Back to resultsA PhaseⅠStudy of HS-10381 in Patients With Advanced Solid Tumors
Primary Purpose
Advanced Solid Tumor
Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
HS-10381
Sponsored by
About this trial
This is an interventional treatment trial for Advanced Solid Tumor focused on measuring HS-10381, SHP2, Advanced Solid Tumor
Eligibility Criteria
Inclusion Criteria:
- Men or women aged more than or equal to (≥) 18 years
- Advanced solid tumor patients confirmed by histology or cytology for who that standard treatment is invalid, unavailable or intolerable
- 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)
- ECOG performance status was 0-1 and did not deteriorate in the previous 2 weeks
- Estimated life expectancy greater than (>) 12 weeks
- 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
- Sign Informed Consent Form
Exclusion Criteria:
Treatment with any of the following:
- Previous or current treatment with drugs targeting SHP2
- Any cytotoxic chemotherapy, investigational agents or anticancer drugs within 28 days of the first dose of study drug
- 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.
- Major surgery (including craniotomy, thoracotomy, or laparotomy, etc.) within 4 weeks of the first dose of study drug.
- Known and untreated, or active central nervous system metastases.
- Existing abnormal CTCAE≥grade 2 resulted from previous treatment
- History of other malignancy
- Inadequate bone marrow reserve or organ function
- Evidence of hepatitis B virus (HBV) or hepatitis C virus (HCV), unless the hepatitis is considered to be cured, Known history of HIV
- History of hypersensitivity to any active or inactive ingredient of HS-10381.
- 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.
- Any disease or condition that, in the opinion of the investigator, would compromise the safety of the patient or interfere with study assessments.
Sites / Locations
- West China Hospital of Sichuan UniversityRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Phase I：Dose escalation
Arm Description
HS-10381 given orally QD of various dose strengths administered in 21 day dosing cycles.
Outcomes
Primary Outcome Measures
Maximum Tolerated Dose of HS-10381
To determine the MTD of HS-10381 in subjects with advanced solid tumors.
Secondary Outcome Measures
Incidence and severity of treatment-emergent adverse events
The CTCAE criteria will be used to assess adverse events on this trial.
Observed maximum plasma concentration (Cmax) after single dose of HS-10381
Cmax will be obtained after single dose of HS-10381 on Cycle 0 Day 1.
Observed maximum plasma concentration (Cmax ss) after multiple dose of HS-10381
Cmax ss will be obtained on Cycle 2 Day 1.
Apparent terminal half-life (t1/2) after single dose of HS-10381
Apparent terminal half-life is the time measured for the concentration to decrease by one half.
Area under plasma concentration versus time curve from zero to the 24-hour sampling time (AUC0-24) after single dose of HS-10381
Area under the plasma concentration versus time curve from time zero to the 24-hour sampling time at which the concentration was at or above the lower limit of quantification (LLQ).
Area under plasma concentration versus time curve from zero to last sampling time (AUC0-t) after single dose of HS-10381
Area under the plasma concentration versus time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLQ).
Area under the plasma concentration versus time curve from time zero to infinity (AUC0-∞) after single dose of HS-10381
AUC0-∞ was calculated by combining AUC0-t and AUCextra. AUCextra represents an extrapolated value obtained by Clast/ λz, where Clast is the calculated plasma concentration at the last sampling time point at which the measured plasma concentration is at or above the LLQ and λz is the apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase.
To further evaluation of the anti-tumor activity of HS-10381 by assessment of objective response rate (ORR)
Anti-tumor efficacy will be assessed by best radiographic response based on Response Evaluation Criteria in Solid Tumors at baseline (Day -28 to -1). For patients that continue on repeating 21-Day cycles after the primary evaluation period, progression will be assessed after each 6 weeks of therapy. ORR is defined as the percentage of patients with a complete response (CR) or partial response (PR) that was confirmed at a subsequent scan at least 4 weeks later, as assessed according to RECIST version 1.1.
Full Information
NCT ID
NCT05378178
First Posted
May 6, 2022
Last Updated
July 4, 2022
Sponsor
Jiangsu Hansoh Pharmaceutical Co., Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT05378178
Brief Title
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
2. Study Status
Record Verification Date
July 2022
Overall Recruitment Status
Recruiting
Study Start Date
June 8, 2022 (Actual)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
December 31, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Jiangsu Hansoh Pharmaceutical Co., Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Solid Tumor
Keywords
HS-10381, SHP2, Advanced Solid Tumor
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
51 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Phase I：Dose escalation
Arm Type
Experimental
Arm Description
HS-10381 given orally QD of various dose strengths administered in 21 day dosing cycles.
