Non Small Cell Lung Cancer (NSCLC)
Conditions
Keywords
WSD0922, WSD0922-FU, NSCLC, CNS metastasis, Brain metastasis, EGFR, C797S, Del19, L858R
Brief summary
This is a Phase I/II, Open Label Study of WSD0922-FU in Combination with Osimertinib for Patients with Locally Advanced or Metastatic Non-Small Cell Lung Cancer whose disease has progressed with third-generation EGFR-TKI with C797S mutation or is newly diagnosed with CNS metastasis with EGFR Del19 or L858R mutation
Detailed description
WSD0922-FU is a potent reversible inhibitor of both the single EGFRm+ and dual EGFRm+/C797S+ receptor forms of EGFR with selectivity margin over wild-type EGFR. This study aims to explore the safety, tolerability, pharmacokinetic characteristics and efficacy of WSD0922-FU combined with Osimertinib in patients with non-small cell lung cancer (NSCLC) with C797S mutation after first-line third-generation EGFR-TKI resistance, and then further confirm the safety and efficacy for newly diagnosed NSCLC BM patients with classical EGFR Del19 or L858R mutation
Interventions
Drug: Osimertinib Procedure: Biospecimen Collection - blood samples Undergo collection of blood samples Procedure: Computed Tomography and/or Magnetic Resonance Imaging Undergo CT and/or MRI Drug: Osimertinib Given PO, 80mg, once daily
DRUGWSD0922-FU
Drug: WSD0922-FU Procedure: Biospecimen Collection - blood samples Undergo collection of blood samples Procedure: Computed Tomography and/or Magnetic Resonance Imaging Undergo CT and/or MRI Drug: WSD0922-FU Given PO
Sponsors
Wayshine Biopharm, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Part A (Dose escalation study) ; Part B (Does expansion study).
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PartA: To evaluate the safety of WSD0922-FU combined with Osimertinib in patients with NSCLC | 12 months | Safety (incidence and severity of adverse events \[AE\]) |
| PartB: To evaluate the efficacy of WSD0922-FU combined with Osimertinib in patients with NSCLC | every 6 weeks, up to 2 years | ORR |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response (DoR) | every 6 weeks, up to 24 months | proportion of patients with the time from the date of first documented response until the date of documented progression or death in the absence of disease progression |
| PFS | every 6 weeks, up to 24 months | proportion of patients with the time from randomization until the date of objective disease progression or death |
| To evaluate the safety of WSD0922-FU in patients with advanced non-small cell lung cancer | 12 months | Treatment-Emergent Adverse Events (TEAEs), Treatment-Related Adverse Events (TRAEs) |
| Intracranial Duration of Response (iDoR) | every 6 weeks, up to 24 months | proportion of patients with the time from the date of first documented response until the date of documented progression or death in the absence of disease progression per RANO BM |
| iPFS | every 6 weeks, up to 24 months | proportion of patients with the time from randomization until the date of objective disease progression or death per RANO BM |
| Intracranial Disease Control Rate (iDCR) | every 6 weeks, up to24 months | the percentage of patients who have a best overall response of CR or PR or SD per RANO BM |
| Disease Control Rate (DCR) | every 6 weeks, up to 24 months | the percentage of patients who have a best overall response of CR or PR or SD |
Countries
China
Contacts
Primary Contactlily Liu, MD
Backup ContactWei Zhong, PhD
Outcome results
None listed