First in Human Study to Evaluate the Safety, Tolerability of HH30134 in Advanced Solid Tumors

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), and to determine the maximum tolerable dose (MTD) and/or recommended phase 2 dose (RP2D) of HH30134 administered orally on a continuous once daily (QD) schedule in adults patients with advanced solid tumors.

Detailed Description
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Study population This is a global study involving multi-countries and multi-sites. Approximately 60 patients will be enrolled from participation institutions from different countries. Enrollment in dose-escalation phase must have histologically or cytologically confirmed advanced solid tumors that have recurred or progressed following the last line of therapy and at least one prior standard of care regimens, or tumor for which there is no approved therapy, or for which standard therapy is unsuitable or refused. Enrollment in dose-expansion phase will be patients with selected solid tumors including but not limited to NSCLC and mCRC.

Official Title
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A Phase I, Multi-centre, Open-Label, First in Human Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of HH30134 in Patients With Advanced Solid Tumours

Conditions
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Advanced Solid Tumors

Intervention / Treatment
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* Drug: HH30134


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of signed and dated informed consent form. Stated willingness to comply with all study procedures and availability for the duration of the study. Male and female patients ≥ 18 years of age (or having reached the age of majority according to local laws and regulations, if the age is > 18 years) Patients must have histologically or cytologically confirmed advanced solid tumors Predicted life expectancy of ≥ 3 months Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 Availability of archival tissue within three years or fresh tumor biopsy sample Patients must have adequate hepatic and renal function Exclusion Criteria: Patient has received any anticancer therapy (including chemotherapy, targeted therapy, hormonal therapy, biotherapy, immunotherapy, or other investigational agents.) within 28 days or 5 times of half-lives (whichever is shorter) prior to the first dose of the study treatment. Radical radiation therapy (including radiation therapy for over 25% bone marrow) within 4 weeks prior to the first dose of the investigational product or received local palliative radiation therapy for bone metastases within 2 weeks. Any toxicities from prior treatment that have not recovered to baseline or ≤ CTCAE v5.0 Grade 1 before the start of study treatment, with exception of hair loss. Patients who have symptomatic CNS metastasis which is neurologically unstable or those who have CNS disease requiring increase in the dose of steroid. Major surgery or had significant traumatic injury within 28 days prior to the first dose of the investigational product or has not recovered from major side effects. Known HIV infection with a history of acquired immunodeficiency syndrome (AIDS)- defining opportunity infection within the past 12months; active hepatitis B and hepatitis C. Patients whose test results meet one of the following will not be enrolled: Patient is currently receiving or has received systemic corticosteroids ≤ 2 weeks prior to starting study treatment, or who have not fully recovered from side effects of such treatment. Gastrointestinal condition which could impair absorption of study medication. Patients with clinically significant cardiovascular disease Any diseases or medical conditions, at the Investigator's discretion, that may be unstable or influence their safety or study compliance, including organ transplantation, abuse of psychotropic medication, alcohol abuse or history of drug abuse. Other serious illness or medical conditions at the Investigator's discretion, that may influence study results, including but not limited to serious infection, diabetes, cardiovascular and cerebrovascular diseases or lung disease. Pregnant or breast-feeding patients. Pregnancy refers to the state of a woman between fertilization and the end of pregnancy confirmed by a positive laboratory hCG test (> 5 mIU/mL). Breast-feeding woman can become eligible for this study if she stops breast-feeding, however, cannot restart the breast-feeding on/after the completion of the study treatment.

Ages Eligible for Study
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Minimum Age: 18 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: HH30134<br>HH30134 administered orally on a continuous once daily(QD), start from 100mg QD. | Drug: HH30134<br>* HH30134 administered orally on a continuous once daily(QD) in patients with advanced solid tumors<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose limiting toxicities(DLT) | Incidence rate of dose limiting toxicities(DLT) | 12 months | 
| Maximum Tolerated Dose | To determine the maximum tolerable dose | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic(PK) measures - Plasma concentration-time Area Under the Curve | Measure the HH30134 concentration in blood plasma as a function of time | 12 months | 
| Pharmacokinetic(PK) measures - Cmax | Measure the maximum plasma concentration of HH30134 | 12 months | 
| Pharmacokinetic(PK) measures - Tmax | Measure of time to reach maximum plasma concentration after administration of HH30134 | 12 months | 
| Pharmacokinetic(PK) measures - CL/F | Measure apparent total clearance of HH30134 from plasma after administration | 12 months | 
| Pharmacokinetic(PK) measures - Vz/F | Measure apparent volume of distribution during terminal phase after administration of HH30134 | 12 months | 
| Pharmacokinetic(PK) measures - terminal half-life(T1/2) | Measure elimination half-life of HH30134 | 12 months |