A Clinical Study of YL205 in Patients With Advanced Solid Tumors

Официальное название

A Multi-center, Open-label, Phase I/II Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetic Characteristics and Preliminary Efficacy of YL205 in Patients With Advanced Solid Tumors

Обзор

This study is a multicenter, open-label, phase I/II study of YL205 in China to evaluate the safety, tolerability, PK characteristics and preliminary efficacy of YL205 in the following selected patients with advanced solid tumors.

Вмешательства

• Препарат intravenous (IV) infusion
  YL205 is provided in the form of lyophilized powder under a strength of 160 mg/vial. Each vial should be reconstituted to 20 mg/mL. Prior to IV infusionSubjects will be treated with YL205 via intravenous (IV) infusion, once every 3 weeks (Q3W) as a treatment cycle

Первичные конечные точки

• To evalue the DLTs [Срок оценки: Approximately within 36 months]
• To evalue the TEAEs [Срок оценки: Approximately within 36 months]
• To evalue the TRAEs [Срок оценки: Approximately within 36 months]
• To evalue the serious adverse events (SAEs) [Срок оценки: Approximately within 36 months]
• Determination of the MTD of YL205 in the pivotal clinical study [Срок оценки: Approximately within 36 months]
• Determination of the RED of YL205 in the pivotal clinical study [Срок оценки: Approximately within 36 months]
• Determination of the RP2D of YL205 in the pivotal clinical study [Срок оценки: Approximately within 36 months]
• Assessed ORR (the proportion of CR and PR) by the investigator per RECIST v1.1 [Срок оценки: Approximately within 36 months]

Вторичные конечные точки (12)

• Characterize the PK parameter AUC [Срок оценки: Approximately within 36 months]
• Characterize the PK parameter Cmax [Срок оценки: Approximately within 36 months]
• Characterize the PK parameter Ctrough [Срок оценки: Approximately within 36 months]
• Characterize the PK parameter Vd [Срок оценки: Approximately within 36 months]
• Characterize the PK parameter CL [Срок оценки: Approximately within 36 months]
• Characterize the PK parameter Tmax [Срок оценки: Approximately within 36 months]
• Characterize the PK parameter t1/2 [Срок оценки: Approximately within 36 months]
• Assessed the disease control rate (DCR) per RECIST v1.1 [Срок оценки: Approximately within 36 months]
• Assessed the duration of response (DOR) per RECIST v1.1 [Срок оценки: Approximately within 36 months]
• Assessed the time to response (TTR) per RECIST v1.1 [Срок оценки: Approximately within 36 months]
• Assessed the progression free survival (PFS) per RECIST v1.1 [Срок оценки: Approximately within 36 months]
• Assessed the depth of response (DpR) per RECIST v1.1 [Срок оценки: Approximately within 36 months]

Критерии участия

Критерии включения

• 1\) Subjects who are informed of relevant information of the study prior to initiation of the study and voluntarily sign and date on the informed consent form (ICF).

2\) Age ≥18 years. 3) Be willing to follow and be able to complete all the study procedures. 4) Body mass index (BMI) within the range of 18 to 32 kg/m2, and body weight ≥45kg for female subjects.

5） Patients with histologically or cytologically confirmed locally advanced or metastatic ovarian cancer (OC), non-squamous non-small cell lung cancer (NSQ NSCLC), renal cell carcinoma (RCC), endometrial cancer (EC), or other Napi2b-overexpressing tumors。 6) Patients with positive Napi2b test results at the central laboratory. 9) At least one radiologically evaluable lesion for subjects in Part 1; At least one measurable extracranial lesion (non-radiation fields) for subjects in Part 2 and Part 3.

10\) Expected survival ≥3 months. 11) Female subjects of childbearing potential must agree to take effective contraceptive measures and must not undergo egg donation or egg retrieval for their own use from screening throughout the study period and for at least 6 months after the last dose of the investigational drug. Male subjects must agree to take effective contraceptive measures and must not undergo sperm cryopreservation or sperm donation from screening throughout the study period and for at least 6 months after the last dose of the investigational drug.

