A Study of SYHA1807 in Subjects With Extensive-Stage Small Cell Lung Cancer

Study Overview
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Brief Summary
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This is a phase I, open-label, multi-center, non-randomized, 2-part first time inhuman (FTIH) study for SYHA1807. Part 1 is a dose escalation phase to determine the recommended phase 2 dose (RP2D) for SYHA1807 based on the safety, tolerability and pharmacokinetics (PK) profiles observed after oral administration of SYHA1807. The dose escalation study will be performed according to the 3+3 design. Once RP2D is identified, an expansion cohort (Part 2) of up to 12 40 subjects will be enrolled to further evaluate the clinical activity and tolerability of SYHA1807 in subjects with extensive-stage Small Cell Lung Cancer (SCLC).

Official Title
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A Phase I, Open-label, Dose Escalation Study to Investigate the Safety, Pharmacokinetics and Clinical Activity of SYHA1807 Given Orally in Subjects With Extensive-Stage Small Cell Lung Cancer

Conditions
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Extensive-Stage Small Cell Lung Cancer

Intervention / Treatment
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* Drug: SYHA1807
* Drug: SYHA1807


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed diagnosis of advanced SCLC; ECOG(Eastern Cooperative Oncology Group) performance status of 0 or 1; Measurable disease according to RECIST v1.1; Recovered from all toxicities associated with previous treatments; Life expectancy ≥ 3 months; Adequate organ function; Use of reliable contraceptive methods; Signed informed consent from the patient; Exclusion Criteria: Patients with primary malignant tumor other than small cell lung cancer; Identified central nervous system metastasis (such as brain metastasis or meningeal metastasis); Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage; Inadequate washout period for previous anti-tumor therapy; Previous treatment with any LSD1(lysine specific demethylase 1) inhibitor; Unable to swallow oral medications; History of serious systemic diseases; History of serious autoimmune diseases； HIV positive; Pregnant or lactating women.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Escalation Cohort<br>Five dose levels will be tested according to the 3 + 3 dose-escalation design. The dose-limiting toxicity (DLT) will be assessed from the first administration of SYHA1807 to the end of the first cycle (28 days). | Drug: SYHA1807<br>* Escalation Cohort Administration: Orally<br>|
| Experimental: Dose Expansion Cohort<br>Once the RP2D has been determined, an expansion cohort of up to 12 40 subjects will be enrolled in order to better characterize the clinical activity and safety profile of the RP2D. | Drug: SYHA1807<br>* Dose Expansion Cohort Administration: Orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1:Number of Participants With Adverse Events | An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. | Through study completion, an average of 2 year | 
| Part 1:Number of Participants With Serious Adverse Events (SAEs) | SAE is defined as any untoward medical occurrence that, at any dose results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability, is a congenital anomaly/birth defect, other situations and is associated with liver injury or impaired liver function. | Through study completion, an average of 2 year | 
| Part 1:Number of Participants With Dose Limiting Toxicities (DLT) | An event was considered a DLT if it occurs within the first 28 days of treatment. | Through study completion, an average of 2 year | 
| Number of Participants With Dose Reduction or Delays | The number of participants who had any dose reduction or delay have been presented. All dose reductions were due to AEs. | Through study completion, an average of 2 year | 
| Number of Participants Withdrawn Due to Toxicities | Participants were monitored from start of the study till the development of toxicity. The data for number of participants withdrawn due to toxicities has been presented. | Through study completion, an average of 2 year | 
| Number of Participants With Change in Clinical Chemistry Toxicity Grade From Baseline | Baseline value was defined as the most recent, non-missing value from a central laboratory prior to or on the first dose of study treatment. Change from Baseline was defined as any visit value minus Baseline value. The number of participants with any grade increase in hematology parameters have been presented. | Through study completion, an average of 2 year | 
| Number of Participants With Critical Changes in Values of Vital Signs in Response to Drug | Vital sign measurements includes systolic blood pressure (SBP), diastolic blood pressure (DBP), temperature, respiration rate and heart rate. The number of participants with critical changes in values of vital signs in response to drug have been presented. | Through study completion, an average of 2 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-infinity]) Following Single Dose Administration of SYHA1807 | The analysis was performed on Pharmacokinetic Population which included all participants in the All Treated Population for whom a pharmacokinetic sample was obtained and analyzed. | Through study completion, an average of 2 year | 
| Maximum Observed Plasma Concentration (Cmax) Following Single and Repeat Dose Administration of SYHA1807 | The analysis was performed on Pharmacokinetic Population which included all participants in the All Treated Population for whom a pharmacokinetic sample was obtained and analyzed. | Through study completion, an average of 2 year | 
| Time to Reach Cmax (Tmax) Following Single and Repeat Dose Administration of SYHA1807 | The analysis was performed on Pharmacokinetic Population which included all participants in the All Treated Population for whom a pharmacokinetic sample was obtained and analyzed. Tmax is the time to reach Cmax, determined directly from the concentration-time data. | Through study completion, an average of 2 year | 
| Apparent Terminal Phase Elimination Rate Constant (λz) Following Single and Repeat Dose Administration of SYHA1807 | The analysis was performed on Pharmacokinetic Population which included all participants in the All Treated Population for whom a pharmacokinetic sample was obtained and analyzed. | Through study completion, an average of 2 year | 
| Apparent Terminal Phase Half-life (T1/2) Following Single and Repeat Dose Administration of SYH1A1807 | The analysis was performed on Pharmacokinetic Population which included all participants in the All Treated Population for whom a pharmacokinetic sample was obtained and analyzed. | Through study completion, an average of 2 year | 
| Number of Participants Achieving Disease Control Rate at Week 6、12 | Clinical response was assessed by the investigator using computer tomography or magnetic resonance imaging scans. Clinical response was defined as disease control rate ,CR(Complete response)+PR(Partial response)+SD(Stable disease),based on RECIST version 1.1 at Week 6、12. | Through study completion, an average of 2 year |