseases.
* Unable to orally swallow medication, or there is a condition that significantly affects gastrointestinal absorption as judged by the researcher; Clinical intervention is required for pleural effusion, ascites (excluding subjects who do not need drainage and have been stable for more than 2 weeks after drainage).
* Known alcohol or drug dependence.
* Mental disorders or poor compliance;
* Pregnant or lactating women;
* The investigator believes that the subject has other reasons that make them unsuitable for participating in this clinical study.

Where this trial is running

Shanghai

• Shanghai East Hospital — Shanghai, China (Recruiting)

Study contacts

• Study coordinator: lily Liu, MD

Conditions Non Small Cell Lung Cancer; WSD0922; WSD0922-FU; NSCLC; CNS metastasis; Brain metastasis; EGFR; C797S