12\) subjects must provide tumor samples. 13) Subjects who are capable of and willing to comply with the visits and procedures stipulated in the study protocol.

Критерии исключения

• 1\) Subjects with a treatment history with drugs targeting Napi2b. 2) Subjects with a history of intolerance to topoisomerase I inhibitors or ADC therapy.

3\) Subjects who are participating in another clinical study, with the exception an of observational (non-interventional) clinical study or the follow-up period of an interventional study.

4\) Subjects with an insufficient washout period from the previous anti-tumor therapy to the first dose.

5\) Subjects who received radiotherapy, including palliative stereotactic radiotherapy on the abdomen, within 4 weeks prior to the first dose.

6\) Subjects who received major surgery within 4 weeks prior to the first dose or those who plan to receive major surgery during the study.

7\) Subjects who received allogeneic bone marrow transplantation or solid organ transplantation.

8\) Subjects who received systemic steroids or other immunosuppressive treatment within 2 weeks prior to the first dose of the investigational drug.

9\) Subjects who received any live vaccine within 4 weeks prior to the first dose or those who plan to receive live vaccines during the study.

10\) Subjects with a medical history of leptomeningeal carcinoma or cancerous meningitis.

11\) Subjects with brain metastasis or spinal cord compression. 12) Subjects with uncontrolled or clinically significant cardiovascular and cerebrovascular diseases.

13\) Subjects who were diagnosed with Gilbert's syndrome. 14) Subjects with significantly symptomatic or unstable effusion in the third space requiring repeated drainage.

15\) Subjects with medical history of gastrointestinal perforation and/or fistula within 6 months prior to the first dose, or active gastric ulcers, duodenal ulcer, colitis ulcerative, or other gastrointestinal disorders that may cause hemorrhage or perforation in the opinion of the investigator.

16\) Subjects with serious infection (Grade ≥3 as per NCI CTCAE v5.0) prior to the first dose.

17\) Subjects with human immunodeficiency virus (HIV), active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection; subjects with positive syphilis antibody and a positive titer result.

18\) Subjects with unresolved toxicity caused by previous anti-tumor therapy. 20) Subjects with a history of serious allergic reactions to drugs, inactive ingredients in drug products, or other monoclonal antibodies.

21\) Female subjects who are pregnant as confirmed by a pregnancy test within 3 days prior to the first dose, or lactating women.

22\) Subjects who have any diseases, medical conditions, organ system dysfunction, or social conditions.

23\) Subjects with multiple primary malignancies within 5 years prior to the signing of the ICF, except for fully resected non-melanoma skin cancer, radically treated carcinoma in situ, or other radically treated solid tumors.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 32 центра

• Fujian Provincial Cancer Hospital — Фучжоу
• Sun Yat-Sen Memorial Hospital,Sun Yat-Sen University — Гуанчжоу
• Guangxi Medical University Cancer Hospital — Nanning
• Hainan General Hospital — Haikou
• The Fourth Hospital of Hebei Medical University — Shijiazhuang
• Harbin Medical University Cancer Hospital — Харбин
• Anyang Cancer Hospital — Anyang
• Henan Cancer Hospital — Чжэнчжоу
• … и ещё 24 центра

США · 11 центров

• Sarah Cannon Research Institute (SCRI)- Denver — Denver
• Yale Cancer Center — New Haven
• Florida Cancer Specialists - Lake Mary — Lake Mary
• Norton Cancer Institute — Louisville
• Washington University School of Medicine - Center for advanced Medicine — St Louis
• Comprehensive Cancer Centers of Nevada (CCCN) - Central Valley — Las Vegas
• Southwest Women's Oncology — Albuquerque
• Stephenson Cancer Center (Oklahoma) — Oklahoma City
• … и ещё 3 центра

Идентификаторы

NCT: NCT06459973 · YL205-CN-101-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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