NSCLC
Conditions
Interventions
Ib increasing phase:PLB1004 Capsules in Combination with Doublet Chemotherapy
Ib progressive phase:PLB1004 Capsules in Combination with Doublet Chemotherapy
Phase II stage:PLB1004 Capsules in Combination with Doublet Chemotherapy
Sponsors
Shanghai Chest Hospital
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Male or female subjects aged =18 years at the time of signing the informed consent form (ICF). 2. - Phase Ib dose-escalation stage: - Histologically or cytologically confirmed unresectable locally advanced (Stage IIIB or IIIC) or metastatic (Stage IV) NSCLC (per the **8th edition of the AJCC Cancer Staging Manual) who have progressed on or are intolerant to prior systemic therapy. - For EGFR-sensitive mutation patients:Must have received prior EGFR-TKI therapy. If only 1st/2nd-generation EGFR-TKIs were used, T790M-negative status must be confirmed. - For EGFR exon 20 insertion or other EGFR mutation patients: Must have received prior platinum-based chemotherapy. Phase Ib dose-expansion stage and Phase II Cohort 1:Histologically or cytologically confirmed unresectable locally advanced (Stage IIIB or IIIC) or metastatic (Stage IV) NSCLC (per the 8th edition AJCC staging**), either treatment-naïve or previously treated with systemic therapy. - Phase II Cohort 2 (surgical cohort): - Treatment-naïve, histologically confirmed resectable Stage II-III NSCLC (per the **8th edition AJCC staging**). - N2 definition:** Radiologically or pathologically confirmed single-station mediastinal lymph node metastasis (short-axis diameter =12 weeks, as assessed by the investigator.** 7. Adequate organ function (within 7 days prior to first study treatment), defined as: - Hematological: - Absolute neutrophil count (ANC) >=1.5 × 10?/L - Hemoglobin >=90 g/L (no red blood cell transfusion within 14 days prior to testing) - Platelets >=100 × 10?/L (no platelet transfusion within 3 days prior to testing) - No hematopoietic growth factor treatment (G-CSF, EPO, or pegylated versions) within 7 days (14 days for pegylated G-CSF/EPO) prior to testing. - Hepatic: - Total bilirubin (TBIL) 50 mL/min (calculated by Cockcroft-Gault formula) - Coagulation: - Prothrombin time (PT) =1 month prior to first study treatment. 8. For Phase II Cohort 2 (surgical cohort): - Adequate pulmonary function to tolerate planned lung resection, as assessed by a surgeon. 9. Female subjects of childbearing potential must: - Use highly effective contraception during the study and for 90 days after the last dose. - Not be breastfeeding. - Have a negative serum ß-hCG pregnancy test within 7 days before the first dose. - Non-childbearing potential is defined as: - Postmenopausal status: - Age >=60 years (natural menopause, no additional testing required), or - Age =12 months (without chemotherapy, tamoxifen, toremifene, or ovarian suppression) and FSH/estradiol levels in postmenopausal range (per local lab standards), **or**
Exclusion criteria
Exclusion criteria: 1. Participation in other therapeutic clinical trials within 28 days prior to the first study dose administration. 2. Undergoing major surgery within 28 days prior to the first study dose administration or anticipated need for major surgery during the study period. Diagnostic procedures such as thoracoscopic biopsy or mediastinoscopy may allow enrollment 7 days post-surgery. No waiting period is required after implantation of infusion ports or catheter placement. 3. Receiving radiotherapy to the lung field or whole brain within 28 days prior to the first study dose administration, or palliative localized radiotherapy within 14 days prior to the first study dose administration. 4. Use of Chinese herbal medicines with anti-tumor indications within 7 days prior to the first study dose administration. Local anti-tumor therapy (e.g., thoracic or abdominal perfusion) within 14 days or 5 half-lives (whichever is shorter) prior to the first study dose administration. 5. Receipt of anti-tumor or investigational drug therapy within 14 days or 5 times the drug half-life (whichever is longer) prior to the first study dose administration. If prior therapy involved a monoclonal antibody, treatment must be discontinued at least 2 weeks before the first dose. If prior therapy involved an oral targeted drug, treatment must be discontinued at least 5 times the drug half-life before the first dose. 6. History of another primary malignancy diagnosed or requiring treatment within the past 3 years (except for adequately treated localized basal cell or squamous cell skin cancer, or any other carcinoma in situ currently in complete remission). 7. Toxicity from prior therapy has not recovered to = Grade 1 or baseline (per NCI-CTCAE v5.0), except for alopecia, skin pigmentation, or other toxicities deemed stable by the investigator and not affecting study participation safety. 8. Requirement for strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers within 1 week prior to the first study dose administration or during the study period (see Section 10.5). 9. Presence of symptomatic central nervous system (CNS) metastases. Note:Subjects with symptomatic CNS metastases may participate if their symptoms are controlled after treatment, provided they are clinically stable for at least 4 weeks, with no evidence of new or enlarging CNS metastases, and no increase in steroid dose (equivalent to 470 ms based on three resting ECGs. • Symptomatic heart failure classified as New York Heart Association (NYHA) Class II or higher (see Chapter 10.6). • Baseline left ventricular ejection fraction (LVEF) below the institutional lower limit of normal (LLN) or <50% as assessed by echocardiography (ECHO). • Clinically significant ECG abnormalities at rest, such as complete left bundle branch block, third-degree heart block, or ventricular arrhythmias requiring antiarrhythmic therapy. • Factors increasing the risk of QTc prolongation or arrh
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Phase Ib Dose Escalation: Primary Endpoint:** Incidence of dose-limiting toxicity (DLT) events during the DLT observation period. ;Secondary Endpoint: Determination of the maximum tolerated dose (MTD) and/or recommended dose for combination therapy.;Phase Ib Expansion: Primary Endpoint:Objective response rate (ORR) as assessed by the investigator per RECIST v1.1. ;Secondary Endpoint:Recommended Phase II dose (RP2D). ;Phase II: Primary Endpoint:** ORR as assessed by the investigator per RECIST v1.1. ;Secondary Endpoint: Major pathological response (MPR) as assessed by a blinded independent pathological review (BIPR) committee. ; | — |
Secondary
| Measure | Time frame |
|---|---|
| Phase Ib Dose Escalation: Single-dose PK parameters:** Cmax, Tmax, AUC0-t, AUC0-8, CL/F, Vz/F, and t1/2. ;Multiple-dose PK parameters:Cmax, Tmax, Cmin, AUC0-tau, Rac_Cmax, Rac_AUC0-tau, CL/F, Vd/F, and t1/2.;Efficacy endpoints (investigator-assessed per RECIST v1.1):ORR, duration of response (DoR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). ;Phase Ib Expansion: Efficacy endpoints (investigator-assessed per RECIST v1.1):** DoR, DCR, PFS, and OS.;Safety endpoints: Incidence and severity of AEs (per NCI-CTCAE v5.0); clinically significant abnormalities in lab tests, vital signs, physical exams, ECG, and ECOG PS.;PK parameters: Cmax, Tmax, Cmin, AUC0-tau, Rac_Cmax, Rac_AUC0-tau; if feasible, CL/F, Vd/F, and t1/2;Phase II: Primary efficacy endpoints (investigator-assessed per RECIST v1.1):PFS, DoR, DCR, and OS.;Secondary efficacy endpoints (investigator-assessed): Event-free survival (EFS), pathological complete response (pCR), disease-free survival (DFS), ORR, OS, and surgical feasibility.;Safety endpoints:** Incidence and severity of AEs (per NCI-CTCAE v5.0); clinically significant abnormalities in lab tests, vital signs, physical exams, ECG, and ECOG PS.;PLB1004 plasma concentration:; | — |
Countries
China
Contacts
Public ContactShun Lu
Shanghai Chest Hospital
Outcome results
None listed