An Investigational Study of BGB-58067 As a Single Agent and in Combination With Anticancer Agents in Participants With Advanced Solid Tumors

Официальное название

A Phase 1a/b Study Investigating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Antitumor Activity of PRMT5 Inhibitor BGB-58067 Alone and in Combination With Anticancer Agents in Patients With Advanced Solid Tumors

Обзор

This is an open-label, multicenter, first-in-human dose escalation and dose expansion study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of BGB-58067 alone, in combination with BG-89894 (discontinued), and in combination with standard of care therapy in participants with advanced solid tumors and with methylthioadenosine phosphorylase (MTAP) deficiency.

Подробное описание

BGB-58067 is a new drug designed to target a specific protein called protein arginine methyltransferase 5 (PRMT5). This protein is involved in many cell activities and can promote cancer growth when it is overactive. High levels of PRMT5 are linked to poor outcomes in several types of cancer.

This new study will check how safe and helpful a potential anticancer drug called BGB-58067 is. This drug will be tested alone, in combination with BG-89894 (discontinued), and in combination with standard of care therapy in participants with advanced solid tumors and with MTAP deficiency.

Note: Our company, previously known as BeiGene, is now officially BeOne Medicines. Because some of our older studies were sponsored under the name BeiGene, you may see both names used for this study on this website.

Вмешательства

• Препарат BGB-58067
  Planned doses administered on specified days per protocol.
• Препарат BG-89894
  Planned doses administered on specified days per protocol.
• Препарат Standard of Care Therapy
  Administered in accordance with relevant local guidelines and/or prescribing information.

Первичные конечные точки

• Phase 1a: Number of Participants with Adverse Events and Serious Adverse Events [Срок оценки: From first dose of the study drug(s) to 30 days after the last dose or initiation of a new anticancer therapy, whichever occurs first (approximately 13 months)]
• Phase 1a: Number of Participants with Adverse Events that meet Dose-Limiting Toxicity (DLT) criteria [Срок оценки: Approximately 1 month]
• Phase 1a: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of BGB-58067 alone, in combination with BG-89894, and in combination with standard of care therapy [Срок оценки: Approximately 1 month]
• Phase 1a: Recommended Dose(s) for Expansion (RDFE[s]) of BGB-58067 alone, in combination with BG-89894, and in combination with standard of care therapy [Срок оценки: Approximately 13 months]
• Phase 1b: Recommended Phase 2 Dose (RP2D) of BGB-58067 alone and in combination with standard of care therapy [Срок оценки: Approximately 2 years]
• Phase 1b: Objective Response Rate (ORR) [Срок оценки: Approximately 2 years]

Вторичные конечные точки (12)

• Phase 1a: Objective Response Rate (ORR) [Срок оценки: Approximately 2 years]
• Phase 1a and 1b: Maximum observed plasma concentration (Cmax) of BGB-58067 [Срок оценки: Approximately 2 months]
• Phase 1a and 1b: Minimum observed plasma concentration (Cmin) of BGB-58067 [Срок оценки: Approximately 9 months]
• Phase 1a and 1b: Time to reach maximum observed plasma concentration (Tmax) of BGB-58067 [Срок оценки: Approximately 2 months]
• Phase 1a and 1b: Apparent oral clearance (CL/F) for BGB-58067 [Срок оценки: Approximately 2 months]
• Phase 1a and 1b: Half-life (t1/2) of BGB-58067 [Срок оценки: Approximately 2 months]
• Phase 1a and 1b: Area under the concentration-time curve (AUC) of BGB-58067 [Срок оценки: Approximately 2 months]
• Phase 1a and 1b: Apparent volume of distribution (Vz/F) for BGB-58067 [Срок оценки: Approximately 2 months]
• Phase 1a and 1b: Accumulation ratio (AR) for BGB-58067 [Срок оценки: Approximately 2 months]
• Phase 1a and 1b: Plasma concentrations of BGB-58067 [Срок оценки: Approximately 9 months]
• Phase 1a and 1b: Duration of Response (DOR) [Срок оценки: Approximately 2 years]
• Phase 1a and 1b: Disease Control Rate (DCR) [Срок оценки: Approximately 2 years]

Критерии участия

Критерии включения

• Participants must sign the ICF and be capable of giving written informed consent
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 or Karnofsky Performance Scale (KPS) ≥ 70
• Life expectancy ≥ 3 months
• Evidence of homozygous loss of MTAP or lost MTAP expression in the tumor tissue
• Able to provide tumor sample to meet the minimum tissue requirement for central MTAP deficiency testing
• Participants with histologically or cytologically confirmed advanced, metastatic, or unresectable solid tumors, whose diseases have progressed or recurred after receiving standard systemic therapy or radiotherapy, or for whom standard systemic therapy is not available or tolerated, or would be unlikely to tolerate or derive clinically meaningful benefit from appropriate standard treatment in the opinion of the investigator; participants with advanced, metastatic, or unresectable solid tumors who have not received prior systemic treatment or have received one cycle of standard-of-care therapies will be enrolled in selected cohorts
• Adequate organ function