Intervention Type
Drug
Intervention Name(s)
HS-10381
Intervention Description
Each subject will receive a single dose(C0) of HS-10381 and then repeat doses(C1, C2…) for 21-day cycles. Participants may continue on study drug until disease progression, unacceptable toxicity, or other withdrawal criteria is met.
Primary Outcome Measure Information:
Title
Maximum Tolerated Dose of HS-10381
Description
To determine the MTD of HS-10381 in subjects with advanced solid tumors.
Time Frame
4 weeks after initiation of treatment
Secondary Outcome Measure Information:
Title
Incidence and severity of treatment-emergent adverse events
Description
The CTCAE criteria will be used to assess adverse events on this trial.
Time Frame
Baseline through study completion(28 days after last dose)
Title
Observed maximum plasma concentration (Cmax) after single dose of HS-10381
Description
Cmax will be obtained after single dose of HS-10381 on Cycle 0 Day 1.
Time Frame
From pre-dose to 120 hours after single dose on Cycle 0 Day 1.
Title
Observed maximum plasma concentration (Cmax ss) after multiple dose of HS-10381
Description
Cmax ss will be obtained on Cycle 2 Day 1.
Time Frame
From pre-dose to 24 hours after the dose on Cycle 2 Day 1
Title
Apparent terminal half-life (t1/2) after single dose of HS-10381
Description
Apparent terminal half-life is the time measured for the concentration to decrease by one half.
Time Frame
From pre-dose to 120 hours after single dose on Cycle 0 Day 1
Title
Area under plasma concentration versus time curve from zero to the 24-hour sampling time (AUC0-24) after single dose of HS-10381
Description
Area under the plasma concentration versus time curve from time zero to the 24-hour sampling time at which the concentration was at or above the lower limit of quantification (LLQ).
Time Frame
From pre-dose to 24 hours after single dose on Cycle 0 Day 1
Title
Area under plasma concentration versus time curve from zero to last sampling time (AUC0-t) after single dose of HS-10381
Description
Area under the plasma concentration versus time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLQ).
Time Frame
From pre-dose to 120 hours after single dose on Cycle 0 Day 1
Title
Area under the plasma concentration versus time curve from time zero to infinity (AUC0-∞) after single dose of HS-10381
Description
AUC0-∞ was calculated by combining AUC0-t and AUCextra. AUCextra represents an extrapolated value obtained by Clast/ λz, where Clast is the calculated plasma concentration at the last sampling time point at which the measured plasma concentration is at or above the LLQ and λz is the apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase.
Time Frame
From pre-dose to 120 hours after single dose on Cycle 0 Day 1
Title
To further evaluation of the anti-tumor activity of HS-10381 by assessment of objective response rate (ORR)
Description
Anti-tumor efficacy will be assessed by best radiographic response based on Response Evaluation Criteria in Solid Tumors at baseline (Day -28 to -1). For patients that continue on repeating 21-Day cycles after the primary evaluation period, progression will be assessed after each 6 weeks of therapy. ORR is defined as the percentage of patients with a complete response (CR) or partial response (PR) that was confirmed at a subsequent scan at least 4 weeks later, as assessed according to RECIST version 1.1.
Time Frame
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Men or women aged more than or equal to (≥) 18 years
Advanced solid tumor patients confirmed by histology or cytology for who that standard treatment is invalid, unavailable or intolerable
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)
ECOG performance status was 0-1 and did not deteriorate in the previous 2 weeks
Estimated life expectancy greater than (>) 12 weeks
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
Sign Informed Consent Form
Exclusion Criteria:
Treatment with any of the following:
Previous or current treatment with drugs targeting SHP2
Any cytotoxic chemotherapy, investigational agents or anticancer drugs within 28 days of the first dose of study drug
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.
Major surgery (including craniotomy, thoracotomy, or laparotomy, etc.) within 4 weeks of the first dose of study drug.
Known and untreated, or active central nervous system metastases.
Existing abnormal CTCAE≥grade 2 resulted from previous treatment
History of other malignancy
Inadequate bone marrow reserve or organ function
Evidence of hepatitis B virus (HBV) or hepatitis C virus (HCV), unless the hepatitis is considered to be cured, Known history of HIV
History of hypersensitivity to any active or inactive ingredient of HS-10381.
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.
Any disease or condition that, in the opinion of the investigator, would compromise the safety of the patient or interfere with study assessments.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
You Lu, PhD
Phone
18980601763
Email
radyoulu@hotmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
You Lu
Organizational Affiliation
West China Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
West China Hospital of Sichuan University
City
Xi'an
State/Province
Sichuan
ZIP/Postal Code
610044
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
You Lu, PhD
Phone
18980601763
Email
radyoulu@hotmail.com
12. IPD Sharing Statement
Learn more about this trial
A PhaseⅠStudy of HS-10381 in Patients With Advanced Solid Tumors
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