SPH5030 Tablets in Subjects With Advanced Her2-positive Solid Tumors

Study Overview
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Brief Summary
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To evaluate the safety and tolerability of SPH5030 tablets in subjects with HER2-positive advanced solid tumors

Official Title
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A Phase I Study to Evaluate the Safety, Tolerability, and Pharmacokinetic Characteristics of SPH5030 Tablets in Subjects With Advanced Her2-positive Solid Tumors

Conditions
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HER2-positive Advanced Solid Tumors

Intervention / Treatment
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* Drug: SPH5030 tablets


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged ≥18 and ≤75 years. ECOG performance status of 0 to 1. Life expectancy of more than 3 months. At least one measurable lesion exists.(RECIST 1.1) Histologically or cytologic confirmed HER2 positive metastatic solid tumor which failed prior standard treatment or have no standard treatment. Required laboratory values including following parameters: ANC: ≥ 1.5 x 109/L Plt count: ≥ 90x 109/L Hb: ≥ 90 g/L TBIL: ≤ 1.5 x ULN, ALT and AST: ≤ 2.5 x ULN and creatine clearance rate: ULN or≥ 50 mL/min Toxicity from previous antitumor therapy returned to baseline (except for residual hair loss effects) or CTCAE≤ class 1. Blood pregnancy test was negative within 3 days prior to first dose. Exclusion Criteria: Less than 4 weeks from the last radiotherapy, chemotherapy, surgery, hormone treatment, target therapy, or less than 6 weeks from the nitrosoureas or mitomycin chemotherapy. Known active infection within 2 weeks prior to baseline. Subjects with third space fluid that can not be controled by drainage or other methods. Subjects with uncontrolled or severe cardiovascular disease. Subjects with uncontrolled hypokalemia and hypomagnesemia before study entry. Subjects with severe lung disease. Subjects that are unable to swallow tablets, or dysfunction of gastrointestinal absorption. Using a potent CYP3A4 or CYP2C8 inhibitor or inducer. Steroid treatment for more than 50 days before, or in need of long-term use of steroids. Uncured other tumors within 5 years. Subjects with symptomatic CNS metastasis, pia meningeal metastasis, or spinal cord compression due to metastasis. Evidence of chronic active hepatitis B or C Uncontrolled systemic diseases, including hypertension that cannot be effectively controlled after treatment. Receive any live or attenuated live vaccine within 28 days prior to baseline. Evidence of severe allergies. Evidence of alcohol or drug abuse. Evidence of neurological or psychiatric disorders.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SPH5030 tablets<br>Subjects will take SPH5030 tablets orally on an empty stomach once or twice a day. Each subject will receive only one corresponding dose, and there were five dose groups: 50mg/ d, 100mg/ d, 200mg/ d, 300mg/ d and 400mg/ d. | Drug: SPH5030 tablets<br>* SPH5030 tablets orally once or twice daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-limiting toxicity (DLT) | Measurement of DLT of SPH5030 in all subjects | Up to 24 days | 
| Maximum tolerated dose（MTD） | Measurement of MTD of SPH5030 in all subjects | Up to 24 days | 
| Number of patients with adverse events | Adverse event type, incidence, duration, correlation with study drug | Up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum serum concentration (Cmax) of SPH 5030 | To characterize the PK (Pharmacokinetics) of SPH 5030 | Up to 2 years | 
| Time of maximum serum concentration (Tmax) SPH 5030 | To characterize the PK (Pharmacokinetics) of SPH 5030 | Up to 2 years | 
| Area under the serum concentration-time curve (AUC) of the Dosing Interval (0-14) of SPH5030 | To characterize the PK (Pharmacokinetics) of SPH 5030 | Up to 2 years | 
| Area under the serum concentration-time curve (AUC) of the Dosing Interval (0-Last) of SPH5030 | To characterize the PK (Pharmacokinetics) of SPH 5030 | Up to 2 years | 
| Area under the serum concentration-time curve (AUC) of the Dosing Interval (0-infinity) of SPH5030 | To characterize the PK (Pharmacokinetics) of SPH 5030 | Up to 2 years | 
| Accumulation ratio of maximum serum concentration (Rac_Cmax) of SPH5030 | To characterize the PK (Pharmacokinetics) of SPH 5030 | Up to 2 years | 
| Accumulation ratio of area under the serum concentration-time curve (Rac_AUC) of the Dosing Interval (0-14D) of SPH5030 | To characterize the PK (Pharmacokinetics) of SPH 5030 | Up to 2 years | 
| Terminal rate constant(λz) of SPH5030 | To characterize the PK (Pharmacokinetics) of SPH 5030 | Up to 2 years | 
| Half-life (t1/2) of SPH5030 | To characterize the PK (Pharmacokinetics) of SPH 5030 | Up to 2 years | 
| Total clearance(CL) of SPH5030 | To characterize the PK (Pharmacokinetics) of SPH 5030 | Up to 2 years | 
| Volume of distribution(Vz) of SPH5030 | To characterize the PK (Pharmacokinetics) of SPH 5030 | Up to 2 years | 
| Percentage of area under the serum concentration-time curve (AUC) obtained by extrapolation (%AUCex) of SPH5030 | To characterize the PK (Pharmacokinetics) of SPH 5030 | Up to 2 years | 
| Objective Response Rate (Investigator) | Determination of the Objective Response Rate of all patients by investigators | Up to 2 years | 
| Duration of remission (DOR) | Time from first documentation of objective response (CR or PR) to first documentation of PD/death due to any cause in absence of documented PD, based on central radiology review as per RECIST v1.1. | Up to 2 years | 
| Disease control rate (DCR) | The proportion of patients with best confirmed RECIST response of CR, PR, or duration of SD. | Up to 2 years | 
| Progression-free survival (PFS) | The interval between the dates of the first dose of trial treatment until first documentation of disease progression or death, whichever occurs first. | Up to 2 years | 
| 6-month Progression-free Survival (6mPFS) | Number of Patients Achieving 6-month Progression-free Survival | Up to 2 years |