A Study to Assess the Efficacy and Safety of WSD0922-FU in Patients with EGFRm+ Advanced Non-small Cell Lung Cancer

Phase 1

Recruiting

• Conditions: EGFR Mutation Positive Advanced Non-Small Cell Lung Cancer
• Interventions: Drug: WSD0922-FU

• Registration Number: NCT06631989
• Lead Sponsor: Wayshine Biopharm, Inc.

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.

Study Timeline

• Study Start: 2024-08-21
• Study First Submitted: 2024-08-25
• Status Verified: 2024-10
• Study First Submitted QC: 2024-10-05
• Last Update Submitted: 2024-10-05
• Study First Posted: 2024-10-08
• Last Update Posted: 2024-10-08
• Primary Completion: 2026-06-30
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 100

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Dose escalation (WSD0922-FU)	WSD0922-FU	Patients receive WSD0922-FU PO QD on C0D1 to C0D3, then BID on C1D1 to C1D21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, MRI, and blood sample collection on study.
Dose expansion (WSD0922-FU)	WSD0922-FU	Patients receive WSD0922-FU PO BID on C1D1 to C1D21 using dosage selected from Dose escalation. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, MRI, and blood sample collection on study.
Dose extension (WSD0922-FU)	WSD0922-FU	Patients receive WSD0922-FU PO BID on C1D1 to C1D21 using RP2D. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT, MRI, and blood sample collection on study.

Primary Outcome Measures

Name	Time	Method
PartB: To evaluate the efficacy of WSD0922-FU in the treatment of advanced non-small cell lung cancer patients	8 months	Overall Response Rate (ORR) assessed by an Imaging review board (IRC)
PartA: To evaluate the safety of WSD0922-FU in patients with NSCLC	8 months	Safety (incidence and severity of adverse events \[AE\])
PartA: To evaluate the tolerability of WSD0922-FU in patients with NSCLC	8 months	Incidence and quantity of dose-limiting toxicity (DLT)
PartA: To evaluate the Maximum Tolerated Dose (MTD) of WSD0922-FU in patients with NSCLC	8 months	Incidence of Dose-Limiting Toxicities (DLTs)
PartA: Recommended Phase II Dose (RP2D) of WSD0922-FU in patients with NSCLC	8 months	Recommended Phase II Dose (RP2D)

