A Study of Hansoh (HS)-10502 in Patients With Advanced Solid Tumors

Официальное название

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

Обзор

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.

Вмешательства

• Препарат HS-10502
  HS-10502 will be administered once per day on a continuous dosing schedule starting on Cycle 1 Day 1 (C1D1) in a 28-day treatment cycle.

Первичные конечные точки

• Maximum tolerated dose (MTD) of HS-10502（Stage 1） [Срок оценки: Cycle 1 (28 days)]
• Maximum applicable dose (MAD) of HS-10502（Stage 1） [Срок оценки: Cycle 1 (28 days)]
• Efficacy of HS-10502: Objective response rate (ORR)（Stage 2） [Срок оценки: From the date of first dose until the date of disease progression or withdrawal from study, approximately 2 years]

Вторичные конечные точки (12)

• [Stage 1 and Stage 2] Incidence and severity of treatment-emergent adverse events [Срок оценки: 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: The maximum observed concentration (Cmax) of HS-10502 [Срок оценки: Cycle 1 Day 1 (each cycle is 28 days)]
• [Stage 1 and Stage 2] PK parameters: time to Cmax (Tmax) of HS-10502 [Срок оценки: Cycle 1 Day 1 (each cycle is 28 days)]
• [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 [Срок оценки: Cycle 1 Day 1 (each cycle is 28 days)]
• [Stage 1 and Stage 2] PK parameters: Maximum plasma concentration at steady state (Css, max) of HS-10502 [Срок оценки: Cycle 2 Day 1 (each cycle is 28 days)]
• [Stage 1 and Stage 2] PK parameters: time to Css, max (Tss, max) of HS-10502 [Срок оценки: 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 [Срок оценки: Cycle 2 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 [Срок оценки: Cycle 2 Day 1 (each cycle is 28 days)]
• Efficacy of HS-10502: ORR [Срок оценки: 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: disease control rate (DCR) [Срок оценки: From the date of first dose 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) [Срок оценки: From the date of CR, PR until the date of disease progression or withdrawal from study, approximately 2 years]
• [Stage 1 and Stage 2] Efficacy of HS-10502: progression free survival (PFS) (applicable for all solid tumors except prostate cancer) [Срок оценки: 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.]

Критерии участия

Критерии включения

• Males or females aged 18 - 75 years (inclusive).
• Having at least one target lesion per the RECIST v1.1.
• 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 0-1.
• 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.

Критерии исключения

• 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-10502.
• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Cancer Hospital Chinese Acedemy of Medical Sciences — Пекин

Идентификаторы

NCT: NCT05740956 · HS-10502-101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