MEK Inhibitor Combined With Anlotinib in the Treatment of KRAS-mutated Advanced Non-small Cell Lung Cancer

• Status: Not yet recruiting
• Trial end date: 2023-08-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a phase I, exploratory study. The study plans to enroll 30 eligible patients to receive MEK inhibitor combined with anlotinib. Tumor assessments will be performed at Screening with follow-up at Week 4 ±1 week from the date of the first cycle treatment, and then every 4 weeks ±1 week until confirmed objective disease progression. Patients will participate in safety follow-up after the first course of treatment, until within 3 months after stopping the drug due to PD or toxicity. Blood samples will be collected at baseline and each periodic assessment for biomarker analysis and screening.

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

Details

• Lead Sponsor: Shanghai Chest Hospital
• Treatments: Trametinib

Criteria

Inclusion Criteria:

• For inclusion in the study subjects should fulfill the following criteria:

1. Age: 18-75 years old, both male and female;

2. ECOG score 0 or 1 point;

3. According to the eighth edition of the International Anti-Cancer Alliance/American Cancer Staging System, patients with stage IIIB-IV non-small cell lung cancer diagnosed by histopathology or cytology

4. Patients with KRAS gene mutation confirmed by the central laboratory;

5. Before the study drug is administered, the previous chemotherapy, immunotherapy or radiotherapy must have been completed for at least 4 weeks, and all related toxic reactions (except for hair loss) have been restored before the study drug is administered (recovered to ≤ Grade 1 or Baseline level);

6. Must be willing to provide tumor tissue samples archived or freshly obtained within 6 months before signing the informed consent form, and the tissue sections should not be less than 6-8 pieces (if less than 6 pieces need to be negotiated with the sponsor, they can be included in the group after consent)

7. According to the RECIST v1.1 standard, patients must have measurable target lesions that can be examined by CT or MRI

8. Patients need to meet the following laboratory test results, which need to be completed within 14 days before the first administration: 1) Routine blood test (no blood transfusion or correction with hematopoietic stimulating factor drugs within 14 days before screening): Hemoglobin ( HB) ≥90 g/L; Absolute neutrophil count (ANC) ≥2.0×109/L; Absolute lymphocyte count (LC) ≥0.5×109/L; Platelet count (PLT) ≥100×109/ L; White blood cell count (WBC) ≥4.0×109/L and ≤15×109/L. 2) Biochemical examination (no blood transfusion or albumin within 14 days before screening): AST and ALT≤2.5 ULN (if there is tumor liver metastasis, ≤5 ULN); ALP≤2.5 ULN (if there is tumor bone metastasis, ≤5 ULN) ; TBiL≤1.5 ULN; ALB≥30 g/L; Cr≤1.5 ULN, and creatinine clearance (CrCL)≥60 mL/min (Cockcroft-Gault formula); APTT≤1.5 ULN, and INR or PT≤1.5 ULN ( Did not receive anticoagulation therapy);

9. Women of childbearing age must undergo a serum pregnancy study within 3 days before the first medication, and the result is negative. Women of childbearing age and men whose partners are women of childbearing age must agree to use high-efficiency methods of contraception during the study period and within 180 days after the last administration of the study drug

10. Volunteer to participate in clinical research, good compliance, and signed informed consent.

Exclusion Criteria:

• Subjects must not enter the study if any of the following exclusion criteria are fulfilled:

1. Have previously received specific MEK inhibitors or treatment programs containing Anlotinib;

2. Those who have participated in other clinical trials and used other trial-related drugs within 4 weeks before the start of study administration;

3. Concomitant treatment with other anti-tumor drugs during the study period (hormone therapy is acceptable);

4. Patients with active central nervous system (CNS) damage (ie, imaging instability, symptomatic damage). Note: For patients receiving stereotactic radiotherapy or surgical treatment, no brain disease progression during the period of 3 months or more can be selected;

5. Within 4 weeks before the start of the study treatment, the occurrence of grade 3 bleeding symptoms specified in the National Cancer Institute's Common Terminology Standards for Adverse Events (NCI CTCAE v4.03);

6. Concomitant diseases or infectious diseases that have not been controlled;

7. For pre-menopausal women (postmenopausal women must have been menopausal for at least 12 months to be considered infertile) serum pregnancy test results are positive or judged by the investigator, during the study period and at least 30 days after the last administration of the study drug, Willing to become pregnant, breastfeeding, or unwilling to use effective contraceptive measures (including female spouses of male subjects of childbearing age);

8. Other severe, acute, or chronic clinical or mental diseases or laboratory abnormalities that may increase the risk of participating in research and research medication, or may interfere with the interpretation of research results.

9. There are EGFR mutations and ALK fusions;

10. Intravenous or oral drugs that are being received and cannot be stopped at least 2 weeks before the start of the study treatment and during the study period and the protocol forbidden to affect CYP isoenzymes (strong inducers, strong inhibitors and enzyme substrates of CYP2C9 and CYP 2C19) (Appendix 17-3, 17-4);

11. Inability to swallow capsules or intractable nausea and vomiting, malabsorption, extracorporeal bile shunt, or any significant small bowel resection that may prevent the full absorption of the study drug;

12. ECG QTcB ≥480msec corrected by Bazetts formula at screening or a history of congenital long QT syndrome;

13. Within 6 months before study administration, any of the following conditions occurred: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, severe arrhythmia requiring medication , Uncontrollable hypertension, cerebrovascular accident, transient ischemic attack or symptomatic pulmonary embolism;

14. Active/chronic human immunodeficiency virus (HIV), syphilis, hepatitis C virus (HCV) or hepatitis B virus (HBV) infection. Active/chronic HBV infection is defined as HBsAg or HBV DNA positive, and chronic HCV is defined as anti-HCV antibody or HCV RNA positive;

15. Interstitial lung disease or interstitial pneumonia, including clinically significant radiation pneumonia (that is, affecting daily life activities or requiring intervention and treatment);

16. Medical history of allogeneic bone marrow transplantation or organ transplantation;

17. Existence of other active malignant tumors, or a history of other malignant tumors other than NSCLC in the past 5 years, excluding any type of carcinoma in situ, skin basal cell carcinoma or squamous cell carcinoma that has been cured in the past

18. Known to have chronic liver disease;