Patient case: 54-year-old female with non-small cell lung cancer; genetic feature: EGFR (D770N)

Clinical trial: A Phase I Study of FCN-411 in Advanced Non-small Cell Lung Cancer Chinese Patients With EGFR Positive Mutation

Summary: This phase I trial with dose-escalation stage and dose-expansion stage is the first-in-human study of FCN-411, a drug being developed for treatment of advanced cancers. The initial purpose of the study is to determine the maximum tolerated dose (MTD) and the recommended phase 2 dose (RP2D) of FCN-411 monotherapy in EGFR-positive mutation non-small cell lung cancer chinese patients. The study will also provide early information on how the body handles the drug (pharmacokinetics) and on the anti-tumor activities of FCN-411.


Eligibility: Inclusion Criteria:
  1. Age 18 years and older.
  2. Histological or cytological confirmed diagnosed advanced or metastatic NSCLC.
  3. 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 ) and T790M status by biopsy sample or optical microscopy.
  4. Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG).
  5. Have a life expectancy of at least 12 weeks.
  6. Have measurable disease based on RECIT1.1. Note: previously irradiated not chosen, unless disease progression after irradiation.
  7. Adequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values:
  1. Neutrophils (absolute value) ≥ 1.5×109/L;
  2. Hemoglobin ≥ 90 g/L;
  3. Platelet ≥ 90×109/L;
  4. Serum total bilirubin ≤ 1.5× ULN（for Patients with Gilbert Syndrome, total bilirubin ≤ 3×ULN and bilirubin ≤ 1.5×ULN should be permitted）
  5. Aspartate aminotransferase、alanine aminotransferase ≤ 2.5×ULN; for patients with hepatic metastases, AST、ALT ≤ 5×ULN;
  6. Creatinine < 1.5×ULN creatinine clearance rate≥ 45 mL/min (Cockcroft Gault for calculating)
  8. Female subjects have a negative urine or serum pregnancy.
  Exclusion Criteria:
  1. Treatment with any of the following:
  1. Treatment with an EGFR TKI within 14 days or about 5x half-life, whichever is the longer, of the first dose of study drug;
  2. 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;
  3. Major surgery within 4 weeks of the first dose of study treatment;
  4. Systemic irradiation including whole brain irradiation;
  5. Previously treated by EGFR-TKI for T790M (for example Osimertinib).
  2. P-glycoprotein inducers (for example Rifampicin) or inhibitors (for example ritonavir) are required during the study.
  3. 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.
  4. Meningeal metastases or CNS metastasis received intervention or malignancy related epilepsy; brain metastases without symptom are eligible.
  5. Any serious or uncontrolled systemic disease, including but not limited to:
  1. Uncontrolled hypertension;
  2. Active hemorrhage;
  3. Active infections including hepatitis B, or hepatitis C;
  4. Human immunodeficiency virus positive;
  5. Child Pugh C;
  6. Bullous or exfoliative skin diseases;
  7. Severe malnourishment;
  8. History of keratitis or ulcerative keratitis or dry eye;
  9. Uncontrolled large amount of third interstitial fluid retention;
  10. Other serious diseases or mental disorders or laboratory abnormalities.
  6. Cardiac function and disease are consistent with the following:
  1. QTc> 470 milliseconds from 3 electrocardiograms (ECGs);
  2. Any clinically important abnormalities in rhythm;
  3. Any factors that increase the risk of QTc prolongation;
  4. Congestive heart failure ≥ grade 3 by New York Heart Association (NYHA);
  7. 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.
  8. Lung function met one of the following criteria:
  1. Oxygen saturation ≤ 88%;
  2. The first second forced expiratory volume< 50% of the predicted value;
  3. Diffusion capacity for CO < 50% of the predicted value.
  9. Dysphagia, or active digestive system diseases or medical conditions potentially affect FCN-411 absorption.
  10. Hypersensitivity to FCN-411 or similar compounds or excipients.
  11. Pregnant or lactating women.

Relevance to patient case: possibly relevant