Locally advanced/metastatic non-small cell lung cancer positive for EGFR mutations
Conditions
Interventions
Dose-escalation group:Single and multiple administrations
Dose expansion group:Continuous administration
Sponsors
Shanghai Pulmonary Hospital
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Age >= 18 years old, male or female; 2. Patients with locally advanced/metastatic NSCLC diagnosed by histology or cytology and not suitable for surgery or radical radiotherapy; 3. Patients confirmed to be EGFR mutation-positive (only patients with EGFR ex20ins will be included in the dose expansion stage); (1) Dose escalation stage: EGFR mutation-positive patients who progress after systematic antitumor treatment or are unable to tolerate standard treatment (for example, EGFR sensitive mutation combined with T790M drug-resistant mutation needs to progress or intolerance after treatment with Oxitinib or other third-generation EGFR TKI; patients with EGFR sensitive mutation need to progress or intolerance after adequate targeted treatment and platinum-containing chemotherapy; patients with EGFR ex20ins need to progress or intolerance after platinum-containing chemotherapy); Note: for patients with EGFR ex20ins, tumor tissue samples (preferably tumor tissue samples collected after the last treatment progress) must be provided during screening, and the mutation status shall be further confirmed by the central laboratory. Admission does not need to be confirmed by the central laboratory; (2) Dose expansion stage: patients with EGFR ex20ins who progress after standard first-line chemotherapy or cannot tolerate or refuse chemotherapy; During the screening, tumor tissue samples (tumor tissue samples collected after the last treatment progress are preferred) must be provided at the same time, and the mutation status shall be further confirmed by the central laboratory. Admission does not need to be confirmed by the central laboratory; 4. Having at least one measurable or evaluable lesion (according to RECIST v1.1 [Clinical protocol Appendix 1], at least one measurable lesion is required in the expansion stage. Measurable lesions are defined as non-lymph node lesions with a maximum diameter >= 10mm or lymph node lesions with a short diameter >= 15mm measured by CT or MRI); 5. The functional level of the organ must meet the following requirements (blood transfusion, use of any cell growth factor and/or platelet raising drugs are not allowed within 14 days before obtaining the laboratory examination): (1) Absolute Neutrophil Count (ANC) >= 1.5*10^9/L Platelet count (PLT) >= 100*10^9/L Hemoglobin (Hb) >=90g/L; (2) TBIL = 45 ml/min (according to Cockcroft Gault formula); (4) INR <= 1.5 times the upper limit of normal value; (5) Serum lipase <= 1.5 times the upper limit of normal value; Serum amylase <= 1.5 times the upper limit of normal value, unless the increase of serum amylase is caused by salivary isozyme. 6. The life expectancy is not less than 12 weeks, and the ECOG score is 0 - 1 (Clinical protocol Appendix 2); 7. For premenopausal women with childbearing potential, the subjects must have blood pregnancy test within 7 days before the first dosing. With negative results and must be not lactating; Infertile women may not undergo blood pregnancy examination and contraception, but they must meet the following requirements: over 50 years old, without hormone treatment and menopause for at least 12 months, or have undergone steriliz
Exclusion criteria
Exclusion criteria: 1. Those who have previously received treatment of EGFR ex20ins inhibitors (including but not limited to Mobocertinib [TAK-788], Pocitinib) and their APIs or similar drugs in other clinical trial stages (only applicable to dose expansion stage); 2. Those who have previously received treatment ofhigh dose (exceeding the clinically approved dose) of third-generation EGFR-TKI (such as 160 mg Ositinib) (only applicable to the dose expansion stage); 3. Those who have previously participated in the treatment of EGFR monoclonal antibody or EGFR -cMET (such as JNJ-61186372) double antibody and its API or other similar drugs in the clinical trial stage (only applicable to the dose expansion stage); 4. Those who have previously received any of the following anti-tumor treatments: (1) Patients who have received more than 30% of bone marrow radiotherapy or carried out large-area irradiation (palliative radiotherapy for bone or superficial lesions is allowed and has ended 14 days before the first medication), cytotoxic chemotherapy drugs, immunotumor therapy or antitumor biological agents within 4 weeks before the first dosing; (2) Patients who received small molecule targeted antitumor drugs, traditional Chinese medicine or traditional Chinese medicine preparations with antitumor indications within 2 weeks or 5 half-life (whichever is longer) before the first dosing; 5. Major surgery (except for establishing vascular access and biopsy through mediastinoscopy or thoracoscopy) was performed within 4 weeks before the first dosing or planned during the trial; 6. Those who have participated in clinical trials and received investigational drugs or devices within 4 weeks or at least 5 half-lives of the drug (whichever is the longer) before the first dosing; 7. Those who need long-term use of medium or strong CYP3A inhibitors or inducers within 1 week before the first dosing or during the expected study period ( Clinical protocol Appendix 4); 8. Any toxicity related to previous anti-tumor treatment has not recovered to <= grade 1 (except hair loss or treatment-related grade 2 peripheral neuropathy); 9. Patients with EGFR C797S mutation; 10. Patients with spinal cord compression (symptomatic or asymptomatic) or brain metastasis (the following conditions are allowed to be enrolled: asymptomatic, stable condition, patients who do not need to use steroids for 4 weeks before the start of study treatment [if the brain metastasis has received radiotherapy or/and surgery, the radiotherapy and surgery shall be performed 1 month or longer before the first dosing]; 11. Those with obvious symptoms and unstable pleural effusion, peritoneal effusion or pericardial effusion (those with stable clinical symptoms after treatment with pleural effusion, ascites or pericardial effusion can be enrolled); 12. Those who have a history of other malignant tumors in the past, except those who have undergone radical surgery and have not recurred in 5 years, such as cervical carcinoma in situ, skin basal cell carcinoma and thyroid papillary carcinoma; 13. Those who currently have interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonia requiring steroid treatment, or have a history of these diseases; 14. Patients with cardiovascular and cerebrovascular diseases with clinical significance, including but not limited to: (1) Congestive heart failure (New York Heart Association classification [Clinical protocol Appendix 3] III-
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety Indicator; | — |
Secondary
| Measure | Time frame |
|---|---|
| Efficacy Indicator; | — |
Countries
China
Contacts
Public ContactZhou Caicun
Shanghai Pulmonary Hospital
Outcome results
None listed