A First-in-human Study to Learn About the Safety of BAY 3547926 and How Well it Works in Participants With Advanced Liver Cancer

Официальное название

A Multicenter, Open Label, Non-randomized First-in-human Phase 1 Dose Escalation and Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Anti-tumor Activity of BAY 3547926 Alone, and in Combination, in Participants With Advanced Hepatocellular Carcinoma (HCC)

Обзор

In this study, researchers want to learn about the safety of a new drug, BAY 3547926, and how well the drug works in people with a type of liver cancer called advanced hepatocellular carcinoma (HCC), which has a special protein called Glypican 3 (GPC3). Researchers want to find the best dose of BAY 3547926 for people with advanced HCC and look at the way the body absorbs and distributes the drug. The study drug, BAY 3547926, delivers a radioactive agent to cancer cells. The radioactive agent emits radiations which can damage the cancer cells and cause them to die. These radiations travel a small distance, so are expected to cause little damage to surrounding healthy tissues. This is the first study of BAY 3547926 in humans. Participants will take part in one of the 4 different parts of the study. In Part 1, participants will receive different doses of BAY 3547926 alone to find the dose that is deemed safe and works best for the participants. When this dose has been found, a larger number of participants will receive BAY 3547926 alone in Part 2 or with other treatments in Parts 3 and 4 of the study. During the study, the doctors and their study team will do health check-ups, take pictures (scans) of the body, collect blood and urine samples, and ask participants questions about how they are feeling and what health problems they are having.

Вмешательства

• Препарат BAY 3547926
  antibody conjugate with actinium-225 label
• Препарат BAY 3547922
  antibody conjugate without actinium-225 label as preinjection
• Препарат BAY 3713391
  Radioactive imaging agent - optional preinjection
• Препарат BAY 3713389
  optional preinjection

Первичные конечные точки

• Part 1 (dose escalation): Occurrence and severity of TEAEs [Срок оценки: up to 60 months after first administration]
• Part 1 (dose escalation): Recommended safe and active dose (RSAD) [Срок оценки: up to 60 months after first administration]
• Part 2 (dose expansion): Occurrence and severity of TEAEs [Срок оценки: up to 60 months after first administration]
• Part 2 (dose expansion): ORR using RECIST 1.1 by investigator assessment [Срок оценки: up to 60 months after first administration]
• Part 2 (dose expansion): DCR using RECIST 1.1 by investigator assessment [Срок оценки: up to 60 months after first administration]
• Part 2 (dose expansion): DoR using RECIST 1.1 by investigator assessment [Срок оценки: up to 60 months after first administration]
• Part 2 (dose expansion): PFS using RECIST 1.1 by investigator assessment [Срок оценки: up to 60 months after first administration]
• Parts 3 and 4 (dose expansion in combination): Occurrence and severity of TEAEs [Срок оценки: up to 60 months after first administration]
• Parts 3 and 4 (dose expansion in combination): ORR using RECIST 1.1 by investigator assessment [Срок оценки: up to 60 months after first administration]
• Parts 3 and 4 (dose expansion in combination): DCR using RECIST 1.1 by investigator assessment [Срок оценки: up to 60 months after first administration]

Вторичные конечные точки (12)

• Part 1 (dose escalation): Recommended dose level(s) based on occurrence and severity of TEAEs and DLTs, PK, immunogenicity, and preliminary anit-tumor activity (ORR using RECIST 1.1 by Investigator assessment) [Срок оценки: up to 60 months after first administration]
• Part 1 (dose escalation): Recommended dosing regimen based on occurrence and severity of TEAEs and DLTs, PK, immunogenicity, and preliminary anti-tumor activity (ORR using RECIST 1.1 by Investigator assessment) [Срок оценки: up to 60 months after first administration]
• Part 1 (dose escalation): ORR using RECIST 1.1 by investigator assessment [Срок оценки: up to 60 months after first administration]
• Part 1 (dose escalation): DCR using RECIST 1.1 by investigator assessment [Срок оценки: up to 60 months after first administration]
• Part 1 (dose escalation): DoR using RECIST 1.1 by investigator assessment [Срок оценки: Up to 60 months after first administration]
• Part 1 (dose escalation): PFS using RECIST 1.1 by investigator assessment [Срок оценки: up to 60 months after first administration]
• Part 1 (dose escalation): Cmax of BAY 3547926 after a single dose and after multiple doses [Срок оценки: up to 36 weeks after first administration]
• Part 1 (dose escalation): AUC of BAY 3547926 after a single dose and after multiple doses [Срок оценки: up to 36 weeks after first administration]
• Part 1 (dose escalation): Clearance of BAY 3547926 after a single dose and after multiple doses if data allow [Срок оценки: up to 36 weeks after first administration]
• Part 2 (dose expansion): Recommended dose based on safety, PK, IG and markers of pharmacodynamic activity and efficacy assessments [Срок оценки: up to 36 months after first administration]
• Part 2 (dose expansion): Recommended schedule based on safety, PK, IG and markers of pharmacodynamic activity and efficacy assessments [Срок оценки: up to 36 months after first administration]
• Part 2 (dose expansion): Cmax of BAY 3547926 after a single dose and after multiple doses [Срок оценки: up to 36 weeks after first administration]

Критерии участия

Критерии включения

• Locally advanced or metastatic and/or unresectable HCC (hepatocellular carcinoma) with histological or cytological confirmation, or non-invasive diagnosis as per American Association for the Study of Liver Diseases (AASLD) criteria in participants with a confirmed diagnosis of cirrhosis.
• Demonstrated positive centrally confirmed GPC3 expression by immunohistochemistry (IHC) on tumor sample.
• Disease not amenable to, or progressive disease after, curative surgery and/or locoregional therapies of established efficacy such as resection, local ablation, chemoembolization.
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1.
• At least one measurable lesion by computed tomography (CT) scan or magnetic resonance imaging (MRI) according to Response Evaluation Criteria in Solid Tumours (RECIST) 1.1. as assessed by local site Investigator within 28 days prior to the start of the study treatment.
• Adequate bone marrow and organ function

Критерии исключения

• Fibrolamellar HCC, sarcomatoid HCC, and mixed hepatocellular/cholangiocarcinoma subtypes.
• Participants with a history or clinical evidence of CNS metastases, unless they meet specific criteria
• History of encephalopathy ≥ Grade 2 within the past 12 months
• Clinically significant ascites

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

Другое

Центры проведения

Канада · 4 центра

• Toronto — Toronto
• Montreal — Montreal
• Montreal — Montreal
• Sherbrooke — Sherbrooke

Великобритания · 4 центра

• London — London
• London — London
• Glasgow — Glasgow
• Sutton — Sutton

Бельгия · 3 центра

• Edegem — Edegem
• Leuven — Leuven
• Kortrijk — Kortrijk

Испания · 3 центра

• L'Hospitalet de Llobregat — L'Hospitalet de Llobregat
• Madrid — Madrid
• Pamplona — Pamplona

США · 2 центра

• Dothan — Dothan
• Duarte — Duarte

Финляндия · 2 центра

• Tampere — Tampere
• Turku — Turku

Китай · 1 центр

• Xuhui District — Xuhui

Франция · 1 центр

• Montpellier — Montpellier

Идентификаторы

NCT: NCT06764316 · 22262 · 2024-516615-25-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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