A Study of YL201 in Patients With Advanced Solid Tumors

Официальное название

A Phase 1A/1B, Multicenter, Nonrandomized, Open-Label, First-in-Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of YL201 as a Single Agent and in Combination With Other Anti-Cancer Therapies in Patients With Advanced Solid Tumors

Обзор

This is a phase 1, multicenter, nonrandomized, open-label, first-in-human study of YL201 conducted in China and the United States. The study will include 2 parts: a dose escalation part (Part 1) followed by a dose expansion part (Part 2). Part 1 will estimate the MTD/RED(s) in dose escalation cohorts of patients with advanced solid tumors unresponsive to currently available therapies or for whom no standard therapy is available. Part 2 will include patients with selected advanced solid tumor types enrolled at the MTD/RED(s), to better define the safety profile and evaluate the efficacy of YL201.

Вмешательства

• Препарат YL201
  Patients will be treated with YL201 intravenous (IV) infusion once every 3 weeks (Q3W) as a cycle.
• Препарат YL201
  Patients will be treated with YL201 intravenous (IV) (A mg/kg or B g/kg infusion once every 3 weeks (Q3W) as a cycle.
• Препарат YL201 and atezolizumab
  Patients will be treated with YL201 intravenous (IV) infusion (A mg/kg or B mg/kg, up to 200mg) followed by atezolizumab on day 1 of each 21 day cycle

Первичные конечные точки

• Evaluate the occurrence of DLTs during the first cycle in Part 1 [Срок оценки: 21 days of Cycle 1]
• Evaluate the AEs in Part 2 as characterized by type, frequency, severity, timing, seriousness and relationship to study treatment [Срок оценки: By the global end of trial date, approximately within 36 months]
• Evaluate the prostate-specific antigen (PSA) response rate for patients with prostate cancer in Part 2 [Срок оценки: Approximately within 36 months]
• Evaluate the objective response rate (ORR) for patients with solid tumors other than prostate cancer in Part 2, assessed using RECIST version 1.1 [Срок оценки: Approximately within 36 months]
• Laboratory abnormalities as characterized by type, frequency, severity, and timing in Part 2 [Срок оценки: Biy the end of trial date, approximately within 36 months]
• Incidence, nature, and severity of AEs graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) V5.0 in Part 3 [Срок оценки: Biy the end of trial date, approximately within 36 months]
• Nature and frequency of dose-limiting toxicities (DLTs), incidence, nature, and severity of laboratory abnormalities in Part 3 [Срок оценки: At the end of cycle 1 (each cycle is 21 days)]

Вторичные конечные точки (12)

• Evaluate the AEs in Part 1 as characterized by type, frequency, severity, timing, seriousness and relationship to study treatment [Срок оценки: By the global end of trial date, approximately within 36 months]
• 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 CL [Срок оценки: Approximately within 36 months]
• Characterize the PK parameter Vd [Срок оценки: Approximately within 36 months]
• Characterize the PK parameter t1/2 [Срок оценки: Approximately within 36 months]
• Assess the incidence of anti-YL201 antibodies [Срок оценки: Approximately within 36 months]
• Evaluate the prostate-specific antigen (PSA) response rate for patients with prostate cancer in Part 1 [Срок оценки: Approximately within 36 months]
• Evaluate the PSA progression-free survival (PSA-PFS) for patients with prostate cancer [Срок оценки: Approximately within 36 months]
• Evaluate the radiological PFS (rPFS) for patients with prostate cancer [Срок оценки: Approximately within 36 months]
• Evaluate the failure-free survival (FFS) for patients with prostate cancer [Срок оценки: Approximately within 36 months]

Критерии участия

Критерии включения

• Informed of the trial before the start of the trial and voluntarily sign their name and date on the ICF
• Aged ≥18 years
• Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1
• Adequate organ and bone marrow function
• Female patients of childbearing potential must agree to use a highly effective form of contraception and not donate, or retrieve for their own use, ova from the time of screening and throughout the study period, and for at least 5 months after the last dose of atezolizumab or 6 months after the last dose of YL201, whichever is later. Male patients must agree to use a highly effective form of contraception and not freeze or donate sperm from the time of screening and throughout the study period, and for at least 6 months after the last dose of YL201.
• Life expectancy of ≥3 months
• Able and willing to comply with protocol visits and procedures
• Have at least 1 evaluable tumor lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
• Pathologically confirmed diagnosis of an advanced solid tumor (SCLC, mCRPC, ESCC and NSCLC are preferred) for which standard treatment had proven to be ineffective or intolerable, or no standard treatment is available. For ES-SCLC patients in Arm C: no prior anti-cancer treatment

