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

• Status: Recruiting
• Trial end date: 2021-12-20
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Ahon Pharmaceutical Co., Ltd.
• Collaborator: Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Criteria

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 ins) 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 RECIST v1.1. 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) ≥ 1.5×10^9/L;

2. Hemoglobin ≥ 90 g/L;

3. Platelet ≥ 90×10^9/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 5 half-lives, 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 malnutrition;

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.