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Purpose

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.

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

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.

Study Design

Phase
Phase 1
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Sequential Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Phase 1a: BGB-58067 Monotherapy Dose Escalation and Safety Expansion 		Sequential cohorts of increasing dose levels of BGB-58067 as monotherapy will be evaluated.
  • Drug: BGB-58067
    Planned doses administered on specified days per protocol.
Experimental
Phase 1a: BGB-58067 + BG-89894 Combination Therapy Dose Escalation 		Sequential cohorts of increasing dose levels of BGB-58067 in combination with BG-89894 will be evaluated. Enrollment in this combination has been discontinued.
  • Drug: BGB-58067
    Planned doses administered on specified days per protocol.
  • Drug: BG-89894
    Planned doses administered on specified days per protocol.
Experimental
Phase 1a: BGB-58067 + Standard of Care Combination Therapy Dose Escalation 		Sequential cohorts of increasing dose levels of BGB-58067 in combination with standard of care therapy will be evaluated.
  • Drug: BGB-58067
    Planned doses administered on specified days per protocol.
  • Drug: Standard of Care Therapy
    Administered in accordance with relevant local guidelines and/or prescribing information.
Experimental
Phase 1b: Dose Expansion and Optimization 		Recommended Dose(s) for Expansion (RDFE[s]) of BGB-58067 alone and in combination with standard of care therapy will be evaluated for selected indications and regimen(s) based on emerging data.
  • Drug: BGB-58067
    Planned doses administered on specified days per protocol.
  • Drug: Standard of Care Therapy
    Administered in accordance with relevant local guidelines and/or prescribing information.

Recruiting Locations

Usc Norris Comprehensive Cancer Center (Nccc)
Los Angeles, California 90089-1019

Adventhealth
Celebration, Florida 34747-4606

Dana Farber Cancer Institute
Boston, Massachusetts 02215-5418

Washington University School of Medicine
St Louis, Missouri 63110-1010

Nyu Langone Health
New York, New York 10016-2708

Columbia University Medical Center
New York, New York 10032

Sidney Kimmel Cancer Center
Philadelphia, Pennsylvania 19107-4307

Tennessee Oncology, Pllc Nashville
Nashville, Tennessee 37203

The University of Texas Md Anderson Cancer Center
Houston, Texas 77030-4009

Next Dallas
Irving, Texas 75039-2743

Next Virginia
Fairfax, Virginia 22031

More Details

Status
Recruiting
Sponsor
BeOne Medicines

Study Contact

Study Director
1.877.828.5568
clinicaltrials@beonemed.com

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.