A Phase I, First in Human Study of CBA-1205, Anti-DLK1 Monoclonal Antibody in Patients With Advanced Solid Tumors, Hepatocellular Carcinoma (HCC), Melanoma, and Pediatric Cancer

Официальное название

A Phase I, First in Human Study of CBA-1205, Anti-DLK1 Monoclonal Antibody in Patients With Advanced Solid Tumors.

Обзор

In this first-in-human, muticenter, non-randomized, open-label, standard 3+3 dose escalation Phase I study encompasses 5 parts (Part 1-5). The purpose of this FIH study is to evaluate the safety and tolerability profile of CBA-1205.

Подробное описание

To evaluate safety and efficacy of CBA-1205 in the following five parts in a stepwise manner:

Part 1

* In Part 1, safety and tolerability in patients with Solid Tumor where no standard treatment is available, or who are intolerable or non-responder to the standard treatment will be evaluated. Initial dose for Part 2 will be determined.

Part 2

* In Part 2, safety and tolerability in patients with advanced and/or recurrent Hepatocellular Carcinoma which are unresectable, or who are intolerable or non-responder to the standard treatment will be evaluated. Recommended dose in this population will be determined.

Part 3

* In Part 3, safety and efficacy at the recommended dose in patients with advanced and/or recurrent Hepatocellular Carcinoma which are unresectable, or who are intolerable or non-responder to the standard treatment will be evaluated.

Part 4

* In Part 4, safety and efficacy in patients with Malignant Melanoma who are refractory or intolerant to standard therapy.

Part 5

* In Part 5, safety, tolerability and the recommended dose of the study drug in patients with Pediatric Cancer where no standard treatment is available, or who are intolerable or non-responder to the standard treatment will be evaluated.

PK analysis

Вмешательства

• Препарат CBA-1205 Part 1
  CBA-1205: 0.1, 0.3, 1, 3, 10, 20, 30 mg/kg (Intravenous solution)
• Препарат CBA-1205 Part 2
  CBA-1205: 20 mg/kg and 30 mg/kg (Intravenous solution)
• Препарат CBA-1205 Part 3
  CBA-1205: 30 mg/kg (Intravenous solution)
• Препарат CBA-1205 Part 4
  CBA-1205: 20 mg/kg (Intravenous solution)
• Препарат CBA-1205 Part 5
  CBA-1205: 10 mg/kg (The initial cohort, Intravenous solution)

Первичные конечные точки

• Dose limiting toxicity [Срок оценки: Part 1, 2 and 5 - Dose limiting toxicity : For 28 days after the first dose of study treatment]
• Adverse Event [Срок оценки: Adverse event : Maximum 12 months]

Вторичные конечные точки (3)

• Serum CBA-1205 concentration [Срок оценки: From Day 1 to Day 43 (or until Discontiuation of treatment)]
• Immunogenicity [Срок оценки: From Day1 to Day 43 (or until Discontiuation of treatment)]
• Efficacy [Срок оценки: Screening, Day 1 of Cycle 2 and 3, and Day 1 of even-numbered cycles from Cycle 4 onward until treatment discontinuation. Maximum 12 months]

Критерии участия

Inclusion Criteria:(Part 1-4)

• Patients who provide voluntary written informed consent to participate in the study
• Patients with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of≤1
• Patients with preserved renal function as evidenced by laboratory data obtained within 7 days before enrollment (creatinine: ≤ ULN ×1.5)
• Patients who meet the following laboratory criteria of bone marrow function as evidenced by laboratory data obtained within 7 days before enrollment: Neutrophil count;≥1500/μL, Platelet count; ≥75000/μL, Hemoglobin;≥9.0 g/dL.
• Patients having Solid Tumors with no standard therapy available or refractory or intolerable to standard therapy (Part2, 3)
• Patients with Child-Pugh A or B (Part2, 3)
• Patients with Malignant Melanoma who are refractory or intolerant to standard therapy (Part 4)

Inclusion Criteria:(Part 5)

• Patients who provide voluntary written informed consent to participate in the study from both the subject (if aged 16 years or older) and their legal representatives
• Japanese patients aged 2 years or older and under 20 years at the time of informed consent
• Patients with a Lansky Performance Status (LPS) of ≥70 (for patients aged 15 years or younger) or a Karnofsky Performance Status (KPS) of ≥70 (for patients aged 16 years or older)
• Patients with preserved renal function as evidenced by laboratory data obtained within 7 days before enrollment (eGFR ≥60 mL/min/1.73 m²)
• Pediatric patients with cancers with no standard therapy available or refractory or intolerable to the standard therapy

Exclusion criteria: (Part1-5)

• Patients who have undergone major surgery within 28 days before enrollment
• Patients who have received anticancer treatment with surgical therapy, radiation therapy, and/or drug therapy within 14 days before enrollment
• Patients who have received anticancer treatment with immune checkpoint inhibitor, etc. within 28 days before enrollment
• Patients with Grade 2 or higher concurrent disease or prior therapy-related toxicity
• Patients who have received any other investigational product within 28 days before enrollment
• Patients with current or previous inadequately controlled or clinically significant cardiac disease
• Patients who, in the opinion of the investigator or subinvestigator, is not appropriate

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

Простое слепое

Основная цель

Лечение

Центры проведения

Япония · 5 центров

• National Cancer Center Hospital East — Kashiwa
• Kanagawa Cancer Center — Yokohama
• Niigata University Medical and Dental Hospital — Niigata
• National Cancer Center Hospital — Chūō
• University of Yamanashi Hospital — Chūō

Публикации

• Nakamura K, Takahashi K, Sakaguchi I, Satoh T, Zhang L, Yanai H, Tsukumo Y. A Novel Glycoengineered Humanized Antibody Targeting DLK1 Exhibits Potent Anti-Tumor Activity in DLK1-Expressing Liver Cancer Cell Xenograft Models. Int J Mol Sci. 2024 Dec 19;25(24):13627. doi: 10.3390/ijms252413627. PMID 39769389
• Katsuya Y, Ikeda M, Koyama T, Sato J, Okada M, Matsubara N, Kondoh C, Mukohara T, Watanabe K, Kotani D, Ogawa Y, Taoka S, Yamamoto N. A Phase I, First-In-Human Study of CBA-1205, an Anti-DLK1 Monoclonal Antibody, in Patients With Advanced Solid Tumors. Cancer Sci. 2025 Apr;116(4):1012-1022. doi: 10.1111/cas.16454. Epub 2025 Jan 20. PMID 39832211

Идентификаторы

NCT: NCT06636435 · 1205-001 · jRCT2080225288

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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