Clinical trial NCT05378178: A PhaseⅠStudy of HS-10381 in Patients With Advanced Solid Tumors
Official title: A Phase I, Open-label, Multicenter Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Efficacy of HS-10381 in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Advanced Solid Tumor
Keywords: HS-10381
SHP2
Advanced Solid Tumor
Lead sponsor: Jiangsu Hansoh Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2022-05-18
Enrollment: 51
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Maximum Tolerated Dose of HS-10381
timeFrame: 4 weeks after initiation of treatment
Secondary outcomes:
measure: Incidence and severity of treatment-emergent adverse events
timeFrame: Baseline through study completion(28 days after last dose)
measure: Observed maximum plasma concentration (Cmax) after single dose of HS-10381
timeFrame: From pre-dose to 120 hours after single dose on Cycle 0 Day 1.
measure: Observed maximum plasma concentration (Cmax ss) after multiple dose of HS-10381
timeFrame: From pre-dose to 24 hours after the dose on Cycle 2 Day 1
measure: Apparent terminal half-life (t1/2) after single dose of HS-10381
timeFrame: From pre-dose to 120 hours after single dose on Cycle 0 Day 1
measure: Area under plasma concentration versus time curve from zero to the 24-hour sampling time (AUC0-24) after single dose of HS-10381
timeFrame: From pre-dose to 24 hours after single dose on Cycle 0 Day 1
measure: Area under plasma concentration versus time curve from zero to last sampling time (AUC0-t) after single dose of HS-10381
timeFrame: From pre-dose to 120 hours after single dose on Cycle 0 Day 1
measure: Area under the plasma concentration versus time curve from time zero to infinity (AUC0-∞) after single dose of HS-10381
timeFrame: From pre-dose to 120 hours after single dose on Cycle 0 Day 1
measure: To further evaluation of the anti-tumor activity of HS-10381 by assessment of objective response rate (ORR)
timeFrame: From the date of first occurrence of complete response (CR) or partial response (PR) on 2 consecutive occasions (≥4 weeks), until the date of disease progression or withdrawal from study，up to 2 years
Other outcomes:
Locations:
city: Xi'an
country: China
facility: West China Hospital of Sichuan University
state: Sichuan
Study officials:
affiliation: West China Hospital
name: You Lu
role: PRINCIPAL_INVESTIGATOR
References: