Clinical trial NCT06631989: A Study to Assess the Efficacy and Safety of WSD0922-FU in Patients with EGFRm+ Advanced Non-small Cell Lung Cancer
Official title: A Phase I/II Multicenter, Open Label, Single-arm Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of WSD0922-FU in the Treatment of Advanced Non-small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: EGFR Mutation Positive Advanced Non-Small Cell Lung Cancer
Keywords: NSCLC
EGFR
C797S
BM
Lead sponsor: Wayshine Biopharm, Inc.
Sponsor class: INDUSTRY
First posted: 2024-10-08
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Part A (Dose escalation and expansion study) ; Part B (single-arm extension study).
Primary purpose: TREATMENT

Brief summary: This study is a multicenter, open label, single-arm phase I/II clinical study of WSD0922-FU conducted in China, including Part A (dose escalation and expansion study) and Part B (dose extension). To explore the safety, tolerability, pharmacokinetic characteristics and efficacy of WSD0922-FU in patients with non-small cell lung cancer (NSCLC) with C797S mutation after first-line third-generation EGFR-TKI resistance (Osimertinib, Almonertinib, Furmonertinib, Befotertinib).

Detailed description: A multicenter, open label, single-arm phase I/II clinical study of WSD0922-FU conducted in China.

To explore the safety, tolerability, pharmacokinetic characteristics and efficacy of WSD0922-FU in patients with non-small cell lung cancer (NSCLC) with C797S mutation after first-line third-generation EGFR-TKI resistance.

Eligibility criteria: Inclusion Criteria:

1. Age 18-75 years old (including the threshold value), gender is not limited;
2. Locally advanced or metastatic NSCLC confirmed by pathology;
3. Patients who have been genetically tested to carry EGFR C797S sensitive mutations (including deletion mutations in exon 19 and L858R point mutations in exon 21) and have disease progression during or after previous first-line therapy with third-generation EGFR-TKI (Osimertinib, Almonertinib, Furmonertinib, Befotertinib) inhibitors;
4. Blood samples must be provided for testing and must be taken during or after disease progression following the last EGFR TKI inhibitor treatment; Test results from the last treatment of previous EGFR TKI inhibitors (not limited to blood samples) are acceptable;
5. Must have a minimum life expectancy of \>= 3 months;
6. 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.
7. Physical Status (ECOG PS) score of the Eastern United States Tumor Collaboration Group was 0-1;
8. Have full organ function:

   1. Blood system (has not received blood transfusion or hematopoietic stimulating factor treatment within 14 days prior to the first dose) :

      * Absolute neutrophil count (ANC) ≥1.5×10\^9/L;
      * Platelet (PLT) count ≥100×10\^9/L;
      * Hemoglobin (HB) ≥90g/L;
   2. Liver function:

      * Total bilirubin (TBIL) ≤1.5× upper limit of normal (ULN);
      * Alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≤3×ULN (AST and ALT≤5×ULN in patients with liver metastasis);
   3. Kidney function:

      * Serum creatinine (Cr) ≤1.5×ULN or creatinine clearance (Ccr) ≥60ml/min/1.73m2 (Cockcroft-Gault formula, creatinine \>1.5×ULN only);
   4. Coagulation function:

      * Activated partial thromboplastin time (APTT) ≤1.5×ULN;
      * International Standardized ratio (INR) ≤1.5×ULN;
9. Eligible patients (male and female) who are fertile must agree to use a reliable contraceptive method (hormonal or barrier method or abstinence) with their partner during the trial period and for at least 90 days after the last dose; Blood pregnancy tests (β-HCG) must be negative for female subjects of reproductive age within 7 days prior to the first use of the study drug;
10. Subjects are required to give informed consent to this study before the experiment and sign a written informed consent voluntarily.

Exclusion Criteria:

1. 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, except for the following:

