HS-10502 Combination Treatment in Patients With Advanced Solid Tumors

Официальное название

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

Обзор

HS-10502 is a PARP1-specific selective inhibitor. The purpose if this study is to assess the safety, tolerability, pharmacokinetics (PK), and efficacy of HS-10502 Combination Treatment in subjects with advanced solid tumors.

Подробное описание

This is a phase I, multicenter, open-label clinical study to evaluate the safety, tolerability, PK, and efficacy of oral HS-10502 combination treatment in subjects with advanced solid tumors. The study will be divided into phase Ia (dose escalation) and phase Ib (dose expansion). The dose-escalation study will be conducted to evaluate the safety, tolerability, PK profile, and efficacy, as well as to determine the maximum tolerable dosage (MTD) or maximum applicable dose (MAD) of HS-10502 in combination with other antitumor agents (Enzalutamide, Rezvilutamide,Abiraterone,HS-20093,Apatinib,HS-20089,Platinum,Bevacizumab,nab-paclitaxel,Docetaxel, Irinotecan) The subsequent dose expansion study will select appropriate target populations (7 cohorts of recurrent ovarian cancer, HER2-negative advanced breast cancer, TNBC, advanced prostate cancer , advanced gastric cancer and HRD positive advanced ovarian cancer, fallopian tube cancer or primary peritoneal cancer) based on the data obtained in the phase Ia study, and determine the recommended phase II dose (RP2D) for each target population.

Safety evaluation will be performed for all the subjects in each cycle of therapy (3 weeks or 2 weeks) until Cycle 16, and then once every 6 weeks, until 30 days or 90 days after the last dose. The PK characteristics of HS-10502 will be evaluated during screening period and study treatment. Efficacy evaluation will be performed once every 6 weeks after C1D1 until objective disease progression or withdrawal from the study. As the disease progresses, survival follow-up will be performed every 12 weeks from the last dose.

Вмешательства

• Препарат HS-10502 + NHA
  HS-10502 + NHA
• Препарат HS-10502 + HS-20093
  HS-10502 + HS-20093
• Препарат HS-10502+ Apatinib
  HS-10502+ Apatinib
• Препарат HS-10502 + HS-20089
  HS-10502 + HS-20089
• Препарат HS-10502 + Platinum + Bevacizumab
  HS-10502 + Platinum + Bevacizumab
• Препарат HS-10502 + nab-paclitaxel or Docetaxel or Irinotecan
  HS-10502 + nab-paclitaxel or Docetaxel or Irinotecan
• Препарат HS-10502 + Bevacizumab
  HS-10502 + Bevacizumab

Первичные конечные точки

• Maximum tolerated dose (MTD) of HS-10502（Stage 1：Dose escalating stage） [Срок оценки: Cycle 1 (21 days)]
• Maximum applicable dose (MAD) of HS-10502（Stage 1：Dose escalating stage） [Срок оценки: Cycle 1 (21days)]
• Efficacy of HS-10502: Objective response rate (ORR)（Stage 2： Dose expansion stage） [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)

• Incidence and severity of treatment-emergent adverse events [Срок оценки: From Cycle 1 Day 1 (C1D1) until 21 days after the final dose. A cycle is 21days.]
• PK parameters: The maximum observed concentration (Cmax) of HS-10502 [Срок оценки: Cycle 1 Day 1 (each cycle is 21 days)]
• PK parameters: time to Cmax (Tmax) of HS-10502 [Срок оценки: Cycle 1 Day 1 (each cycle is 21 days)]
• 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 21 days)]
• PK parameters: Maximum plasma concentration at steady state (Css, max) of HS-10502 [Срок оценки: Cycle 2 Day 1 (each cycle is 21 days)]
• PK parameters: time to Css, max (Tss, max) of HS-10502 [Срок оценки: Cycle 2 Day 1 (each cycle is 21 days)]
• PK parameters: Minimum plasma concentration at steady state (Css, min) of HS-10502 [Срок оценки: Cycle 2 Day 1 (each cycle is 21 days)]
• 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 21days)]
• 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]
• 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]
• 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]
• 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 years or older (≥18 years).
• Patients diagnosed with pathologically confirmed advanced solid tumors.
• Subjects have at least one target lesion as assessed per the RECIST 1.1.
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 to 1 and no deterioration within 2 weeks before the first dose.
• Have a life expectancy of at least 12 weeks.
• Female subjects of childbearing potential are willing to take appropriate contraceptive measures and should not breastfeed from signing the informed consent until 6 months after the last dose; male subjects must agree to use barrier contraception (i.e. condoms) from signing the informed consent to 6 months after the last dose.
• Female subjects must have a negative pregnancy test within 7 days prior to the first dose (for subjects with tumor related abnormal elevation of human chorionic gonadotropin \[HCG\], an ultrasound of uterus and appendages should be performed within 7 days prior to the first dose to rule out pregnancy), or demonstrate no risk for pregnancy.
• Subject must be voluntarily enrolled in this clinical trial, be able to understand the study procedures and to sign written informed consent.

Критерии исключения

• Have received or is currently receiving the following treatment: PARPi/B7-H4/B7-H3-targeted therapies;
• Have received or is currently receiving the following treatment: PARPi/B7-H4/B7-H3-targeted therapies;
• Have received any of cytotoxic chemotherapy drugs, investigational drugs, anti-tumor traditional Chinese medicines or other anti-tumor drugs within 14 days prior to the first dose of study drug; or need to continue these drugs during the study.
• Presence of Grade ≥ 2 toxicities as per Common Terminology Criteria for Adverse Events due to prior anti-tumor therapy.
• Presence of pleural/abdominal effusion requiring clinical intervention.
• Known history of other primary malignancy.
• Evidence of brain metastasis and/or cancerous meningitis
• Inadequate bone marrow reserve or hepatic/renal functions.
• Cardiological examination abnormality.
• Severe, uncontrolled or active cardiovascular disorders.
• Serious or poorly controlled diabetes.
• Serious or poorly controlled hypertension.
• Clinically significant bleeding symptoms or significant bleeding tendency within 1 month prior to the first dose of study treatment.
• Serious infections within 4 weeks prior to the first dose.
• Have received systemic glucocorticoid therapy for more than 7 days within 28 days prior to the first dose study treatment, or require chronic (≥ 7 days) use of systemic glucocorticoids during the study, or have other acquired, congenital immunodeficiency disorders, or a history of organ transplantation.
• Presence of active infectious diseases such as hepatitis B, hepatitis C, tuberculosis, syphilis, or human immunodeficiency virus infection, etc.
• Current hepatic encephalopathy, hepatorenal syndrome, or Child-Pugh Class B or more severe cirrhosis.
• Any moderate or severe lung diseases that may interfere with the detection and treatment of drug-related pulmonary toxicity or may seriously affect respiratory function.
• History of severe neurological or psychiatric disorder.
• Pregnant or breast-feeding women or women who intend to become pregnant during the study.
• Attenuated live vaccination within 4 weeks prior to the first dose.
• Subjects with autoimmune disease that is active or is likely to recur.
• Subjects with gastrointestinal fistula, visceral fistula, gastrointestinal perforation, or abdominal abscess, or with symptoms/signs of intestinal obstruction within 6 months prior to the first dose of study drug.
• Subjects unlikely to comply with study procedures, restrictions and requirement as determined by the investigator.
• Subjects 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

Нерандомизированное

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Fudan University Shanghai Cancer Center — Шанхай

Идентификаторы

NCT: NCT06769425 · HS-10502-103

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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