Критерии исключения

• Prior treatment with any methylthioadenosine (MTA)-cooperative PRMT5 inhibitor or methionine adenosyltransferase 2a (MAT2A) inhibitor
• Active leptomeningeal disease or symptomatic spinal cord compression
• Uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent drainage
• Any malignancy ≤ 2 years before first dose of study drug except for the specific cancer under investigation in this study and any locally recurring cancer that has been treated curatively
• Significantly impaired pulmonary function
• Clinically significant infections
• Serologically active hepatitis B or C infection
• Known HIV infection. Participants with treated HIV infection may be included in Phase 1b if they meet certain criteria
• High cardiovascular risk factors
• QTcF > 470 ms based on the screening triplicate 12-lead ECG records and/or a history of additional risk factors for torsade de pointes (eg, heart failure, hypokalemia, or a family history of Long QT Syndrome)
• Toxicities (because of prior anticancer therapy) that have not recovered to baseline or stabilized
• Participants who are unable to swallow or with disease/procedure significantly affecting gastrointestinal function
• Female participants who are pregnant or are breastfeeding
• Concurrent participation in another therapeutic clinical study (participation in observational or noninterventional studies is allowed)

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

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 47 центров

• The Second Hospital of Anhui Medical University — Хэфэй
• Cancer Hospital Chinese Academy of Medical Sciences — Пекин
• Beijing Cancer Hospital — Пекин
• Peking Union Medical College Hospital — Пекин
• Beijing Chest Hospital, Capital Medical University — Пекин
• Chongqing University Cancer Hospital — Чунцин
• Fujian Cancer Hospital — Фучжоу
• The First Affiliated Hospital of Xiamen University — Xiamen
• … и ещё 39 центров

США · 11 центров

• Usc Norris Comprehensive Cancer Center (Nccc) — Los Angeles
• Adventhealth — Celebration
• Dana Farber Cancer Institute — Boston
• Washington University School of Medicine — St Louis
• Nyu Langone Health — New York
• Columbia University Medical Center — New York
• Sidney Kimmel Cancer Center — Philadelphia
• Tennessee Oncology, Pllc Nashville — Nashville
• … и ещё 3 центра

Бразилия · 8 центров

• Fundacao Pio Xii Hospital de Amor de Barretos — Barretos
• Fundacao Universidade de Caxias Do Sul — Caxias do Sul
• Centro Gaucho Integrado de Oncologia Hospital Mae de Deus — Porto Alegre
• Hospital Sao Lucas Da Pucrs — Porto Alegre
• Ensino E Terapia de Inovacao Clinica Amo Etica — Salvador
• Icesp Instituto Do Cancer Do Estado de Sao Paulo Octavio Frias de Oliveira — São Paulo
• Nucleo de Pesquisa E Ensino Da Rede Sao Camilo — São Paulo
• Sociedade Beneficente Israelita Brasileira Hospital Albert Einstein — São Paulo

South Korea · 6 центров

Список центров уточняется — проверьте первичный протокол.

Австралия · 5 центров

• Blacktown Cancer and Haematology Centre — Blacktown
• Princess Alexandra Hospital — Woolloongabba
• Monash Health — Clayton
• Austin Health — Heidelberg
• Linear Clinical Research — Nedlands

Франция · 5 центров

• Centre de Lutte Contre Le Cancer Institut Bergonie — Bordeaux
• Institut Paoli Calmettes — Marseille
• Institut Curie Paris — Paris
• Institut de Cancerologie de Louest — Saint-Herblain
• Institut Gustave Roussy — Villejuif

Малайзия · 5 центров

• Hospital Pulau Pinang — George Town
• Hospital Raja Perempuan Zainab Ii — Johor Bahru
• Hospital Kuala Lumpur — Kuala Lumpur
• … и ещё 2 центра

Таиланд · 5 центров

Список центров уточняется — проверьте первичный протокол.

Испания · 4 центра

Список центров уточняется — проверьте первичный протокол.

Дания · 1 центр

• Rigshospitalet — Copenhagen

Moldova · 1 центр

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT06589596 · BGB-58067-101 · 2024-515307-19-00 · CTR20244451

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)
• NMPA/CDE CTR20244451 (платформа chinadrugtrials.org.cn)

Открыть это исследование на ClinicalTrials.gov ↗