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Trial record 1 of 1 for:    BGB-3245
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Study of Safety, Pharmacokinetics, and Antitumor Activity of BGB-3245 in Participants With Advanced or Refractory Tumors

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ClinicalTrials.gov Identifier: NCT04249843
Recruitment Status : Recruiting
First Posted : January 31, 2020
Last Update Posted : January 3, 2022
Sponsor:
Information provided by (Responsible Party):
MapKure, LLC

Tracking Information
First Submitted Date  ICMJE January 21, 2020
First Posted Date  ICMJE January 31, 2020
Last Update Posted Date January 3, 2022
Actual Study Start Date  ICMJE February 17, 2020
Estimated Primary Completion Date May 1, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 29, 2020)
  • Phase 1a: Number of Participants and Severity Experiencing Adverse Events (AEs) [ Time Frame: Up to 30 days after the last dose of study drug ]
  • Phase 1a: Number of Participants and Severity Experiencing Serious Adverse Events (SAEs) [ Time Frame: Up to 30 days after the last dose of study drug ]
  • Phase 1a: number of Participants Experiencing AEs meeting protocol defined Dose-Limiting Toxicity (DLT) criteria [ Time Frame: From Cycle 1 Day to the end of Cycle 1 (Cycle 1 is 30 days) ]
  • Phase 1a: Maximum Tolerated Dose (MTD) of BGB-3245, and the recommended Phase 2 Dose (RP2D) for BGB-3245 [ Time Frame: From Cycle 1 Day to the end of Cycle 1 (Cycle 1 is 30 days) ]
    The MTD is defined as the highest dose evaluated for which the estimated toxicity rate is closest to the target toxicity rate of 33%.
  • Phase 1b: Objective Response Rate (ORR) confirmed Complete Response and Partial Response [ Time Frame: Up to 24 months ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 13, 2021)
  • Phase 1a: Overall Response Rate (ORR) as Assessed by the Investigator [ Time Frame: Up to 24 months ]
  • Phase 1a: Duration of Response (DOR) as Assessed by the Investigator [ Time Frame: Up to 24 months ]
  • Phase 1a: Clinical Benefit Rate (CBR) as Assessed by the Investigator [ Time Frame: Up to 24 months ]
  • Phase 1a: Best Overall Response (BOR) as Assessed by the Investigator [ Time Frame: Up to 24 months ]
  • Phase 1a: Duration of Stable Disease (DSD) [ Time Frame: Up to 24 months ]
  • Phase 1a: Progression Free Survival (PFS) [ Time Frame: Up to 24 months ]
  • Phase 1a: Plasma Concentration of BGB-3245 [ Time Frame: Within 60 minutes predose up to 72 hours postdose ]
  • Phase 1a: Maximum Observed Plasma Concentration (Cmax) of BGB-3245 [ Time Frame: Within 60 minutes predose up to 72 hours postdose ]
  • Phase 1a: Time to Maximum Plasma Concentration (Tmax) of BGB-3245 [ Time Frame: 60 minutes predose up to 72 hours postdose ]
  • Phase 1a: Time Taken for Half the Initial Dose Administered To Be Eliminated From The Body (T1/2) of BGB-3245 [ Time Frame: 60 minutes predose up to 72 hours postdose ]
  • Phase 1a: Area Under the Concentration-Time Curve of 0-infinity Days (AUC0-inf) of BGB-3245 [ Time Frame: 60 minutes predose up to 72 hours postdose ]
  • Phase 1a:Area Under the Concentration-Time Curve of 0-Last hour (AUC0-last) of BGB-3245 [ Time Frame: 60 minutes predose up to 72 hours postdose ]
  • Phase 1a: Drug Clearance (CL/F) of BGB-3245 [ Time Frame: 60 minutes predose up to 72 hours postdose ]
  • Phase 1a: Apparent Volume of Distribution (Vz/F) of BGB-3245 [ Time Frame: 60 minutes predose up to 72 hours postdose ]
  • Phase 1a: Steady State Area Under the Concentration-Time Curve of 0- Last hour (AUCLast, ss) of BGB-3245 [ Time Frame: 60 minutes predose up to 72 hours postdose ]
  • Phase 1a: Steady State Maximum Observed Plasma Concentration (Cmax, ss) of BGB-3245 [ Time Frame: 60 minutes predose up to 72 hours postdose ]
  • Phase 1a: Steady State Time to Maximum Plasma Concentration (Tmax, ss) of BGB-3245 [ Time Frame: 60 minutes predose up to 72 hours postdose ]
  • Phase 1b: Progression-free survival (PFS) as Assessed by the Investigator [ Time Frame: Up to 36 months ]
  • Phase 1b: Duration of Response (DOR) as Assessed by the Investigator [ Time Frame: Up to 24 months ]
  • Phase 1b: Disease-Control Rate (DCR) as Assessed by the Investigator [ Time Frame: Up to 24 months ]
  • Phase 1b: Duration of Stable Disease (DSD) as Assessed by the Investigator [ Time Frame: Up to 24 months ]
  • Phase 1b: Clinical Benefit Rate (CBR) as Assessed by the Investigator [ Time Frame: Up to 24 months ]
  • Phase 1b: Overall Survival [ Time Frame: Up to 36 months ]
  • Phase 1b: Number of Participants Experiencing Adverse Events (AEs) [ Time Frame: Up to 30 days after the last dose of study drug ]
  • Phase 1b: Number of Participants Experiencing Serious Adverse Events (SAEs) [ Time Frame: Up to 30 days after the last dose of study drug ]
