A Study of SC10914 in Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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SC10914 is a potent selective PARP-1 and PARP-2 inhibitor. This study aims to determine the safety , tolerability , pharmacokinetic/pharmacodynamics profile of increasing doses of SC10914 when administered orally to patients with advanced solid tumors. Furthermore, the safety and efficacy of SC10914 in patients with advanced solid tumors and negative expression of ATM or BRCA1 or BRCA2 mutation will be evaluated in expanded cohorts to establish the Recommended Phase 2 Dose(RP2D).

Official Title
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Phase 1 Study to Assess the Safety, Tolerability, Pharmacokinetics/ Pharmacodynamics and Preliminary Efficacy of SC10914 in Patients With Advanced Solid Tumors

Conditions
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Advanced Solid Tumors

Intervention / Treatment
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* Drug: SC10914


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed written informed consent Aged 18-70 years Dose escalation study: Subjects diagnosed with advanced solid malignancies who are refractory to standard therapies or for which no standard therapy exists/Dose Expansion study: Subjects diagnosed with advanced solid malignancies who are refractory to standard therapies or for which no standard therapy exists and negative expression of ATM or BRCA1 or BRCA2 mutation Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 Have measurable lesion exists(RECIST 1.1) Life expectancy≥3 months Have adequate bone marrow, hepatic and renal functions Exclusion Criteria: Allergic constitution or hypersensitivity to investigational drugs or relevant drug Patients who received any previous treatment with a PARP inhibitor Patients accepted anti-cancer therapy including chemotherapy, radiotherapy, endocrinotherapy, immunotherapy, Chinese herbal treatment or other investigational drugs within 4 weeks prior to trial entry (or a longer period depending on the defined characteristics of the drugs used eg,. 6 weeks for mitomycin C or nitrosourea) With serious pre-existing medical conditions, such as significant cardiovascular disease and psychogenic disorders With family history of long QT syndrome or QTc ≥ 450 ms With persistent CTCAE ≧grade 2 toxicities (excluding alopecia) caused by prior medication With symptomatic brain metastases Pregnancy or lactation With Hepatitis B or C or human immunodeficiency virus infections

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SC10914<br>SC10914 Dose Escalation： Dose Level 1：30mg(QD) Dose Level 2：60mg(QD) Dose Level 3：120mg(QD) Dose Level 4：200mg(QD) Dose Level 5：100mg(BID) Dose Level 6：300mg(QD) Dose Level 7：150mg(BID) Dose Level 8：400mg(QD) Dose Level 9：200mg(BID) Dose Expansion： Receiving SC10914 in one of three dosage regimens(low, middle or high dose-level and QD or BID) based on the assessment of dose escalation study. | Drug: SC10914<br>* SC10914 will be administered orally.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose Escalation Study: Maximum-tolerated Dose (MTD) of SC10914 | In dose escalation study, SC10914 will be administered to patients with advanced solid tumors. MTD is defined as the maximum dose level at which no more than one subject out of three experiences has a dose-limiting toxicity (DLT) within 30 days after accepting SC10914. | 30 days | 
| Dose Expansion Study: Recommended Phase II Dose(RP2D) of SC10914 | In dose expansion study,SC10914 will be administered to patients with advanced solid tumors and negative expression of ATM or BRCA1 or BRCA2 mutation.RP2D will be defined based on all available safety, pharmacokinetics(PK), pharmacodynamics(PD), and efficacy data collected after the start of SC10914 treatment. | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-related adverse events (AEs) as assessed by NCI-CTCAE v4.03 |  | 8 weeks | 
| Area under the concentration-time curve (AUC) |  | 4 weeks | 
| Time to reach maximum concentration (Tmax) |  | 4 weeks | 
| Maximum Concentration (Cmax) |  | 4 weeks | 
| Trough Concentration (Ctrough) |  | 4 weeks | 
| Elimination Half-Life (T½) |  | 4 weeks | 
| Clearance (CL) |  | 4 weeks | 
| Volume of Distribution (Vd) |  | 4 weeks | 
| Evaluation of the effects of PARP inhibition of SC10914 by the peripheral blood mononuclear cells（PBMC） |  | 8 weeks | 
| Evaluation of the antitumor effects of SC10914 as measured by overall response rate (ORR) |  | 8 weeks | 
| Evaluation of the antitumor effects of SC10914 as measured by disease control rate (DCR) |  | 8 weeks | 
| Evaluation of the antitumor effects of SC10914 as measured by progression free survival (PFS) |  | 8 weeks | 
| Evaluation of the antitumor effects of SC10914 as measured by duration of response (DOR) |  | 8 weeks | 
| Evaluation of the antitumor effects of SC10914 as measured by time to progression (TTP) |  | 8 weeks | 
| Evaluation of the antitumor effects of SC10914 as measured by overall survival (OS) |  | Baseline until death | 
| Evaluation of the antitumor effects of SC10914 as measured by tumor markers CA-125 as assessed by Gynecologic Cancer Intergroup(GCIG) |  | 8 weeks | 
| Evaluation of the antitumor effects of SC10914 as measured by tumor markers PSA as assessed by Prostate-Specific Antigen Working Group(PSAWG) |  | 8 weeks |