First-in-Human Phase I/II Study of FHND-9041 in Patients With EGFR Mutated Advanced Non-Small Cell Lung Cancer

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The following conditions make subjects ineligible to participate in this study:

1. Patients had received any cytotoxic chemotherapy in a previous regimen or clinical study within 14 days before the first dose and patients who had not previously received any EGFR-TKI were required to be enrolled in the EGFRm+ first-line treatment group.

2. The interval between the last treatment with EGFR-TKI (such as erlotinib, gefitinib, afatinib, or osimertinib) and the first administration of the study drug is less than 5 half-lives, and the specific drug involved is determined by the researcher's comprehensive consideration.

3. The interval between the last treatment with other experimental drugs or anticancer drugs and the first administration of the study drug is less than 5 half-lives

4. The patient had used the third generation EGFR-TKI drugs (such as AZD9291, CO-1686, HM61713, ASP8273, EGF816, mevalatinib, ivirinib, eflutinib, etc.) or their raw materials or generic drugs

5. A confirmed EGFR exon 20 insertion mutation was present at any time after the initial diagnosis.

6. The subject has undergone major surgery (including vascular access establishment); patients who received radiation to more than 30% of the bone marrow or large field radiation within 4 weeks before the first administration of the study treatment.

7. Subjects who are currently using or have used drugs or herbal supplements known to be strong inhibitors or inducers of CYP3A4 and CYP2C8 within 1 week (Appendix 3).

8. At the start of the study treatment, toxic reactions from previous treatment are still present and exceed grade 1 according to the Common Terminology Criteria for Adverse Events (CTCAE), except for hair loss. The previous platinum treatment-related neurotoxicity may be relaxed to grade 2.

9. Patients with symptomatic spinal cord compression or brain metastasis, stable disease without symptoms, and who do not require corticosteroid treatment within 4 weeks before the start of the study treatment, except for those who require treatment for the above conditions.

10. Any clinical evidence suggesting severe or uncontrolled systemic diseases, such as patients who are not suitable for participation in the trial as judged by the investigator or who have uncontrolled hypertension and active bleeding tendencies that may affect compliance with this clinical trial, as well as active infections, such as hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection.

11. The average corrected QT interval (QTc) obtained from 3 electrocardiogram (ECG) examinations in a resting state is \>470 msec (the first ECG indicates abnormal, and 2 repeat measurements are taken to obtain the average corrected value).

12. Various severe and clinically significant abnormalities in heart rhythm, conduction, and resting ECG morphology, such as complete left bundle branch block, third-degree atrioventricular block, second-degree atrioventricular block, PR interval \>250 msec, and so on.

13. Various factors that may increase the risk of QTc prolongation or arrhythmia events, such as heart failure, hypokalemia (except for those who have been treated with potassium supplementation and re-examined normally before the first administration), congenital long QT syndrome, a family history of long QT syndrome or unexplained sudden death before the age of 40, and various combined medications that may prolong the QT interval.

14. A history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis requiring steroid treatment, or active interstitial lung disease clinically.

15. Bone marrow reserve or organ dysfunction with the following laboratory values: absolute neutrophil count \<1.5×10\^9/L; platelet count \<100×10\^9/L; hemoglobin \<90g/L; if there is no clear evidence of liver metastasis, aspartate aminotransferase (ALT) \>2.5 times the upper limit of normal (ULN); if there is liver metastasis, ALT\>5 times ULN; if there is no clear evidence of liver metastasis, alanine aminotransferase (AST) \>2.5 times ULN; if there is liver metastasis, AST\>5 times ULN; if there is no liver metastasis, total bilirubin \>1.5 times ULN; if there is Gilbert syndrome (unconjugated hyperbilirubinemia) or liver metastasis, total bilirubin \>3 times ULN; or creatinine greater than 1.5 × ULN concurrent with creatinine clearance less than 50 mL/min (measured or calculated by Cockcroft and Gault equation); confirmation of creatinine clearance was required only when creatinine was greater than 1.5 × ULN.

16. The drug can't stability control of high blood sugar.

17. Patients who received blood transfusion within 2 weeks before screening;

18. Uncontrollable nausea and vomiting, chronic gastrointestinal diseases, and patients who cannot swallow drug preparations, and have undergone extensive intestinal resection surgery may affect the full absorption of FHND-9041.

19. Subjects with a history of hypersensitivity reactions to the excipients of FHND-9041.

20. There are other patients with malignant tumor or other malignant tumor diagnosis in recent five years before (except basal cell carcinoma or cervical breast carcinoma in situ).

21. Female subjects who are breastfeeding.

22. According to the researchers' judgment, if the subject cannot comply with the study procedures, regulations, and requirements, they cannot participate in this study.

What this study is about