A Phase I/II, Dose-Escalation, Dose-Expansion, and Efficacy-Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of WJ22096 Tablets Administered Orally in Patients With Advanced Solid Tumors
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).
• 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):
‣ Absolute neutrophil count (ANC) ≥ 1.5 x 10⁹/L
⁃ Platelets (PLT) ≥ 100 x 10⁹/L
⁃ Hemoglobin (Hb) \> 90 g/L
⁃ Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 3.0 × upper limit of normal (ULN) (or ≤ 5 × ULN if liver metastases are present);
⁃ Total bilirubin ≤1.5 × ULN;
⁃ Serum creatinine ≤ 1.5 × ULN or creatinine clearance (Ccr, calculated using the Cockcroft-Gault formula) ≥ 45 mL/min;
• 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.
• 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).