  • Phase 1b: Plasma Concentration of BGB-3245 [ Time Frame: 60 minutes predose up to 3 hours postdose ]
  • Phase 1b: Steady State Trough Observed Plasma Concentration (Ctrough, SS) of BGB-3245 [ Time Frame: 60 minutes predose up to 72 hours postdose ]
Original Secondary Outcome Measures  ICMJE
 (submitted: January 29, 2020)
  • Phase 1a: Overall Response Rate (ORR) as Assessed by the Investigator [ Time Frame: Up to 24 months ]
  • Phase 1a: Duration of Response (DOR) as Assessed by the Investigator [ Time Frame: Up to 24 months ]
  • Phase 1a: Clinical Benefit Rate (CBR) as Assessed by the Investigator [ Time Frame: Up to 24 months ]
  • Phase 1a: Best Overall Response (BOR) as Assessed by the Investigator [ Time Frame: Up to 24 months ]
  • Phase 1a: Duration of Stable Disease (DSD) [ Time Frame: Up to 24 months ]
  • Phase 1a: Progression Free Survival (PFS) [ Time Frame: Up to 24 months ]
  • Phase 1a: Plasma Concentration of BGB-3245 [ Time Frame: Within 60 minutes predose up to 72 hours postdose ]
  • Phase 1a: Maximum Observed Plasma Concentration (Cmax) of BGB-3245 [ Time Frame: Within 60 minutes predose up to 72 hours postdose ]
  • Phase 1a: Time to Maximum Plasma Concentration (Tmax) of BGB-3245 [ Time Frame: 60 minutes predose up to 72 hours postdose ]
  • Phase 1a: Time Taken for Half the Initial Dose Administered To Be Eliminated From The Body (T1/2) of BGB-3245 [ Time Frame: 60 minutes predose up to 72 hours postdose ]
  • Phase 1a: Area Under the Concentration-Time Curve of 0-infinity Days (AUC0-inf) of BGB-3245 [ Time Frame: 60 minutes predose up to 72 hours postdose ]
  • Phase 1a:Area Under the Concentration-Time Curve of 0-Last hour (AUC0-last) of BGB-3245 [ Time Frame: 60 minutes predose up to 72 hours postdose ]
  • Phase 1a: Drug Clearance (CL/F) of BGB-3245 [ Time Frame: 60 minutes predose up to 72 hours postdose ]
  • Phase 1a: Apparent Volume of Distribution (Vz/F) of BGB-3245 [ Time Frame: 60 minutes predose up to 72 hours postdose ]
  • Phase 1a: Steady State Area Under the Concentration-Time Curve of 0- Last hour (AUCLast, ss) of BGB-3245 [ Time Frame: 60 minutes predose up to 72 hours postdose ]
  • Phase 1a: Steady State Maximum Observed Plasma Concentration (Cmax, ss) of BGB-3245 [ Time Frame: 60 minutes predose up to 72 hours postdose ]
  • Phase 1a: Steady State Time to Maximum Plasma Concentration (Tmax, ss) of BGB-3245 [ Time Frame: 60 minutes predose up to 72 hours postdose ]
  • Phase 1b: Progression-free survival (PFS) as Assessed by the Investigator [ Time Frame: Up to 36 months ]
  • Phase 1b: Duration of Response (DOR) as Assessed by the Investigator [ Time Frame: Up to 24 months ]
  • Phase 1b: Disease-Control Rate (DCR) as Assessed by the Investigator [ Time Frame: Up to 24 months ]
  • Phase 1b: Clinical Benefit Rate (CBR) as Assessed by the Investigator [ Time Frame: Up to 24 months ]
  • Phase 1b: Overall Survival [ Time Frame: Up to 36 months ]
  • Phase 1b: Number of Participants Experiencing Adverse Events (AEs) [ Time Frame: Up to 30 days after the last dose of study drug ]
  • Phase 1b: Number of Participants Experiencing Serious Adverse Events (SAEs) [ Time Frame: Up to 30 days after the last dose of study drug ]
  • Phase 1b: Plasma Concentration of BGB-3245 [ Time Frame: 60 minutes predose up to 3 hours postdose ]
  • Phase 1b: Steady State Trough Observed Plasma Concentration (Ctrough, SS) of BGB-3245 [ Time Frame: 60 minutes predose up to 72 hours postdose ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Safety, Pharmacokinetics, and Antitumor Activity of BGB-3245 in Participants With Advanced or Refractory Tumors
Official Title  ICMJE A First-in-Human, Phase 1a/1b, Open Label, Dose-Escalation and Expansion Study to Investigate the Safety, Pharmacokinetics, and Antitumor Activity of the RAF Dimer Inhibitor BGB-3245 in Patients With Advanced or Refractory Tumors
Brief Summary The purpose of this study is to evaluate the safety, tolerability, and antitumor activity of BGB-3245 in participants with advanced or refractory solid tumors
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Solid Tumor
  • B-Raf Mutation-Related Tumors
Intervention  ICMJE Drug: BGB-3245
administered orally (PO)
Study Arms  ICMJE
  • Experimental: Phase 1a: Dose Escalation
    BGB-3245 administered orally (PO)
    Intervention: Drug: BGB-3245
  • Experimental: Phase 1b, Group 1: Dose Expansion
    BGB-3245 administered orally (PO)
    Intervention: Drug: BGB-3245
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 13, 2021)
168
Original Estimated Enrollment  ICMJE
 (submitted: January 29, 2020)
69
Estimated Study Completion Date  ICMJE June 1, 2023
Estimated Primary Completion Date May 1, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria:

  1. Participants with histologically confirmed advanced or metastatic solid tumor who have experienced disease progression during or after at least 1 line of prior systemic anticancer therapy, or for whom treatment is not available or not tolerated/acceptable to the participants. In addition, participants must meet the following eligibility criteria for the corresponding phase of the study:

    1. Phase 1a: participants with a known mutation status and tumor harboring an oncogenic mutation of the v-RAF murine sarcoma viral oncogene homolog B (BRAF) gene (the mutations of primary interest are the BRAF Class II mutation, Class III mutation or BRAF fusion). In addition, participants with melanoma harboring the mutation of the neuroblastoma RAS viral oncogene homolog (NRAS) gene are eligible for Part 1a.
    2. Phase 1b: participants must have a known mutation status and meet one of the following criteria according to the group they are enrolled into:

    i. Group 1: participants with solid tumors harboring a BRAF Class II mutation

    ii. Group 2: participants with solid tumors harboring a BRAF Class III mutation

    iii. Group 3: participants with solid tumors harboring a BRAF fusion mutation

    iv. Group 4: participants with cutaneous melanoma harboring a NRAS mutation

    v. Group 5: participants with cutaneous melanoma harboring a NRAS mutation that consent to paired fresh biopsies inhibitor resistant tumors.

  2. Participants must provide archival tumor tissue or agree to a fresh tumor biopsy for mutation and biomarkers analysis (fresh tumor biopsies are strongly recommended at Screening in participants with readily accessible tumor lesions who are not receiving anticoagulants).3. Patients must have radiologically measurable disease as defined per RECIST v1.1.

Key Exclusion Criteria:

  1. Participants receiving cancer therapy (chemotherapy or other systemic anticancer therapies, immunotherapy, radiation therapy, or surgery) at the time of Cycle 1 Day 1.
  2. All participants who have received prior systemic anticancer treatment within the following time frames will be excluded:

    1. Cyclical chemotherapy within a period of time that is shorter than the cycle length used for that treatment (i.e., 6 weeks for nitrosourea, mitomycin C) prior to Cycle 1 Day 1; and
    2. Biologic therapy (i.e., antibodies), continuous or intermittent small-molecule therapies, or any other investigational agents within a period of 5 times the half-life of the agent or ≤4 weeks (whichever is shorter) prior to Cycle 1 Day 1.
  3. History or presence of gastrointestinal disease or other condition known to interfere with the absorption, distribution, metabolism, or excretion of drugs.
  4. Current evidence of symptomatic CNS metastases, leptomeningeal carcinomatosis or untreated spinal cord compression. Asymptomatic treated or asymptomatic untreated brain metastases are allowed as long as patients are clinically stable.
  5. Any unstable, preexisting major medical condition that in the opinion of the investigator contraindicates the use of a study drug, including known human immunodeficiency virus (HIV) or active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: MapKure 1-877-828-5568 clinicaltrials@mapkure.com
Listed Location Countries  ICMJE Australia,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04249843
Other Study ID Numbers  ICMJE BGB-3245-AU-001
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Current Responsible Party MapKure, LLC
Original Responsible Party Same as current
Current Study Sponsor  ICMJE MapKure, LLC
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account MapKure, LLC
Verification Date December 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP