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

NCT06589596
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Phase
Phase 1
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Recruitment status
Recruiting
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Participants
525
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Lead sponsor
BeOne Medicines
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Start date
2025-01-10
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Number of sites
98
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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 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.
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Short title
An Investigational Study of BGB-58067 As a Single Agent and in Combination With Anticancer Agents in Participants With Advanced Solid Tumors
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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
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Control arm
Open label
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Registry reports results
No
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Listing at source
Listed
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Recruitment status
Recruiting
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Phase
Phase 1
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Study type
Interventional
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Completion date
2027-09-30
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First posted
2024-09-19
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Registry last updated
2026-07-22
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Primary completion date
2027-09-30
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Start date
2025-01-10
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Participants
525
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Participant count basis
Estimated
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Planned participants
525
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Protocol amendments
4
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Number of sites
98
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Data monitoring committee
No
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Registry sponsor category
Industry
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Lead sponsor
BeOne Medicines
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Source registry
ClinicalTrials.gov
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Registry ID
NCT06589596
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ClinicalTrials.gov ID
NCT06589596
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Registry record
Open registry record
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Allocation
Not randomised
Model
Sequential
Purpose
Treatment
Masking
No masking
Sources for study design
clinicaltrials.gov

  1. 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 13 months)

    Number of participants with AEs and SAEs, including findings from physical examinations, electrocardiograms (ECGs), and laboratory assessments.

  2. Phase 1a: Number of Participants with Adverse Events that meet Dose-Limiting Toxicity (DLT) criteria

    Timeframe: Approximately 1 month

  3. 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

    Timeframe: Approximately 1 month

    MTD is defined as the highest dose evaluated for which estimated toxicity rate is the closest to the target toxicity rate. MAD is defined as the highest dose administered if MTD is not reached. Note: BGB-58067 + BG-89894 combination has been discontinued.

  4. 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

    Timeframe: Approximately 13 months

    RDFE of BGB-58067 alone, in combination with BG-89894, and in combination with standard of care therapy will be determined based upon the MTD or MAD. Note: BGB-58067 + BG-89894 combination has been discontinued.

  5. Phase 1b: Recommended Phase 2 Dose (RP2D) of BGB-58067 alone and in combination with standard of care therapy

    Timeframe: Approximately 2 years

    RP2D established from Phase 1a for BGB-58067 alone and in combination with standard of care therapy for administration in selected tumor types.

  6. Phase 1b: Objective Response Rate (ORR)

    Timeframe: Approximately 2 years

    ORR is defined as the percentage of participants with confirmed complete response (CR) or partial response (PR), as assessed by the investigator.

  1. Phase 1a: Objective Response Rate (ORR)

    Timeframe: Approximately 2 years

    ORR is defined as the percentage of participants with confirmed CR or PR, as assessed by the investigator.

  2. Phase 1a and 1b: Maximum observed plasma concentration (Cmax) of BGB-58067

    Timeframe: Approximately 2 months

  3. Phase 1a and 1b: Minimum observed plasma concentration (Cmin) of BGB-58067

    Timeframe: Approximately 9 months

  4. Phase 1a and 1b: Time to reach maximum observed plasma concentration (Tmax) of BGB-58067

    Timeframe: Approximately 2 months

  5. Phase 1a and 1b: Apparent oral clearance (CL/F) for BGB-58067

    Timeframe: Approximately 2 months

  6. Phase 1a and 1b: Half-life (t1/2) of BGB-58067

    Timeframe: Approximately 2 months

  7. Phase 1a and 1b: Area under the concentration-time curve (AUC) of BGB-58067

    Timeframe: Approximately 2 months

  8. Phase 1a and 1b: Apparent volume of distribution (Vz/F) for BGB-58067

    Timeframe: Approximately 2 months

  9. Phase 1a and 1b: Accumulation ratio (AR) for BGB-58067

    Timeframe: Approximately 2 months

  10. Phase 1a and 1b: Plasma concentrations of BGB-58067

    Timeframe: Approximately 9 months

  11. Phase 1a and 1b: Duration of Response (DOR)

    Timeframe: Approximately 2 years

    DOR is defined as the time from the first determination of an objective response until first documentation of progression or death, whichever occurs first, as assessed by the investigator.

  12. Phase 1a and 1b: Disease Control Rate (DCR)

    Timeframe: Approximately 2 years

    DCR is defined as the percentage of participants with best overall response of a CR, PR, and stable disease, as assessed by the investigator.

  13. 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 13 months)

    Number of participants with AEs and SAEs, including findings from physical examinations, electrocardiograms (ECGs), and laboratory assessments.

  14. Phase 1b: Progression-Free Survival (PFS)

    Timeframe: Approximately 2 years

    PFS is defined as the time from the date of the first dose of study drug to the date of first documentation of progressive disease assessed by investigator or death, whichever occurs first, as assessed by the investigator.

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Adults, Older adults
Minimum age
18 Years
Healthy volunteers
No

  • 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

  • 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.

Sources for eligibility
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  • Usc Norris Comprehensive Cancer Center (Nccc)Los Angeles, United StatesRecruiting
  • AdventhealthCelebration, United StatesRecruiting
  • Dana Farber Cancer InstituteBoston, United StatesRecruiting
  • Washington University School of MedicineSt Louis, United StatesRecruiting
  • Nyu Langone HealthNew York, United StatesRecruiting
  • Columbia University Medical CenterNew York, United StatesRecruiting
  • Sidney Kimmel Cancer CenterPhiladelphia, United StatesRecruiting
  • Tennessee Oncology, Pllc NashvilleNashville, United StatesRecruiting
  • The University of Texas Md Anderson Cancer CenterHouston, United StatesRecruiting
  • Next DallasIrving, United StatesRecruiting
  • Next VirginiaFairfax, United StatesRecruiting
  • Blacktown Cancer and Haematology CentreBlacktown, AustraliaRecruiting
  • Princess Alexandra HospitalWoolloongabba, AustraliaRecruiting
  • Monash HealthClayton, AustraliaRecruiting
  • Austin HealthHeidelberg, AustraliaRecruiting
  • Linear Clinical ResearchNedlands, AustraliaRecruiting
  • Fundacao Pio Xii Hospital de Amor de BarretosBarretos, BrazilRecruiting
  • Fundacao Universidade de Caxias Do SulCaxias do Sul, BrazilRecruiting
  • Centro Gaucho Integrado de Oncologia Hospital Mae de DeusPorto Alegre, BrazilRecruiting
  • Hospital Sao Lucas Da PucrsPorto Alegre, BrazilRecruiting
  • Ensino E Terapia de Inovacao Clinica Amo EticaSalvador, BrazilRecruiting
  • Icesp Instituto Do Cancer Do Estado de Sao Paulo Octavio Frias de OliveiraSão Paulo, BrazilRecruiting
  • Nucleo de Pesquisa E Ensino Da Rede Sao CamiloSão Paulo, BrazilRecruiting
  • Sociedade Beneficente Israelita Brasileira Hospital Albert EinsteinSão Paulo, BrazilRecruiting
  • The Second Hospital of Anhui Medical UniversityHefei, ChinaRecruiting

And 73 more, listed on the interactive page.

Sources for sites
clinicaltrials.gov

  • 2024-515307-19-00
  • CTR20244451
Sources for references
clinicaltrials.gov

Related records

Drugs (1)

Lead sponsors (1)