临床试验/NCT05740956

NCT05740956招募中1 期

A Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of HS-10502 in Patients With Advanced Solid Tumors

Jiangsu Hansoh Pharmaceutical Co., Ltd.1 个研究点分布在 1 个国家目标入组 318 人开始时间: 2023年6月9日最近更新: 2025年6月5日

适应症

干预措施

试验速览

阶段: 1 期
状态: 招募中
发起方
入组人数: 318
试验地点: 1
主要终点: Maximum tolerated dose (MTD) of HS-10502（Stage 1）

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

HS-10502 is a Poly(ADP-ribose) polymerase 1 (PARP1)-specific selective inhibitor. The purpose if this study is to assess the safety, tolerability, pharmacokinetics (PK), and efficacy of HS-10502 in subjects with homologous recombination repair (HRR) gene mutant or homologous recombination deficiency (HRD) positive advanced solid tumors.

研究设计

研究类型: Interventional
分配方式: Na
干预模型: Single Group
主要目的: Treatment
盲法: None

入排标准

年龄范围: 18 Years 至 75 Years（Adult, Older Adult）
性别: All
接受健康志愿者: 否

入选标准

•Males or females aged 18 - 75 years (inclusive).
•Having at least one target lesion per the RECIST v1.
•For the phase Ia Cohort A: advanced solid tumor carrying HRR gene mutation with failure or intolerance or not available to the currently available Standard of care (SoC).
•For the phase Ib study:
•Cohort B: patients with HRD positive recurrent ovarian cancer with failure or intolerance or not available to SoC Cohort C: patients with HRR gene mutation advanced Human epidermal growth factor receptor 2 (HER2)-negative breast cancer with failure or intolerance or not available to SoC Cohort D: patients with HRR gene mutation advanced pancreatic cancer with failure or intolerance or not available to SoC Cohort E: patients with HRR gene mutation mCRPC with failure or intolerance or not available to SoC Cohort F: patients with HRR gene mutation colorectal cancer with failure or intolerance or not available to SoC Cohort G: patients with other HRR gene mutation or HRD positive advanced solid tumors with failure or intolerance or not available to SoC
•Eastern cooperative oncology group (ECOG) performance status was 0-
•Minimum life expectancy > 12 weeks.
•Females should be using adequate contraceptive measures and should not be breastfeeding Males should be using adequate contraceptive measures.
•Have signed Informed Consent Form.

排除标准

•Received or are receiving the following treatments:
•Previous or current treatment with two or more Poly(ADP-ribose) polymerase (PARP) inhibitors.
•Traditional Chinese medicine indicated for tumors within 2 weeks prior to the first dose of study treatment.
•Cytotoxic chemotherapeutic drugs, investigational drugs or other systematic anti-tumor therapies within 3 weeks before the first dose of study treatment; Nitrosourea or Mitomycin C within 6 weeks prior to the first dose of study treatment.
•Local radiotherapy within 2 weeks prior to the first dose of study treatment; more than 30% of bone marrow radiotherapy or large-area irradiation within 4 weeks before the first dose of study treatment.
•Presence of pleural effusion/ascites requiring clinical intervention; presence of pericardial effusion.
•Major surgery within 4 weeks prior to the first dose of study treatment.
•Presence of Grade ≥ 2 toxicities due to prior anti-tumor therapy.
•History of other primary malignancies.
•Known and untreated, or active central nervous system metastases.
•Inadequate bone marrow reserve or hepatic and renal functions.
•Myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML), or with features suggestive of MDS or AML.
•Severe, uncontrolled or active cardiovascular disorders.
•Diabetic ketoacidosis or hyperosmolar hyperglycemic state within 6 months prior to the first dose of study treatment; glycosylated hemoglobin ≥ 7.5%.
•Serious or poorly controlled hypertension.
•Any life-threatening hemorrhagic event or events requiring blood transfusion within 120 days prior to the first dose of study treatment. Clinically significant hemorrhagic symptoms or obvious hemorrhagic tendency.
•Serious infection within 4 weeks prior to the first dose of study treatment, or presence of uncontrollable active infection in the screening period.
•Having serious neurological or mental disorders.
•A history of hypersensitivity to any of the active or inactive ingredients of HS-10502 or drugs with a similar chemical structure to HS-10502 or in the same class as HS-
•Patients who may have poor compliance with the procedures and requirements of the study, as judged by the investigator.
•Patients with any condition that jeopardizes the safety of the patient or interferes with the assessment of the study, as judged by the investigator.

研究组 & 干预措施

HS-10502

Experimental

HS-10502 Tablets，PO，QD

干预措施: HS-10502 (Drug)

结局指标

主要结局

Maximum tolerated dose (MTD) of HS-10502（Stage 1）

时间窗: Cycle 1 (28 days)

MTD is defined as the previous dose level at which 2 or more out of 2-6 subjects experienced a Dose-limiting toxicity (DLT)

Maximum applicable dose (MAD) of HS-10502（Stage 1）

时间窗: Cycle 1 (28 days)

MAD is defined as follows: a) based on PK data, it is anticipated that at this dose level, the dose-exposure plateau has been reached, b) based on existing safety data, it is judged that dose escalation following this dose level will have a large safety risk or subject intolerance, or c) based on the pharmacokinetics-pharmacodynamics (PK-PD) model, it suggested that the optimal target concentration of safety and efficacy has been explored

Efficacy of HS-10502: Objective response rate (ORR)（Stage 2）

时间窗: From the date of first dose until the date of disease progression or withdrawal from study, approximately 2 years

ORR is defined as the proportion of participants with Best Overall Response (BOR) of confirmed CR or confirmed PR per RECIST v1.1 (applicable for all solid tumors except prostate cancer) or per RECIST v1.1 and PCWG3 (for prostate cancer only)

次要结局

[Stage 1 and Stage 2] PK parameters: time to Cmax (Tmax) of HS-10502(Cycle 1 Day 1 (each cycle is 28 days))
[Stage 1 and Stage 2] Efficacy of HS-10502: disease control rate (DCR)(From the date of first dose until the date of disease progression or withdrawal from study, approximately 2 years)
[Stage 1 and Stage 2] PK parameters: time to Css, max (Tss, max) of HS-10502(Cycle 2 Day 1 (each cycle is 28 days))
[Stage 1 and Stage 2] PK parameters: Minimum plasma concentration at steady state (Css, min) of HS-10502(Cycle 2 Day 1 (each cycle is 28 days))
[Stage 1 and Stage 2] PK parameters: The maximum observed concentration (Cmax) of HS-10502(Cycle 1 Day 1 (each cycle is 28 days))
[Stage 1 and Stage 2] Incidence and severity of treatment-emergent adverse events(From Cycle 1 Day 1 (C1D1) until 28 days after the final dose. A cycle is 28 days)
[Stage 1 and Stage 2] PK parameters: Maximum plasma concentration at steady state (Css, max) of HS-10502(Cycle 2 Day 1 (each cycle is 28 days))
Efficacy of HS-10502: ORR(From the date of first dose until the date of disease progression or withdrawal from study, approximately 2 years)
[Stage 1 and Stage 2] Efficacy of HS-10502: radiographic progression free survival (rPFS) (for prostate cancer only)(From the date of randomization or first dose (if randomization is not needed) until the date of disease progression or withdrawal from study, approximately 2 years)
[Stage 1 and Stage 2] Efficacy of HS-10502: ORR evaluated by RECIST v1.1 and Gynecologic Cancer Intergroup (GCIG) CA-125 (for ovarian cancer only)(From the date of first dose until the date of disease progression or withdrawal from study, approximately 2 years)
[Stage 2] Efficacy of HS-10502: overall survival (OS)(From the date of randomization or first dose (if randomization is not needed) until the documentation of death from any cause, approximately 4 years)
[Stage 1 and Stage 2] Efficacy of HS-10502: Proportion of subjects with Carbohydrate antigen (CA)-125 decreased by ≥ 50% from baseline (for ovarian cancer only)(From the date of first dose until the date of disease progression or withdrawal from study, approximately 2 years)
[Stage 1 and Stage 2] Efficacy of HS-10502: ≥ 50% PSA decrease (PSA50) response rate (for prostate cancer only)(From the date of first dose until the date of disease progression or withdrawal from study, approximately 2 years)
[Stage 1 and Stage 2] Efficacy of HS-10502: Time to PSA progression (for prostate cancer only)(From the date of first dose until the date of disease progression or withdrawal from study, approximately 2 years)
[Stage 1 and Stage 2] PK parameters: area under the concentration-time curve from time 0 to time t of last measurable concentration (AUC0-t) of HS-10502(Cycle 1 Day 1 (each cycle is 28 days))
[Stage 1 and Stage 2] PK parameters: Area under the plasma concentration-time curve over a dosing interval at steady state (AUCss) of HS-10502(Cycle 2 Day 1 (each cycle is 28 days))
[Stage 1 and Stage 2] Efficacy of HS-10502: progression free survival (PFS) (applicable for all solid tumors except prostate cancer)(From the date of randomization or first dose (if randomization is not needed) until the date of disease progression or withdrawal from study, approximately 2 years.)
Title: [Stage 1 and Stage 2] Efficacy of HS-10502: duration of response (DoR)(From the date of CR, PR until the date of disease progression or withdrawal from study, approximately 2 years)

研究者

发起方

Jiangsu Hansoh Pharmaceutical Co., Ltd.

申办方类型

Industry

责任方

Sponsor

研究点 (1)

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