Критерии исключения

• Concurrent enrollment in another clinical study, unless it is an observational (noninterventional) clinical study or during the follow-up period of an interventional study
• Prior systemic anticancer treatment including chemotherapy, molecular -targeted therapy, hormonal therapy, immunotherapy, or biological therapy within 3 weeks before the first dose of study drug (use of oral fluorouracil \[eg, tegafur and capecitabine\] or small molecular-targeted therapy within 2 weeks or 5 half-life periods \[whichever is shorter\]before the first dose; use of mitomycin or nitrosoureas within 6 weeks before the first dose; use of herbal medicine with antitumor indications or nonspecific immunomodulators \[eg, thymosin, interferon, and interleukin\] within 2 weeks before the first dose).
• Prior radiation therapy, including palliative stereotactic radiation with abdominal, within 4 weeks before the first dose of study drug (if palliative stereotactic radiation therapy without abdominal, within 2 weeks)
• Undergone major surgery (not including diagnostic surgery) within 4 weeks before the first dose of study drug or expect major surgery during the study
• Undergone allogeneic hematopoietic stem cell transplantation (HSCT) before the first dose of study drug, or autologous HSCT within 3 months before the first dose of study drug
• Received systemic steroids (>10 mg/day of prednisone or its equivalent) or other immunosuppressive therapy within 2 weeks before the first dose of study drug. Received any live vaccine within 4 weeks before the first dose of study drug or intend to receive a live vaccine during the study
• Known human immunodeficiency virus (HIV) infection
• Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Active HBV is defined as hepatitis B core antibody (HBcAb) or hepatitis B surface antigen (HBsAg) positive, and HBV DNA level above ULN at the study site; active HCV is defined as positive hepatitis C antibody and HCV RNA level above ULN at the study site
• Unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia and pigmentation) not yet resolved to NCI CTCAE Grade ≤1, baseline, or the level specified in the inclusion/exclusion criteria. Patients with chronic Grade 2 toxicities who are asymptomatic or adequately managed with stable medication may be enrolled after discussion with the sponsor
• A history of severe hypersensitivity reactions to the drug substances, inactive ingredients in the drug product, or other mAbs
• Women who are breastfeeding or pregnant as confirmed by pregnancy tests performed within 7 days before the first dose

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

США · 19 центров

• 002 — Fair Oaks
• 001 — La Jolla
• 003 — Lone Tree
• 004 — Washington D.C.
• 005 — Boston
• 006 — Ann Arbor
• 007 — Detroit
• 008 — St Louis
• … и ещё 11 центров

Испания · 10 центров

• 034 — Barcelona
• 035 — Barcelona
• 039 — Leganés
• 037 — Madrid
• 036 — Madrid
• 038 — Moncloa-Aravaca
• 041 — Pozuelo de Alarcón
• 042 — Usera
• … и ещё 2 центра

Франция · 8 центров

• 026 — Bordeaux
• 027 — Dijon
• 028 — Marseille
• 029 — Nantes
• 030 — Paris
• 031 — Poitiers
• 032 — Saint-Herblain
• 033 — Suresnes

Канада · 4 центра

• 020 — Edmonton
• 021 — Kelowna
• 022 — Brampton
• 023 — Toronto

Китай · 2 центра

• 024 — Гуанчжоу
• 025 — Чжэнчжоу

Польша · 2 центра

• 044 — Otwock
• 045 — Poznan

Публикации

• Ma Y, Yang Y, Huang Y, Fang W, Xue J, Meng X, Fan Y, Fu S, Wu L, Zheng Y, Liu J, Liu Z, Zhuang W, Rosen S, Qu S, Li B, Li M, Zhao Y, Yang S, Ji Y, Sommerhalder D, Luo S, Yang K, Li J, Lv D, Zhang P, Zhao Y, Hong S, Zhang Y, Zhao S, Chin S, Zhang X, Lian W, Cai J, Xue T, Zhang L, Zhao H. A B7H3-targeting antibody-drug conjugate in advanced solid tumors: a phase 1/1b trial. Nat Med. 2025 Jun;31(6):1 PMID 40082695

Идентификаторы

NCT: NCT05434234 · YL201-INT-101-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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