Phase 1a/1b First-in-Human Study of BG-C9074 Alone and in Combination With Other Anticancer Therapies in Patients With Advanced Solid Tumors

Официальное название

Phase 1a/1b Study of BG-C9074, an Antibody Drug Conjugate Targeting B7H4, as Monotherapy and in Combination With Other Anticancer Therapies in Patients With Advanced Solid Tumors

Обзор

This is a first-in-human, dose finding and dose expansion study to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary antitumor activity of BG-C9074 alone and in combination with other anticancer therapies in patients with advanced solid tumors.

Вмешательства

• Препарат BG-C9074
  administered by intravenous infusion
• Препарат Tislelizumab
  administered by intravenous infusion
• Препарат Bevacizumab
  administered by intravenous infusion

Первичные конечные точки

• Phase 1a: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) [Срок оценки: Approximately 3 years]
• Phase 1a: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of BG-C9074 [Срок оценки: Approximately 18 months]
• Phase 1a: Recommended Dose for Expansion (RDFE) of BG-C9074. [Срок оценки: Approximately 18 months]
• Phase 1b: Overall Response Rate (ORR) as monotherapy and in combination with tislelizumab [Срок оценки: Approximately 3 years]
• Phase 1b: Recommended Phase 2 dose (RP2D) of BG-C9074 as monotherapy and in combination with bevacizumab or tislelizumab [Срок оценки: Approximately 30 months]

Вторичные конечные точки (12)

• Phase 1a: ORR as monotherapy and in combination with tislelizumab [Срок оценки: Approximately 3 years]
• Phase 1b: ORR as monotherapy and in combination with bevacizumab or tislelizumab [Срок оценки: Approximately 3 years]
• Phase 1b: ORR per B7-H4 (B7 homolog 4) protein expression [Срок оценки: Approximately 3 years]
• Duration of Response (DOR) [Срок оценки: Approximately 3 years]
• Duration of Response (DOR) per B7-H4 protein expression [Срок оценки: Approximately 3 years]
• Disease Control Rate (DCR) [Срок оценки: Approximately 3 years]
• Disease Control Rate (DCR) per B7-H4 protein expression [Срок оценки: Approximately 3 years]
• Clinical Benefit Rate (CBR) [Срок оценки: Approximately 3 years]
• Clinical Benefit Rate (CBR) per B7-H4 protein expression [Срок оценки: Approximately 3 years]
• Phase 1b: Progression Free Survival (PFS) [Срок оценки: Approximately 3 years]
• Phase 1b: Number of Participants with AEs and SAEs [Срок оценки: Approximately 3 years]
• Maximum observed plasma concentration (Cmax) for BG-C9074 [Срок оценки: Twice in the first four months]

Критерии участия

Критерии включения

• Able to provide a signed and dated written informed consent prior to any study-specific procedures, sampling, or data collection.
• Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1.
• Participants with selected histologically or cytologically confirmed advanced, metastatic, and unresectable solid tumors who have previously received standard systemic therapy and whose cancer is not amenable to therapy with curative intent, and for whom further treatment is not available or not tolerated. Enrollment will be limited to participants with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer, cholangiocarcinoma (CCA), endometrial cancer, squamous non-small cell lung cancer (NSCLC), triple-negative breast cancer (TNBC), or ovarian cancer. Enrollment in the Japan cohort will be limited to participants with HR+/HER2- breast cancer, TNBC, endometrial cancer, or ovarian cancer.
• ≥ 1 measurable lesion per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1)
• Able to provide an archived tumor tissue sample.
• Adequate bone marrow and organ function.
• Females of childbearing potential must be willing to use a highly effective method of birth control for the duration of the study, and for ≥ 7 months after the last dose of study drug(s).
• Nonsterile males must be willing to use a highly effective method of birth control for the duration of the study treatment period and for ≥ 4 months after the last dose of study drug(s).

Критерии исключения

• Prior treatment with a B7 homolog 4 (B7H4)-targeting antibody-drug conjugate (ADC) or an ADC with a topoisomerase 1 inhibitor (TOP1i) payload.
• Active leptomeningeal disease or uncontrolled, untreated brain metastasis
• Any malignancy ≤ 2 years before the first dose of study treatment(s) except for the specific cancer under investigation in this study and any locally recurring cancer that has been treated with curative intent (eg, resected basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix or breast).
• History of interstitial lung disease, ≥ Grade 2 noninfectious pneumonitis, oxygen saturation at rest < 92%, or requirement for supplemental oxygen (including intermittent use) at baseline.
• Uncontrolled diabetes.
• Infection (including tuberculosis infection) requiring systemic (oral or intravenous) antibacterial, antifungal, or antiviral therapy ≤ 14 days before the first dose of study treatment(s).

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 15 центров

• Cancer Hospital Chinese Academy of Medical Sciences — Пекин
• Fujian Cancer Hospital — Фучжоу
• Sun Yat Sen University Cancer Center — Гуанчжоу
• Harbin Medical University Cancer Hospital — Харбин
• Union Hospital of Tongji Medical College, Huazhong University of Science and Technology — Ухань
• Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology — Ухань
• The Second Hospital of Dalian Medical University — Dalian
• Shengjing Hospital of China Medical University — Шэньян
• … и ещё 7 центров

Австралия · 8 центров

• Blacktown Cancer and Haematology Centre — Blacktown
• Macquarie University — North Ryde
• Cancer Care Wollongong — Wollongong
• Princess Alexandra Hospital — Woolloongabba
• Monash Health — Clayton
• Cabrini Hospital Malvern — Malvern
• Peter Maccallum Cancer Centre — Melbourne
• Linear Clinical Research — Nedlands

Бразилия · 7 центров

• Hospital Sirio Libanes Brasilia — Brasília
• Liga Norte Riograndene Contra O Cancer — Natal
• Hospital Sao Lucas Da Pucrs — Porto Alegre
• Instituto Nacional de Cancer Hospital Do Cancer Ii — Rio de Janerio
• Fundacao Faculdade Regional de Medicina de Sao Jose Do Rio Preto — São José do Rio Preto
• Icesp Instituto Do Cancer Do Estado de Sao Paulo Octavio Frias de Oliveira — São Paulo
• Clinica de Pesquisa E Centro de Estudos Em Oncologia Ginecologica E Mamaria — São Paulo

США · 5 центров

• Usc Norris Comprehensive Cancer Center (Nccc) — Los Angeles
• University of Colorado Cancer Center — Aurora
• Florida Cancer Specialist Research Institute Lake Nona — Orlando
• Sidney Kimmel Comprehensive Cancer At Johns Hopkins — Baltimore
• James Cancer Hospital and Solove Research Institute — Columbus

Япония · 2 центра

• National Cancer Center Hospital East — Kashiwa
• Cancer Institute Hospital of Jfcr — Kotoku

Идентификаторы

NCT: NCT06233942 · BG-C9074-101 · jRCT2031250755

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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