A PhaseⅠStudy of HS-10381 in Patients With Advanced Solid Tumors

A Phase I, Open-label, Multicenter Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Efficacy of HS-10381 in Patients With Advanced Solid Tumors

HS-10381 is a small molecular, oral potent, SHP2 inhibitor. 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-10381 in Patients With Advanced Solid Tumors.

This is a Phase 1 open-label, multicenter study to evaluate the safety, tolerability, PK and preliminary efficacy of HS-10381 in patients with advanced solid tumors by using a "3+3" dose escalation.

Inclusion Criteria:

1. Men or women aged more than or equal to (≥) 18 years
2. Advanced solid tumor 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 (>) 12 weeks
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 drugs targeting SHP2
   2. Any cytotoxic chemotherapy, investigational agents or anticancer drugs within 28 days of the first dose of study drug
   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.
   5. Known and untreated, or active central nervous system metastases.

2. Existing abnormal CTCAE≥grade 2 resulted from previous treatment

3. History of other malignancy

4. Inadequate bone marrow reserve or organ function

5. Evidence of hepatitis B virus (HBV) or hepatitis C virus (HCV), unless the hepatitis is considered to be cured, Known history of HIV

6. History of hypersensitivity to any active or inactive ingredient of HS-10381.

7. 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.

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