Phase I Study of the HS-10352 in Patients With Advanced Breast Cancer

A Phase 1, Open-label, Multicenter Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Efficacy of Single and Multiple Doses of Oral Administration of HS-10352 in Patients With Locally Advanced or Metastatic Breast Cancer Progressing After Standard Therapy

HS-10352 is a highly potent and selective small molecule inhibitor of phosphoinositide 3-kinase (p110α). In preclinical studies, it demonstrated strong activity against PI3K p110α in vitro and in vivo, and inhibited tumor cell growth. The first-in-human trial is conducted to assess the maximum tolerated dose (MTD) and dose limiting toxicity (DLT), to evaluate the pharmacokinetics, safety and preliminary anti-tumor activity of HS-10352 at single dose and multiple doses.

This is a phase I, open-label, multicenter study to evaluate safety, tolerability, pharmacokinetics, and efficacy of single and multiple doses of oral administration of HS-10352 in patients with locally advanced or metastatic breast cancer with hormone receptor (HR) positive and epidermal growth factor receptor 2 (HER2) negative who have progressed following prior therapy. There is a dose-escalation study, which is designed to evaluate the safety, tolerability, and pharmacokinetics of single dose and multiple doses of HS-10352 given once every day (QD). An alternative dosing schedule of twice every day (BID) may be investigated if the drug clearance of HS-10352 is faster than anticipated.

All patients will be carefully followed for adverse events during the study treatment and for 28 days after the last dose of study drug. Subjects of this study will be permitted to continue therapy with assessments for progression once every 8 weeks, if the product is well tolerated and the subject has stable disease or better. As the disease progresses, survival follow-up is recommended bimonthly.

Inclusion Criteria:

1. Men or women aged more than or equal to (≥) 18 years, and less than (<) 75 years.
2. HR+ HER2- locally advanced or metastatic breast cancer patients confirmed by histology or cytology for who that standard treatment is invalid, unavailable or intolerable.
3. Patients have at least one target lesion according to RECEST 1.1. The requirements for target lesions are: measurable lesions without local treatment such as irradiation, or with definite progress after local treatment, with the longest diameter ≥ 10 mm in the baseline period (in case of lymph nodes, the shortest axis ≥ 15 mm is required)
4. ECOG performance status was 0-1 and did not deteriorate in the previous 2 weeks.
5. Estimated life expectancy greater than (>) three months.
6. Females should be using adequate contraceptive measures throughout the study; should not be breastfeeding at the time of screening, during the study and until 3 months after completion of the study; and must have evidence of non-childbearing potential.
7. Sign Informed Consent Form.

Exclusion Criteria:

1. Treatment with any of the following:

   1. Previous or current treatment with PI3K, AKT or mTOR inhibitors.
   2. Any cytotoxic chemotherapy, investigational agents within 21 days of the first dose of study drug; anticancer drugs which have been received within 14 days before the first administration.
   3. Radiotherapy with a limited field of radiation for palliation within 2 weeks of the first dose of study drug, or patients received more than 30% of the bone marrow irradiation, or large-scale radiotherapy within 4 weeks of the first dose.
   4. Major surgery (including craniotomy, thoracotomy, or laparotomy, etc.) within 4 weeks of the first dose of study drug.

2. Inadequate bone marrow reserve or organ function.

3. Uncontrolled pleural effusion or ascites or pericardial effusion.

4. Known and untreated, or active central nervous system metastases.

5. History of primary or secondary diabetes.

6. History of acute or chronic pancreatitis

7. Refractory nausea, vomiting, or chronic gastrointestinal diseases, or inability to swallow the study drug that would preclude adequate absorption of HS-10352.

8. History of hypersensitivity to any active or inactive ingredient of HS-10352 or to drugs with a similar chemical structure or class to HS-10352.

9. Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions, and requirements.

10. Any disease or condition that, in the opinion of the investigator, would compromise the safety of the patient or interfere with study assessments.