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

Official title

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

Overview

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.

Detailed description

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.

Interventions

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

Primary outcome measures

• Phase 1a: Number of Participants with Adverse Events and Serious Adverse Events [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: Approximately 13 months]
• Phase 1b: Recommended Phase 2 Dose (RP2D) of BGB-58067 alone and in combination with standard of care therapy [Time frame: Approximately 2 years]
• Phase 1b: Objective Response Rate (ORR) [Time frame: Approximately 2 years]

Secondary outcome measures (12)

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

Eligibility criteria

Inclusion criteria

• 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

Exclusion criteria

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

China · 47 centers

• The Second Hospital of Anhui Medical University — Hefei
• Cancer Hospital Chinese Academy of Medical Sciences — Beijing
• Beijing Cancer Hospital — Beijing
• Peking Union Medical College Hospital — Beijing
• Beijing Chest Hospital, Capital Medical University — Beijing
• Chongqing University Cancer Hospital — Chongqing
• Fujian Cancer Hospital — Fuzhou
• The First Affiliated Hospital of Xiamen University — Xiamen
• … and 39 more centers

United States · 11 centers

• 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
• … and 3 more centers

Brazil · 8 centers

• 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 centers

Center list to be confirmed — check the primary protocol.

Australia · 5 centers

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

France · 5 centers

• 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

Malaysia · 5 centers

• Hospital Pulau Pinang — George Town
• Hospital Raja Perempuan Zainab Ii — Johor Bahru
• Hospital Kuala Lumpur — Kuala Lumpur
• … and 2 more centers

Thailand · 5 centers

Center list to be confirmed — check the primary protocol.

Spain · 4 centers

Center list to be confirmed — check the primary protocol.

Denmark · 1 center

• Rigshospitalet — Copenhagen

Moldova · 1 center

Center list to be confirmed — check the primary protocol.

Identifiers

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

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)
• NMPA/CDE CTR20244451 (chinadrugtrials.org.cn platform)

View this study on ClinicalTrials.gov ↗