A Phase I/II Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of WJ13405 Monotherapy in Patients With Advanced or Mentastatic Non-Small Cell Lung Cancer
Overview
- Phase
- Phase 1
- Intervention
- WJ13404 tablets
- Conditions
- Locally Advanced or Metastatic NSCLC
- Sponsor
- Suzhou Junjing BioSciences Co., Ltd.
- Enrollment
- 14
- Locations
- 1
- Primary Endpoint
- DLT
- Status
- Terminated
- Last Updated
- 7 months ago
Overview
Brief Summary
This is an open-label phase I/II preliminary study, including dose escalation, dose expansion, and efficacy expansion, to evaluate drug safety, tolerability, PK, and efficacy. The dose escalation study evaluates the IMP's safety, tolerability, and PK in patients with locally advanced or metastatic NSCLC who have experienced disease progression after third-generation EGFR-TKI therapy. The dose expansion study, after 2-3 dose levels are selected based on dose escalation results, further investigates the IMP's safety, tolerability, and PK, explores preliminary efficacy, and determines RP2D in patients with locally advanced or metastatic NSCLC harboring EGFR C797X mutation. The efficacy expansion study evaluates the IMP's safety and efficacy in patients with locally advanced or metastatic NSCLC harboring EGFR C797X mutation.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Aged ≥ 18 years old, male or female;
- •Histologically or cytologically confirmed locally advanced or recurrent/metastatic advanced NSCLC that is inoperable, is subject to progression or intolerability after the standard of care, or is unable to be treated or has not been treated by the standard of care;
- •Dose escalation: patients with EGFR sensitive mutation who have experienced disease progression after third-generation EGFR-TKI therapy;
- •Dose expansion and efficacy expansion: patients with proven EGFR C797X mutation;
- •Patients who agree to provide tumor tissues and blood samples for EGFR mutation analysis (certain patients who are unable to provide qualified tumor tissues may be enrolled once approved by investigators and the Sponsor);
- •At least one measurable lesion as per RECIST v1.1;
- •ECOG PS score of 0-1;
- •Expected survival of more than 12 weeks;
- •Sufficient vital organ functions at screening (requiring no blood transfusion, use of hematopoietic stimulating factor, or use of human albumin preparation within 14 days before screening):
- •ANC ≥ 1.5 × 109/L;
Exclusion Criteria
- •Patients who have received systemic anti-tumor therapy within 4 weeks before the first dose, including chemotherapy, targeted therapy, anti-vascular drug therapy, biologic therapy, immunotherapy, radiotherapy, or other IMP therapy; moreover, patients who have received EGFR-TKI targeted therapy may be enrolled if 5 half-lives have passed after discontinuation;
- •Patients who are receiving strong CYP3A inhibitors or inducers; or those who have yet to reach 5 half-lives after discontinuation of a strong inhibitor, or 5 half-lives or 14 days (whichever is longer) after discontinuation of a strong inducer at the time of the first WJ13404 dosing;
- •Patients who have experienced adverse events caused by previous anti-tumor therapy that have yet to improve to CTCAE v5.0 grade ≤ 1 at screening (except for neurotoxicity and alopecia, which cannot be recovered as assessed by investigators);
- •Patients who are plagued by other malignancies (except for non-melanoma basal or squamous cell carcinoma of the skin, carcinoma in situ of the breast/cervix, superficial bladder cancer, thyroid cancer, and other carcinomas in situ, treated with curative intent and without evidence of recurrent disease) concurrently or within 5 years before treatment initiation;
- •History of diseases causing chronic diarrhea, including but not limited to Crohn's disease and irritable bowel syndrome;
- •Active gastrointestinal disease or other conditions that may significantly compromise drug absorption, metabolism, or excretion;
- •Patients known to have undergone organ transplantation or stem cell transplantation; patients who have undergone major surgery or serious trauma within 4 weeks before the first dose (excluding needle biopsy for sample collection);
- •Patients who are suffering from carcinomatous meningitis and spinal cord compression;
- •Patients who meet one of the following cardiac criteria: Unexplained or cardiovascular-caused presyncope or syncope, ventricular tachycardia, ventricular fibrillation, or cardiac arrest, with average corrected QT interval (based on 3 ECGs taken at rest, QTc, using the Fridericia's correction formula) \> 450 ms in males or \> 470 ms in females. Various clinically significant cardiac rhythm, conduction, or resting ECG morphological abnormalities, such as complete left bundle branch block, third-degree conduction block, second-degree conduction block, PR interval \> 250 ms, and echocardiography-suggested left ventricular ejection fraction (LVEF) \< 50%. Various factors that may increase the risks of QTc prolongation or arrhythmic events, such as heart failure, hypokalemia, congenital long QT syndrome, history of immediate family members with long QT syndrome or sudden death of unknown cause before age 40, and current receipt of any drug known to prolong the QT interval;
- •Unstable systemic diseases, such as active infection requiring systemic drug therapy, poorly controlled hypertension, unstable angina, congestive heart failure, serious hepatic, renal, or metabolic conditions including cirrhosis, renal failure, and uremia;
Arms & Interventions
Experimental:WJ13404 tablets
Dose escalation: 6 dose levels The dose escalation study is proposed to include 6 dose levels: 30, 90, 180, 270, 360, and 480 mg once daily. (It can be adjusted based on clinical PK data and safety results after discussion between PI and the sponsor). Dose-expansion: After the initial data evaluation, the Sponsor and the SMC will select 2-3 dose levels to evaluate drug safety and PK further, explore its preliminary efficacy, and determine RP2D. Efficacy expansion: The RP2D determined in dose escalation and dose expansion will be applied.
Intervention: WJ13404 tablets
Outcomes
Primary Outcomes
DLT
Time Frame: up to 2 years (only for dose escalation and dose expansion）
DLT is defined as any of the following toxicities that occur during the DLT observation and are deemed by investigators possibly, probably, or definitely related to WJ13404 as per NCI-CTCAE v5.0
adverse events（AE) and serious adverse events（SAE)
Time Frame: up to 3 years
To evaluate incidence，severity and outcome of adverse events（AE),and serious adverse events（SAE)
ORR
Time Frame: up to 3 years
Proportion of patients who have the best response of confirmed or partial response as per RECIST v1.1.ORR, along with its 95% CI, will be calculated
Secondary Outcomes
- CL/F(up to 3 years)
- Cmax(up to 3 years)
- Tmax(up to 3 years)
- Vss(up to 3 years)
- AR(up to 3 years)
- Css-min(up to 3 years)
- adverse events（AE) and serious adverse events（SAE)(up to 1 years（only for efficacy expansion stage）)
- DOR(up to 3 years)
- Css-ave(up to 3 years)
- ORR(up to 3 years)
- PFS(up to 3 years)
- OS(up to 3 years)
- AUC 0-t(up to 3 years)
- Vd/F(up to 3 years)
- t1/2(up to 3 years)
- λz(up to 3 years)
- Css-max(up to 3 years)
- AUCtau-ss(up to 3 years)
- DF(up to 3 years)
- DCR(up to 3 years)