A Phase I Study of LX-039 Tablets

A Phase I Study of LX-039 Tablets in Postmenopausal Patients With ER+, HER2- Advanced Breast Cancer After Failure of Endocrine Therapy

This is a phase I dose escalation and expansion study in patients with ER+, HER2- advanced breast cancer to explore the tolerance, PK/PD(pharmacokinetics/pharmacodynamics) profiles and preliminary anti-tumor activity of different doses of LX-039 tablets. The trial consists of two parts, dose escalation and dose expansion. Part 1 is the dose escalation phase with initial 6 dose groups, and "3 + 3" design is used to explore MTD of the drug; Part 2 is the dose expansion phase with 2 ~ 3 doses selected for expansion according to the escalation results of Part 1, and more subjects are enrolled to further observe the tolerance and preliminary anti-tumor activity of the drug. After the completion of dose expansion, the recommended phase II dose (RP2D) will be determined after discussion based on the obtained tolerance and PK/PD data.

Inclusion Criteria:

1. Be able to read and sign the informed consent form.
2. Adult females (aged ≥18 and ≤75 years).
3. Be diagnosed with breast cancer confirmed by pathological examination.
4. Be histologically or cytologically confirmed estrogen receptor positive (ER+≥1% positive staining).
5. Be postmenopausal.
6. Subjects who have previously received endocrine therapy and obtained benefit.
7. ECOG(Eastern Cooperative Oncology Group) score ≤ 1.
8. Subjects in part2 of the study need to have measurable lesions that meet RECIST 1.1 criteria.
9. Has recovered from toxicity or injury from prior chemotherapy/radiotherapy .
10. Enough hematology and organ function.
11. Expected survival>3 months.

Exclusion Criteria:

1. Subjects with HER2-overexpressing breast cancer.
2. Subjects with known brain metastases or other central nervous system metastases that are symptomatic or untreated.
3. Patients with symptomatic advanced disease who have spread to the viscera and are at risk of life-threatening complications.
4. Subjects who received second-line or above chemotherapy.
5. Subjects with known allergy to this product or any of its components.
6. Subjects who previously used other estrogen receptor down regulators than fulvestrant.
7. Subjects who received endocrine therapy or other anti-tumor agent or radiotherapy within 4 weeks prior to study entry.
8. Subjects who received cell therapy or tumor vaccine therapy;
9. Subjects with severe immunosuppression .
10. Severe or uncontrolled disease.
11. Subjects with diseases or abnormalities that may affect the administration and absorption of drugs.
12. Subjects with other malignancy within 5 years prior to study entry.
13. Subjects with other high risks of thrombosis or require long-term use of antiplatelet drugs.
14. Subjects with history of definite neurological or psychiatric disorders in the past.
15. Subjects who are HIV(human immunodeficiency virus) antibody positive, HBsAg(hepatitis B surface antigen) positive or HCV(hepatitis C virus)antibody positive.
16. Subjects with other uncontrolled malignant/non-malignant diseases, significant laboratory abnormalities, participation in the study may increase the risk.