Clinical trial NCT06589596: An Investigational Study of BGB-58067 in Participants With Advanced Solid Tumors
Official title: A Phase 1a/b Study Investigating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Antitumor Activity of BGB-58067, an MTA-Cooperative PRMT5 Inhibitor in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumor
Keywords: advanced solid tumor
BGB-58067
MTAP deficiency
Lead sponsor: BeiGene
Sponsor class: INDUSTRY
First posted: 2024-09-19
Enrollment: 92
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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 as monotherapy 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 as monotherapy in participants with advanced solid tumors and with MTAP deficiency.

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 advanced, metastatic, or unresectable solid tumors, who have previously received standard systemic therapy or for whom treatment is not available or not tolerated
* Adequate organ function

Exclusion Criteria:

* Prior treatment with any 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
* High cardiovascular risk factors
* QTcF \> 470 ms based on the screening triplicate 12-lead ECG records
* 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.

Primary outcomes:
measure: Phase 1a: Number of Participants with Adverse Events and Serious Adverse Events
timeFrame: 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 2 years)
measure: Phase 1a: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD)
timeFrame: Approximately 1.5 years
measure: Phase 1a: Recommended Dose(s) for Expansion (RDFE[s]) of BGB-58067
timeFrame: Approximately 2 years
measure: Phase 1b: Recommended Phase 2 Dose (RP2D) of BGB-58067
timeFrame: Approximately 2 years
measure: Phase 1b: Objective Response Rate (ORR)
timeFrame: Approximately 2 years
Secondary outcomes:
measure: Phase 1a: Objective Response Rate (ORR)
timeFrame: Approximately 2 years
measure: Phase 1a: Maximum observed plasma concentration (Cmax) of BGB-58067
timeFrame: Approximately 2 years
measure: Phase 1a: Minimum observed plasma concentration (Cmin) of BGB-58067
timeFrame: Approximately 2 years
measure: Phase 1a: Time to reach maximum observed plasma concentration (Tmax) of BGB-58067
timeFrame: Approximately 2 years
measure: Phase 1a: Apparent oral clearance (CL/F) for BGB-58067
timeFrame: Approximately 2 years
measure: Phase 1a: Half life (t1/2) of BGB-58067
timeFrame: Approximately 2 years
measure: Phase 1a: Area under the concentration-time curve (AUC) of BGB-58067
timeFrame: Approximately 2 years
measure: Phase 1a: Apparent volume of distribution (Vz/F) for BGB-58067
timeFrame: Approximately 2 years
measure: Phase 1a: Accumulation ratio (AR) for BGB-58067
timeFrame: Approximately 2 years
measure: Phase 1a and 1b: plasma concentrations of BGB-58067
timeFrame: Approximately 2 years
measure: Phase 1a and 1b: Duration of Response (DOR)
timeFrame: Approximately 2 years
measure: Phase 1a and 1b: Disease Control Rate (DCR)
timeFrame: Approximately 2 years
measure: Phase 1b: Number of Participants with AEs and SAEs
timeFrame: 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 2 years)
measure: Phase 1b: Progression-Free Survival (PFS)
timeFrame: Approximately 2 years
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Usc Norris Comprehensive Cancer Center (Nccc)
state: California
city: Celebration
country: United States
facility: Adventhealth
state: Florida
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: New York
country: United States
facility: Laura and Isaac Perlmutter Cancer Center At Nyu Langone Health
state: New York
city: Philadelphia
country: United States
facility: Sidney Kimmel Cancer Center
state: Pennsylvania
city: Houston
country: United States
facility: The University of Texas Md Anderson Cancer Center
state: Texas
city: Irving
country: United States
facility: Next Dallas
state: Texas
city: Fairfax
country: United States
facility: Next Virginia
state: Virginia
city: Blacktown
country: Australia
facility: Blacktown Cancer and Haematology Centre
state: New South Wales
city: Clayton
country: Australia
facility: Monash Health
state: Victoria
city: Heidelberg
country: Australia
facility: Austin Health
state: Victoria
city: Nedlands
country: Australia
facility: Linear Clinical Research
state: Western Australia
city: Hefei
country: China
facility: The Second Hospital of Anhui Medical University
state: Anhui
city: Beijing
country: China
facility: Cancer Hospital Chinese Academy of Medical Sciences
state: Beijing
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Fuzhou
country: China
facility: Fujian Cancer Hospital
state: Fujian
city: Guangzhou
country: China
facility: Sun Yat Sen University Cancer Center
state: Guangdong
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
state: Heilongjiang
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Henan
city: Wuhan
country: China
facility: Union Hospital of Tongji Medical College, Huazhong University of Science and Technology
state: Hubei
city: Nanjing
country: China
facility: Jiangsu Province Hospital
state: Jiangsu
city: Nanchang
country: China
facility: Jiangxi Cancer Hospital
state: Jiangxi
city: Shenyang
country: China
facility: The First Hospital of China Medical University
state: Liaoning
city: Shanghai
country: China
facility: Shanghai East Hospital Branch Hospital
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Pulmonary Hospital
state: Shanghai
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Centerpudong
state: Shanghai
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
state: Sichuan
city: Hangzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University School of Medicine
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Bordeaux
country: France
facility: Centre de Lutte Contre Le Cancer Institut Bergonie
city: Marseille
country: France
facility: Institut Paoli Calmettes
city: Paris
country: France
facility: Institut Curie Paris
city: St Herblain
country: France
facility: Institut de Cancerologie de Louest
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: GangnamGu
country: Korea, Republic of
facility: Samsung Medical Center
state: Seoul Teugbyeolsi
city: SeodaemunGu
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
state: Seoul Teugbyeolsi
city: SongpaGu
country: Korea, Republic of
facility: Asan Medical Center
state: Seoul Teugbyeolsi
city: Barcelona
country: Spain
facility: Hospital Universitario Vall Dhebron
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Madrid
country: Spain
facility: Start Madrid Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: Hospital Universitario Hm Madrid Sanchinarro
Study officials:
affiliation: BeiGene
name: Study Director
role: STUDY_DIRECTOR
References: