Advanced non-small cell lung cancer with EGFR mutations
Conditions
Interventions
Dose expansion:The plan is to enroll approximately 20 patients per cohort in combination with other approved drugs, totaling approximately 60 patients. The dosing regimen for higher dose groups will f
Initial dosage group:The initial dosage groups are tentatively set at 200 µg ABOR2013T combined with sintilimab, and 80 µg ABOR2013T combined with sintilimab. Each of the two dosage groups in this stu
Modified "3+3" escalation cohort:The first dose level will enroll 1–6 subjects (including patients already treated at this dose level with the investigational product, totaling 3–6 subjects)
if no DLT is observed in all subjects at this dose level, escalation to the next dose level will proceed. If >=2 DLTs are observed at this dose level, enrollment at this dose will be halted, and enrol
if the final DLT rate is >=1/3, dose escalation will be terminated. Otherwise, based on the SRC’s decision, dose escalation may proceed to the next higher dose level, or additional subjects may be enr
Sponsors
The First Affiliated Hospital of Nanyang Medical College
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Age >=18 years. 2. Understand and voluntarily sign the Informed Consent Form (ICF). 3. Histopathological or cytological confirmation of NSCLC in patients harboring any one or multiple of the three EGFR mutations (L858R/19del [E746_A750del]/T790M) who are not eligible for standard of care. To explore combinations with other approved therapies, the study will be conducted in the patients who are approved according to the package insert. 4. Performance status score 0-1 according to Eastern Cooperative Oncology Group (ECOG). 5. Life expectancy >=12 weeks. 6. At least 1 measurable lesion as assessed by the investigator. 7. There are assessable tumor lesions available for tumor biopsy, and the patient must agree to provide tumor tissue samples at baseline and during treatment if feasible. If the samples had been collected prior to screening, the investigator will determine whether these can be used in lieu of a baseline biopsy. 8. Adequate organ function: Note: No blood transfusions, leukocyte-stimulating drugs (such as colony-stimulating factors), erythropoiesis-stimulating agents, or thrombopoiesis-stimulating agents have been received within 7 days prior to the examination. Laboratory Test Parameters Evaluation Criteria Hematology Absolute Neutrophil Count >=1.5×10^9/L White blood cell >=90×10^9/L Hemoglobin >=90g/L (>=5.6 mmol/L) Renal Function Serum Creatinine, or =50 mL/min Liver Function Total Bilirubin (serum) <=1.5×upper limit of normal (ULN) (except for Gilbert syndrome) AST and ALT <=2.5×ULN or <=5×ULN (if liver metastases) Coagulation Function International Normalized Ratio (INR), Activated Partial Thromboplastin Time (APTT) <=1.5×ULN 9. There is evidence that female patients are menopausal, or for women of childbearing age: negative urine pregnancy or blood pregnancy. Men of childbearing potential and women of childbearing age are willing to practice continuous effective contraceptive measures from signing the ICF to 120 days after the final dose of treatment, including abstinence or effective contraceptive measures (e.g. intrauterine or implantable contraceptive devices, oral contraceptives, injectable or embedded contraceptives, extended-release topical contraceptives, intrauterine devices [IUD], condoms [male], septum, cervical caps, etc.).
Exclusion criteria
Exclusion criteria: 1. Any other malignant tumors within the previous 5 years except for some cancers that are considered to have been recovered. Examples included basal cell carcinoma of the skin, superficial bladder cancer, breast carcinoma in situ, and cervical carcinoma in situ. 2. Patients with clinically symptomatic central nervous system tumors or metastases. Patients who have prior treatment for brain metastases and has been clinically stable and have not been on systemic steroids for at least 8 weeks before enrollment in the study. 3. History of severe heart disease, such as: symptomatic congestive heart failure (CHF) >= Grade 2 (NCI-CTCAE 5.0), New York Heart Association (NYHA) >= Grade 2 heart failure, history of transmural myocardial infarction, unstable angina pectoris, poorly controlled arrhythmia, etc. 4. Uncontrolled hypertension under two antihypertensive drugs (systolic blood pressure >= 160 mmHg or diastolic blood pressure >= 100 mmHg). 5. Uncontrolled type 2 diabetes mellitus under hypoglycemic therapy (fasting blood glucose >= 8.9 mmol/L). 6. Active autoimmune diseases and inflammatory diseases, such as systemic lupus erythematosus, psoriasis requiring systemic treatment, rheumatoid arthritis, inflammatory intestinal diseases and Hashimoto's thyroiditis. Note: Type 1 diabetes, hypothyroidism that can be controlled by replacement therapy only, skin conditions that do not require systemic treatment (e.g., vitiligo, psoriasis) can be included in the trial. 7. Any systemic antitumor therapy including investigational medication, within 14 days or within 5 half-lives of the drugs, whichever is shorter, prior to the first dose. 8. Treatment with radiotherapy within 14 days prior to the first dose. 9. Vaccination with a live or live attenuated vaccine within 30 days prior to the first dose. 10. Treatment with immunosuppressant within 14 days prior to the first dose. 11. Major surgery within 28 days prior to the first dose or non-study-related minor surgery within 7 days prior to the first dose. 12. History of immediate severe allergic reactions prior to first dose. 13. Long-term use (>= 14 days continuous use) of immunosuppressants or other immunomodulatory drugs (such as corticosteroids: prednisone or similar drugs) within 6 months, but topical medication (such as ointments, eye drops, inhalants or nasal sprays) is allowed, and the topical medication must not exceed the dose recommended in the instructions or have any signs of systemic exposure. Or have other acquired, congenital immunodeficiency diseases, or have a history of organ transplantation. 14. Thrombotic disease within 6 months prior to screening or treatment with full-dose anticoagulants. Systemic anticoagulants need to be used during intratumoral injection or biopsy. 15. Acute toxicity (CTCAE >= grade 2) caused by previous anticancer chemotherapy or immunotherapy have not been stabilized, or significant post-treatment toxicity has been observed. (Note: Chronic toxicity of previous anticancer therapy that are not expected to recover further, such as chemotherapy-induced < CTCAE grade 2 neuropathy, fatigue, alopecia, or anorexia, do not prevent participation in this study) 16. Patients with irreversible toxicity can be included based on the judgment of the investigator. 17. History of idiopathic pulmonary fibrosis or interstitial pneumonia. Having active pulmonary infections requiring anti-infective treatment prior to administration. 18. Clinicall
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of DLT (Dose-Limiting Toxicity);Incidence of adverse events;Incidence of serious adverse events;Changes in laboratory tests from baseline (biochemistry, hematology, urinalysis);Performance status (ECOG score);Progression-Free Survival;Objective Response Rate;Duration of Response;Disease Control Rate; | — |
Countries
China
Contacts
Public ContactCheng Peng
The First Affiliated Hospital of Nanyang Medical College
Outcome results
None listed