   1. Oral fluoropyrimidine class and small molecule targeted drugs are within 2 weeks before the first use of the study drug or within 5 half-lives of the drug (whichever is shorter);
   2. Chinese medicine with anti-tumor indications is within 2 weeks before the first use of the study drug;
2. Have previously received more than one EGFR-TKI inhibitor;
3. Received other unlisted clinical study drugs or treatments within 4 weeks before the first administration;
4. 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;
5. Used strong CYP3A4 inhibitors or strong CYP3A4 inducers within 7 days before the first use of the study drug;
6. Known to carry any other known driver gene mutations (including but not limited to T790M, EGFR exon 20 insertion, KRAS, BRAF V600E, NTRK1/2/3, HER2, ALK, ROS1, MET, or RET);
7. Known active brain metastasis or progression evidence. Active brain metastasis refers to malignant central nervous system (CNS) metastasis diagnosed by enhanced MRI/CT, excluding brain abscesses, cerebrovascular diseases, and other diseases, and showing new neurological abnormalities such as headache, vomiting, vision impairment, mental abnormalities, language disorders, unilateral limb sensory abnormalities or weakness, olfactory hallucinations, hemiplegia, or staggering gait, tinnitus, or deafness. Within 14 days before the first administration of the study drug, palliative radiotherapy or radiosurgery for brain metastases, or the need for more than 10 mg/day of prednisone or equivalent glucocorticoids. Subjects with treated, stable brain metastases or untreated asymptomatic brain metastases are allowed to enroll;
8. Known intracranial hemorrhage and/or bleeding diathesis;
9. Other primary malignant tumors within 2 years before the first administration of the study drug. Limited cured tumors such as basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, prostatic intraepithelial cancer, cervical intraepithelial cancer, and breast intraepithelial cancer are excluded;
10. 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);
11. Skin/pressure ulcers, chronic leg ulcers, known active gastric ulcers, or non-healing wounds;
12. History of severe allergies, or allergies to any active or inactive ingredients of the study drug;
13. Severe infections requiring intravenous antibiotic infusion or hospitalization at the time of screening; or uncontrollable active infections within 4 weeks before administration;
14. Known active or suspected autoimmune diseases; or known active ocular diseases (such as active wet age-related macular degeneration, diabetic retinopathy with macular edema);
15. Human immunodeficiency virus (HIV) (HIV1/2 antibody) positive, syphilis spirochete antibody positive (those who are syphilis spirochete antibody positive need to undergo a confirmatory test, and those who are negative in the confirmatory test can be included), active hepatitis B (HBsAg positive and HBV-DNA\>1000 IU or research center detection limit \[only when the research center detection limit is higher than 1000 IU/mL\]); active hepatitis C (HCV antibody positive but HCV-RNA \< research center detection limit patients are allowed to be included);
16. Patients with interstitial lung disease;
17. History of severe cardiovascular diseases, including but not limited to:

    1. Severe cardiac rhythm or conduction abnormalities, such as clinically interventional ventricular arrhythmias, second to third-degree atrioventricular block; corrected QTcF interval for males \>450 milliseconds, for females \>470 milliseconds;
    2. Acute coronary syndrome, congestive heart failure, aortic dissection, stroke, or other grade 3 or above cardiovascular and cerebrovascular events within 6 months before the first administration;
    3. American New York Heart Association (NYHA) heart function classification ≥II or left ventricular ejection fraction (LVEF) ≤50%;
    4. Clinically uncontrollable hypertension (specifically systolic blood pressure ≥150mmHg and/or diastolic blood pressure ≥100mmHg);
18. Unable to orally swallow medication, or there is a condition that significantly affects gastrointestinal absorption as judged by the researcher;
19. 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), pericardial effusion (excluding a small amount of pericardial effusion that has been stable for more than 2 weeks);
20. Known alcohol or drug dependence;
21. Mental disorders or poor compliance;
22. Pregnant or lactating women;
23. The investigator believes that the subject has other reasons that make them unsuitable for participating in this clinical study.