Secondary Outcome Measures

Name	Time	Method
PartA (dose escalation and expansion): PK exposure parameter: Maximum Plasma Concentration (Cmax)	12 months	Maximum Plasma Concentration (Cmax)
PartA (dose escalation and expansion): PK exposure parameter: Time To Maximum Plasma Concentration (Tmax)	12 months	Time To Maximum Plasma Concentration (Tmax)
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)	12 months	Area Under The Plasma Concentration-Time Curve From Time Zero To Time With Last Measurable Concentration (AUC0-t)
PartA (dose escalation and expansion): PK exposure parameter: Area Under The Plasma Concentration-Time Curve From Time Zero To Infinity (AUC0-∞)	12 months	Area Under The Plasma Concentration-Time Curve From Time Zero To Infinity (AUC0-∞)
PartA (dose escalation and expansion): PK exposure parameter: Terminal Elimination Half-Life (t½)	12 months	Terminal Elimination Half-Life (t½)
PartA (dose escalation and expansion): PK exposure parameter: Apparent Terminal Elimination Rate Constant (λz)	12 months	Apparent Terminal Elimination Rate Constant (λz)
PartA (dose escalation and expansion): PK exposure parameter: Apparent Clearance (CL)	12 months	Apparent Clearance (CL)
PartA (dose escalation and expansion): PK exposure parameter: Apparent volume of distribution (Vd)	12 months	Apparent volume of distribution (Vd)
PartA (dose escalation and expansion): PK exposure parameter: Mean Residence Time (MRT)	12 months	Mean Residence Time (MRT)
PartA (dose escalation and expansion): Steady state pharmacokinetic parameter: Area Under the Steady-State Concentration-Time Curve（AUCss）	12 months	Area Under the Steady-State Concentration-Time Curve（AUCss）
PartA (dose escalation and expansion): Steady state pharmacokinetic parameter: Area Under the Steady-State Concentration-Time Curve from 0 to Infinity（AUC0-∞,ss）	12 months	Area Under the Steady-State Concentration-Time Curve from 0 to Infinity（AUC0-∞,ss）
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）	12 months	Area Under the Steady-State Concentration-Time Curve from 0 to Time t （AUC0-t,ss）
PartA (dose escalation and expansion): Steady state pharmacokinetic parameter: Average Steady-State Concentration（Cav）	12 months	Average Steady-State Concentration（Cav）
PartA (dose escalation and expansion): Steady state pharmacokinetic parameter: Steady-State Clearance（CLss）	12 months	Steady-State Clearance（CLss）
PartA (dose escalation and expansion): Maximum Steady-State Concentration（Cmax,ss）	12 months	Maximum Steady-State Concentration（Cmax,ss）
PartA (dose escalation and expansion): Minimum Steady-State Concentration（Cmin,ss）	12 months	Minimum Steady-State Concentration（Cmin,ss）
PartA (dose escalation and expansion): Trough Concentration（Ctrough）	12 months	Trough Concentration（Ctrough）
PartA (dose escalation and expansion): Accumulation Ratio（Ra）	12 months	Accumulation Ratio（Ra）
PartA (dose escalation and expansion): Time to Maximum Concentration at Steady State（Tmax,ss）	12 months	Time to Maximum Concentration at Steady State（Tmax,ss）
PartA (dose escalation and expansion): Fluctuation Degree（DF）	12 months	Fluctuation Degree（DF）
PartA (dose escalation and expansion): Volume of Distribution Calculated from the Terminal Elimination Phase（Vz）	12 months	Volume of Distribution Calculated from the Terminal Elimination Phase（Vz）
PartB (dose extension): 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)
PartB (dose extension): To evaluate the initial efficacy of WSD0922-FU in patients with advanced non-small cell lung cancer: ORR	12 months	ORR assessed by the investigator
PartB (dose extension): To evaluate the initial efficacy of WSD0922-FU in patients with advanced non-small cell lung cancer: DCR	12 months	DCR assessed by investigator and IRC
PartB (dose extension): To evaluate the initial efficacy of WSD0922-FU in patients with advanced non-small cell lung cancer: DOR	12 months	DOR assessed by investigator and IRC
PartB (dose extension): To evaluate the initial efficacy of WSD0922-FU in patients with advanced non-small cell lung cancer: PFS	12 months	PFS assessed by investigator and IRC
PartB (dose extension): To evaluate the initial efficacy of WSD0922-FU in patients with advanced non-small cell lung cancer: OS	12 months	Overall survival (OS)
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	12 months	6-month Overall survival (OS) rate
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	12 months	12-month Overall survival (OS) rate
PartB (dose extension): To evaluate the initial efficacy of WSD0922-FU in patients with advanced non-small cell lung cancer: Intracranial ORR	12 months	Intracranial ORR was assessed by investigators according to RANO-BM criteria
PartA: PK characteristics of WSD0922 in patients with non-small cell lung cancer based on population PK analysis method	12 months	The PK characteristics ( Maximum Plasma Concentration \[Cmax\]) of WSD0922 in patients with non-small cell lung cancer were characterized based on population PK analysis method
PartB: PK characteristics of WSD0922 in patients with non-small cell lung cancer based on population PK analysis method	12 months	The PK characteristics ( Maximum Plasma Concentration \[Cmax\]) of WSD0922 in patients with non-small cell lung cancer were characterized based on population PK analysis method
PartA: To evaluate the effect of WSD0922-FU on reported outcomes (PRO) in patients with non-small cell lung cancer.	12 months	Participants' overall health was assessed using the EORTC Quality of Life questionnaires QLQ-C30.
PartA - To evaluate the effect of WSD0922-FU on reported outcomes (PRO) in patients with non-small cell lung cancer.	12 months	Participants' overall health was assessed using the EORTC Quality of Life questionnaires QLQ-LC13.
PartB: To evaluate the effect of WSD0922-FU on reported outcomes (PRO) in patients with non-small cell lung cancer.	12 months	Participants' overall health was assessed using the EORTC Quality of Life questionnaires QLQ-C30.
PartB - To evaluate the effect of WSD0922-FU on reported outcomes (PRO) in patients with non-small cell lung cancer.	12 months	Participants' overall health was assessed using the EORTC Quality of Life questionnaires QLQ-LC13.

Trial Locations

Locations (1)

Shanghai East Hospital; 🇨🇳 Shanghai, Shanghai, China