A Phase I Study of FCN-411 in Advanced Non-small Cell Lung Cancer Chinese Patients With EGFR Positive Mutation
Lung Cancer
About this trial
This is an interventional treatment trial for Lung Cancer focused on measuring advanced NSCLC, EGFR-TKI refractory
Eligibility Criteria
Inclusion Criteria:
- Age 18 years and older.
- Histological or cytological confirmed diagnosed advanced or metastatic NSCLC.
- Documentation of disease progression while on previous continuous treatment with first-line EGFR TKI; patients must have confirmation of tumor EGFR activating mutations (exon 19 del, or exon 21 ins) and T790M status by biopsy sample or optical microscopy.
- Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG).
- Have a life expectancy of at least 12 weeks.
- Have measurable disease based on RECIST v1.1. Note: previously irradiated not chosen, unless disease progression after irradiation.
Adequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values:
- Neutrophils (absolute value) ≥ 1.5×10^9/L;
- Hemoglobin ≥ 90 g/L;
- Platelet ≥ 90×10^9/L;
- Serum total bilirubin ≤ 1.5× ULN(for Patients with Gilbert Syndrome, total bilirubin ≤ 3×ULN and bilirubin ≤ 1.5×ULN should be permitted)
- Aspartate aminotransferase、alanine aminotransferase ≤ 2.5×ULN; for patients with hepatic metastases, AST、ALT ≤ 5×ULN;
- Creatinine < 1.5×ULN creatinine clearance rate≥ 45 mL/min (Cockcroft Gault for calculating)
- Female subjects have a negative urine or serum pregnancy.
Exclusion Criteria:
Treatment with any of the following:
- Treatment with an EGFR TKI within 14 days or about 5 half-lives, whichever is the longer, of the first dose of study drug;
- Any cytotoxic chemotherapy, investigational agents or anticancer drugs for the treatment from a previous treatment regimen within 14 days of the first dose of study treatment;
- Major surgery within 4 weeks of the first dose of study treatment;
- Systemic irradiation including whole brain irradiation;
- Previously treated by EGFR-TKI for T790M (for example Osimertinib).
- P-glycoprotein inducers (for example Rifampicin) or inhibitors (for example ritonavir) are required during the study.
- Any unresolved toxicities from prior therapy greater than CTCAE grade 1 at the time of starting study treatment with the exception of alopecia and grade 2, prior platinum-therapy related neuropathy.
- Meningeal metastases or CNS metastasis received intervention or malignancy related epilepsy; brain metastases without symptom are eligible.
Any serious or uncontrolled systemic disease, including but not limited to:
- Uncontrolled hypertension;
- Active hemorrhage;
- Active infections including hepatitis B, or hepatitis C;
- Human immunodeficiency virus positive;
- Child Pugh C;
- Bullous or exfoliative skin diseases;
- Severe malnutrition;
- History of keratitis or ulcerative keratitis or dry eye;
- Uncontrolled large amount of third interstitial fluid retention;
- Other serious diseases or mental disorders or laboratory abnormalities.
Cardiac function and disease are consistent with the following:
- QTc> 470 milliseconds from 3 electrocardiograms (ECGs);
- Any clinically important abnormalities in rhythm;
- Any factors that increase the risk of QTc prolongation;
- Congestive heart failure ≥ grade 3 by New York Heart Association (NYHA);
- Previous history with interstitial lung disease、drug-induced interstitial lung disease or radiation pneumonitis require hormone therapy, or other active interstitial lung diseases required treatments.
Lung function met one of the following criteria:
- Oxygen saturation ≤ 88%;
- The first second forced expiratory volume< 50% of the predicted value;
- Diffusion capacity for CO < 50% of the predicted value.
- Dysphagia, or active digestive system diseases or medical conditions potentially affect FCN-411 absorption.
- Hypersensitivity to FCN-411 or similar compounds or excipients.
- Pregnant or lactating women.
Sites / Locations
- Cancer hospital chinese academy fo medical sciencedRecruiting
Arms of the Study
Arm 1
Arm 2
Experimental
Experimental
Dose escalation cohort of FCN-411
Dose expansion cohort of FCN-411
FCN-411 will be orally administrated at five sequential dose levels, which are 4 mg, 8 mg, 16 mg, 24 mg, and 32 mg. Patients must be diagnosed with locally advanced or metastatic NSCLC who have progressed following prior therapy with an EGFR TKI agent (+/- additional chemotherapy regimens). Participants will receive FCN-411 monotherapy once daily (QD) for sequential 21-day cycles.
FCN-411 will be orally administrated at MTD. Patients must be diagnosed with locally advanced or metastatic NSCLC who have progressed following prior therapy with an EGFR TKI agent (+/- additional chemotherapy regimens). Participants will receive FCN-411 monotherapy once daily (QD) for sequential 21-day cycles.