Primary outcomes:
measure: PartB: To evaluate the efficacy of WSD0922-FU in the treatment of advanced non-small cell lung cancer patients
timeFrame: 8 months
measure: PartA: To evaluate the safety of WSD0922-FU in patients with NSCLC
timeFrame: 8 months
measure: PartA: To evaluate the tolerability of WSD0922-FU in patients with NSCLC
timeFrame: 8 months
measure: PartA: To evaluate the Maximum Tolerated Dose (MTD) of WSD0922-FU in patients with NSCLC
timeFrame: 8 months
measure: PartA: Recommended Phase II Dose (RP2D) of WSD0922-FU in patients with NSCLC
timeFrame: 8 months
Secondary outcomes:
measure: PartA (dose escalation and expansion): PK exposure parameter: Maximum Plasma Concentration (Cmax)
timeFrame: 12 months
measure: PartA (dose escalation and expansion): PK exposure parameter: Time To Maximum Plasma Concentration (Tmax)
timeFrame: 12 months
measure: PartA (dose escalation and expansion): PK exposure parameter: Area Under The Plasma Concentration-Time Curve From Time Zero To Time With Last Measurable Concentration (AUC0-t)
timeFrame: 12 months
measure: PartA (dose escalation and expansion): PK exposure parameter: Area Under The Plasma Concentration-Time Curve From Time Zero To Infinity (AUC0-∞)
timeFrame: 12 months
measure: PartA (dose escalation and expansion): PK exposure parameter: Terminal Elimination Half-Life (t½)
timeFrame: 12 months
measure: PartA (dose escalation and expansion): PK exposure parameter: Apparent Terminal Elimination Rate Constant (λz)
timeFrame: 12 months
measure: PartA (dose escalation and expansion): PK exposure parameter: Apparent Clearance (CL)
timeFrame: 12 months
measure: PartA (dose escalation and expansion): PK exposure parameter: Apparent volume of distribution (Vd)
timeFrame: 12 months
measure: PartA (dose escalation and expansion): PK exposure parameter: Mean Residence Time (MRT)
timeFrame: 12 months
measure: PartA (dose escalation and expansion): Steady state pharmacokinetic parameter: Area Under the Steady-State Concentration-Time Curve（AUCss）
timeFrame: 12 months
measure: PartA (dose escalation and expansion): Steady state pharmacokinetic parameter: Area Under the Steady-State Concentration-Time Curve from 0 to Infinity（AUC0-∞,ss）
timeFrame: 12 months
measure: PartA (dose escalation and expansion): Steady state pharmacokinetic parameter: Area Under the Steady-State Concentration-Time Curve from 0 to Time t （AUC0-t,ss）
timeFrame: 12 months
measure: PartA (dose escalation and expansion): Steady state pharmacokinetic parameter: Average Steady-State Concentration（Cav）
timeFrame: 12 months
measure: PartA (dose escalation and expansion): Steady state pharmacokinetic parameter: Steady-State Clearance（CLss）
timeFrame: 12 months
measure: PartA (dose escalation and expansion): Maximum Steady-State Concentration（Cmax,ss）
timeFrame: 12 months
measure: PartA (dose escalation and expansion): Minimum Steady-State Concentration（Cmin,ss）
timeFrame: 12 months
measure: PartA (dose escalation and expansion): Trough Concentration（Ctrough）
timeFrame: 12 months
measure: PartA (dose escalation and expansion): Fluctuation Degree（DF）
timeFrame: 12 months
measure: PartA (dose escalation and expansion): Accumulation Ratio（Ra）
timeFrame: 12 months
measure: PartA (dose escalation and expansion): Time to Maximum Concentration at Steady State（Tmax,ss）
timeFrame: 12 months
measure: PartA (dose escalation and expansion): Volume of Distribution Calculated from the Terminal Elimination Phase（Vz）
timeFrame: 12 months
measure: PartB (dose extension): To evaluate the safety of WSD0922-FU in patients with advanced non-small cell lung cancer
timeFrame: 12 months
measure: PartB (dose extension): To evaluate the initial efficacy of WSD0922-FU in patients with advanced non-small cell lung cancer: ORR
timeFrame: 12 months
measure: PartB (dose extension): To evaluate the initial efficacy of WSD0922-FU in patients with advanced non-small cell lung cancer: DCR
timeFrame: 12 months
measure: PartB (dose extension): To evaluate the initial efficacy of WSD0922-FU in patients with advanced non-small cell lung cancer: DOR
timeFrame: 12 months
measure: PartB (dose extension): To evaluate the initial efficacy of WSD0922-FU in patients with advanced non-small cell lung cancer: PFS
timeFrame: 12 months
measure: PartB (dose extension): To evaluate the initial efficacy of WSD0922-FU in patients with advanced non-small cell lung cancer: OS
timeFrame: 12 months
measure: PartB (dose extension): To evaluate the initial efficacy of WSD0922-FU in patients with advanced non-small cell lung cancer: 6-month Overall survival (OS) rate
timeFrame: 12 months
measure: PartB (dose extension): To evaluate the initial efficacy of WSD0922-FU in patients with advanced non-small cell lung cancer: 12-month Overall survival (OS) rate
timeFrame: 12 months
measure: PartB (dose extension): To evaluate the initial efficacy of WSD0922-FU in patients with advanced non-small cell lung cancer: Intracranial ORR
timeFrame: 12 months
measure: PartA: PK characteristics of WSD0922 in patients with non-small cell lung cancer based on population PK analysis method
timeFrame: 12 months
measure: PartB: PK characteristics of WSD0922 in patients with non-small cell lung cancer based on population PK analysis method
timeFrame: 12 months
measure: PartA: To evaluate the effect of WSD0922-FU on reported outcomes (PRO) in patients with non-small cell lung cancer.
timeFrame: 12 months
measure: PartA - To evaluate the effect of WSD0922-FU on reported outcomes (PRO) in patients with non-small cell lung cancer.
timeFrame: 12 months
measure: PartB: To evaluate the effect of WSD0922-FU on reported outcomes (PRO) in patients with non-small cell lung cancer.
timeFrame: 12 months
measure: PartB - To evaluate the effect of WSD0922-FU on reported outcomes (PRO) in patients with non-small cell lung cancer.
timeFrame: 12 months
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai East Hospital
state: Shanghai
Study officials:
affiliation: Shanghai East Hospital
name: Caicun Zhou, MD
role: PRINCIPAL_INVESTIGATOR
References: