EGFR mutation-positive locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC)
Conditions
Interventions
Experimental Group:Single dose: Fasting, oral administration, as a single dose, taken with warm water.
Multiple doses: Fasting, oral administration, as a single dose, taken with warm water, once dail
Sponsors
Shanghai East Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Male or female, aged >=18 years and =12 weeks. 9. Adequate hematologic and organ function, and no hematopoietic growth factors, blood transfusions, or platelet (PLT) therapy within 2 weeks before sampling for laboratory tests. (1) Hematologic Function:Absolute neutrophil count (ANC) >= 1.5×10^9/L;Platelet count (PLT) >= 100×10^9/L;Hemoglobin (HGB) >=9.0 g/dL; (2)Hepatic Function:Total bilirubin (TBIL) 1.5 × ULN, creatinine clearance =50 mL/min [Creatinine clearance calculated using the Cockcroft-Gault formula (see Appendix 2: Cockcroft-Gault Formula)] (4)Coagulation Panel Note: For subjects receiving anticoagulant therapy, the investigator will determine whether the international normalized ratio (INR) and activated partial thromboplastin time (APTT) are within a safe therapeutic range. INR <= 1.5×ULN;APTT <= 1.5×ULN. 10. Women of childbearing potential (WOCBP) and male subjects of reproductive potential with a WOCBP partner must use highly effective contraception throughout the study (from signing the ICF until 6 months after the last dose of HJ-004-02 tablets, see Appendix 3: Contraceptive Measures, Definitions, and Requirements for Women of Childbearing Potential) and are prohibited from donating sperm or eggs. WOCBP must have a negative serum pregnancy test result within 7 days before the first dose of HJ-004-02 tablets.
Exclusion criteria
Exclusion criteria: 1.Have received any of the following treatments: (1) Have received EGFR-TKI therapy within 8 days before the first dose of HJ-004-02 tablets, including but not limited to osimertinib, afatinib, gefitinib, or erlotinib; (2) Have received immunotherapy or biological therapy within 4 weeks before the first dose of HJ-004-02 tablets; (3) Have received radiotherapy within 4 weeks before the first dose of HJ-004-02 tablets (Note: Subjects who have completed palliative radiation at least 2 weeks before the first dose of HJ-004-02 tablets may be enrolled); (4) Have received herbal or traditional Chinese medicine treatment with anti-tumor indications within 2 weeks before the first dose of HJ-004-02 tablets; (5) Have received chemotherapy or other anti-tumor drug therapy within 4 weeks before the first dose of HJ-004-02 tablets; (6) Prior treatment with other PROTAC drugs targeting EGFR mutations. 2. Participation in an investigational drug study with treatment or use of an investigational device within 4 weeks before the first dose of HJ-004-02 tablets. 3. Anticipated need for any other form of anti-tumor therapy during the study. 4. Toxicity from prior therapy has not resolved to Grade 1 (CTCAE v5.0) prior to the first dose of HJ-004-02 tablets. 7. History of severe dermatosis prior to the first dose of HJ-004-02 tablets, or subjects with dermatosis > Grade 1 (CTCAE v5.0) prior to the first dose of HJ-004-02 tablets, or adverse reactions from prior anti-tumor therapy have not resolved to =Grade 2 requiring systemic intravenous antibiotic therapy within 2 weeks before the first dose of HJ-004-02 tablets. 13. Subjects with a history of allergy to the active
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of dose-limiting toxicities (DLTs) during the DLT observation period;Incidence and severity of adverse events (AEs);Abnormalities in laboratory tests, physical examinations, vital signs, echocardiograms, Eastern Cooperative Oncology Group (ECOG) performance status (PS) scores, and 12-lead electrocardiograms (ECGs).; | — |
Secondary
| Measure | Time frame |
|---|---|
| PK parameters of HJ-004-02 and its metabolites (if applicable) after a single administration;The PK parameters of HJ-004-02 and its metabolites (if applicable) after multiple administrations;ORR;DCR;DOR;PFS;TTP;Ldentification of metabolites of HJ-004-02 in plasma;The changes of ctDNA; | — |
Countries
China
Contacts
Public ContactCaicun Zhou
Shanghai East Hospital
Outcome results
None listed