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This is a Phase I/II, open-label, preliminary study of safety, tolerability, pharmacokinetics, and efficacy. The study comprises three parts: a Dose Escalation cohort, a Dose Expansion cohort, and an Efficacy Expansion cohort.
Dose Escalation cohort aims to evaluate the safety, tolerability, pharmacokinetic (PK) characteristics, and preliminary efficacy of WJ22096 Tablets in patients with advanced solid tumors for whom standard therapies have failed, are not tolerated, or for whom no standard therapy exists.
Dose Expansion cohort Based on an evaluation of preliminary data, the Sponsor and the Safety Monitoring Committee (SMC) will select 1-2 dose levels to further evaluate preliminary efficacy, safety, tolerability, and PK characteristics, and to confirm the Recommended Phase 2 Dose (RP2D). Each dose cohort will enroll approximately 9-12 subjects with advanced solid tumors (for whom standard therapies have failed, are not tolerated, or for whom no standard therapy exists), predominantly comprising patients with Non-Small Cell Lung Cancer (NSCLC), Colorectal Cancer (CRC), and Pancreatic Cancer.
Efficacy Expansion cohort aims to evaluate the efficacy, safety, tolerability, and PK characteristics at the selected dose in patients with specific tumor types, such as NSCLC, CRC, and Pancreatic Cancer. The dosing regimen will be the RP2D determined during the Dose Escalation and Dose Expansion cohorts. It is initially planned to expand 2-3 cohorts using Simon's two-stage minimax design, with approximately 20-40 subjects planned for enrollment in each cohort. (The specific tumor types for expansion, sample size, and number of cohorts will be adjusted by the Principal Investigator (PI) and the Sponsor based on results from the preceding stages of the trial).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Experimental:WJ22096 tablets | Experimental | WJ22096 orally once daily after meal |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| WJ22096 | Drug | WJ22096: orally once daily after meal |
|
| Measure | Description | Time Frame |
|---|---|---|
| DLT (Dose Limiting Toxicity) | It is suitable for dose escalation .DLT is defined as any of AE that Safety Monitoring Committee considers to have occurred during the DLT observation period and may be causally related to WJ22096 and meet DLTcriteria. | up to 3 years |
| Adverse Events (AE) / Serious Adverse Events (SAE) | Incidence and severity of adverse events (AE) and serious adverse events (SAE) as assessed according to NCI-CTCAE 5.0, as well as abnormalities in physical examination, ECOG score, vital signs, electrocardiogram, ophthalmic tests and laboratory tests. | up to 3 years |
| MTD (Maximal Tolerable Dose) | Defined as the dose level at which the estimated toxicity probability is closest to the target toxicity probability during the DLT observation period | up to 3 years |
| RP2D (Recommended Phase 2 Dose) | RP2D will be determined based on a combination of safety, tolerability, PK and/or pharmacodynamic studies . | up to 3 years |
| ORR (Objective Response Rate) (efficacy expansion cohort) | It is suitable for the curative effect development stage.Objective Response Rate by RECIST 1.1. | up to 3 years |
| Measure | Description | Time Frame |
|---|---|---|
| Cmax | Maximum Plasma Concentration | up to 3 years |
| Tmax | Time to Cmax | up to 3 years |
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Inclusion Criteria:
Voluntary participation in this study, with a signed informed consent form (ICF) provided after being fully informed;
Age ≥ 18 years, regardless of sex;
Histologically and/or cytologically confirmed diagnosis of advanced solid tumors, who have failed standard therapy, are intolerant to standard therapy, or for whom no standard therapy is available;
Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1;
Estimated life expectancy > 12 weeks;
Adequate hematological and organ function, with the following laboratory results obtained within 7 days prior to the first administration of the study drug (no blood transfusions, hematopoietic stimulating factors, or human albumin preparations within 14 days prior to the test):
All acute toxicities from prior anti-tumor therapies or surgical procedures must have resolved to baseline severity or to ≤ Grade 1 according to NCI CTCAE v5.0 (exceptions include alopecia or pigmentation);
Female subjects of childbearing potential (WOCBP) must have a negative serum pregnancy test within 7 days prior to the first dose and agree to use effective contraceptive measures during the study drug administration period and for 3 months after the last dose. Male subjects whose sexual partners are WOCBP must agree to use effective contraceptive measures during the study drug administration period and for 3 months after the last dose.
Specific Inclusion Criteria:
At least one measurable tumor lesion as defined by RECIST v1.1, with no biopsy of the target lesion within the prior 2 weeks (Applicable to dose expansion and efficacy expansion cohorts);
The Non-Small Cell Lung Cancer (NSCLC) cohort will prioritize the enrollment of subjects with G12C mutations (Applicable to the efficacy expansion cohort);
Subjects with pancreatic cancer must have received ≤2 prior lines of therapy (Applicable to dose expansion and efficacy expansion cohort).
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Tong FANG | Contact | 862153391528 | clinicaltrial@jingaobio.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Peking Union Medical College Hospital | Recruiting | Beijing | Beijing Municipality | 100730 | China |
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| AUC0-t | Area under the concentration versus time curve from time 0 to the last measurable concentration | up to 3 years |
| AUC0-inf | AUC from time 0 to infinity | up to 3 years |
| t1/2 | Elimination half life time | up to 3 years |
| CL/F | Apparent Clearance | up to 3 years |
| Vd/F | Apparent volume of distribution | up to 3 years |
| RAC | Accumulation index | up to 3 years |
| FD | degree of fluctuation | up to 3 years |
| DOR | Duration of response | up to 3 years |
| DCR | Disease Control Rate | up to 3 years |
| PFS | Progression-free survival | up to 3 years |
| OS | Overall survival | up to 3 years |
| ORR (dose escalation and dose expansion stage) | It is suitable for the curative effect development stage.Objective Response Rate by RECIST 1.1. | up to 3 years |
| adverse events (AE) and serious adverse events (SAE) (efficacy expansion stage) | To evaluate incidence, severity and outcome of adverse events (AE),and serious adverse events (SAE) | up to 3 years |