Clinical Trials /

Study of Safety, Pharmacokinetics, and Antitumor Activity of BGB-3245 in Participants With Advanced or Refractory Tumors

NCT04249843

Description:

The purpose of this study is to evaluate the safety, tolerability, and antitumor activity of BGB-3245 in participants with advanced or refractory tumors harboring specific v-RAF murine sarcoma viral oncogene homolog B (B-RAF) genetic mutations.

Related Conditions:
  • Malignant Solid Tumor
  • Melanoma
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of Safety, Pharmacokinetics, and Antitumor Activity of BGB-3245 in Participants With Advanced or Refractory Tumors
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: BGB-3245-AU-001
  • NCT ID: NCT04249843

Conditions

  • Solid Tumor
  • B-Raf Mutation-Related Tumors

Interventions

DrugSynonymsArms
BGB-3245Phase 1a: Dose Escalation

Purpose

The purpose of this study is to evaluate the safety, tolerability, and antitumor activity of BGB-3245 in participants with advanced or refractory tumors harboring specific v-RAF murine sarcoma viral oncogene homolog B (B-RAF) genetic mutations.

Detailed Description

      This is a first-in-human, Phase 1a/1b (dose escalation and expansion) study of BGB-3245 in
      participants with tumors harboring B-RAF mutations that are likely to respond to a RAF dimer
      inhibitor. BGB-3245 is a second-generation B-RAF inhibitor that has demonstrated potent
      inhibitory activity against the RAF family of serine/threonine kinases preclinically. In
      preclinical studies, BGB-3245 showed it inhibited tumor cell lines harboring non-V600 B-RAF
      mutations; it was also active towards B-RAF/MAP-ERK Kinase (MEK) inhibitor-resistant tumors.

      Phase 1a will consist of a dose-escalation and dose-finding component to establish the MTD
      and/or RP2D and to evaluate the pharmacokinetics of BGB-3245 3245 in participants with MAPK
      pathway aberrations. Phase 1b will consist of an expansion component to further evaluate the
      pharmacokinetics, safety, and tolerability of BGB-3245 at the RP2D and to assess the
      preliminary antitumor activity of the compound in participants with select tumor types and
      B-RAF mutational status.
    

Trial Arms

NameTypeDescriptionInterventions
Phase 1a: Dose EscalationExperimentalBGB-3245 administered orally (PO) as a continuous daily administration, in 28 day and 30 day cycles
  • BGB-3245
Phase 1b, Group 1: Dose Expansion, non-V600 B-RAF mutationsExperimentalBGB-3245 administered orally (PO) as a continuous daily administration, in 28 day and 30 day cycles in participants with non-V600 B-RAF mutations including RAF fusions
  • BGB-3245
hase 1b, Group 2: Dose Expansion, B-RAF V600 mutationsExperimentalBGB-3245 administered orally (PO) as a continuous daily administration, in 28 day and 30 day cycles in participants with B-RAF V600 mutated melanoma or NSCLC B-RAF and/or MEK inhibitor resistant tumors (i.e. have progressed on a B-RAF-inhibitor and/or MEK-inhibitor)
  • BGB-3245

Eligibility Criteria

        Key Inclusion Criteria:

        1. Participants with histologically or cytologically 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:

        a. Phase 1a: Participants with a known mutation status and tumor harboring an oncogenic
        B-RAF or K-RAS/N-RAS mutation, or any other MAPK pathway aberrations. In Phase 1a, the
        study recruitment will be limited to approximately one third (1/3) participants with
        K-RAS/N-RAS mutation, and among these participants the study recruitment will be limited to
        approximately one third (1/3) colorectal cancer (CRC) or pancreatic participants.

        a. Phase 1b: participants must have a known mutation status and meet one of the following
        criteria according to the group they are enrolled into:

          1. Group 1: participants with solid tumors with non-V600 B-RAF mutations including RAF
             fusions,; or

          2. Group 2: participants with B-RAF V600 mutated melanoma or non-small cell lung cancer
             (NSCLC), and have progressed on a B-RAF-inhibitor and/or MEK-inhibitor resistant
             tumors (i.e., mitogen-activated protein kinase/extracellular signal regulated kinase)
             inhibitor resistant tumors.

        2. Participants must provide tumor tissue sample (archival tumor tissue or agree to a fresh
        tumor biopsy) for mutation and biomarkers analysis 3. Participants must have measurable
        disease as defined per RECIST v1.1. 4. Eastern Cooperative Oncology Group performance
        status of ≤1 at Screening. 5. Adequate hematologic and organ function, as indicated by the
        following laboratory values, prior to Cycle 1 Day 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. Leptomeningeal disease or untreated/unstable brain metastasis except participants with
             previously treated brain metastasis who are radiologically stable (imaging evidence
             required), asymptomatic and have been off steroids and antiseizure medications for
             longer than 28 days prior to Cycle 1 Day 1 are permitted.

          5. Any unstable, preexisting major medical condition that in the opinion of the
             investigator contraindicates the use of an IMP, including known human immunodeficiency
             virus (HIV) or active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
             Participants who are hepatitis B surface antigen (HBsAg) positive or HCV antibody
             positive at Screening may be enrolled only if HBV DNA titers <500 IU/mL or negative
             HCV RNA polymerase chain reaction test, respectively.

        NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase 1a: Number of Participants and Severity Experiencing Adverse Events (AEs)
Time Frame:Up to 30 days after the last dose of study drug
Safety Issue:
Description:The MTD is defined as the highest dose evaluated for which the estimated toxicity rate is closest to the target toxicity rate of 33%.

Secondary Outcome Measures

Measure:Phase 1a: Overall Response Rate (ORR) as Assessed by the Investigator
Time Frame:Up to 24 months
Safety Issue:
Description:
Measure:Phase 1a: Duration of Response (DOR) as Assessed by the Investigator
Time Frame:Up to 24 months
Safety Issue:
Description:
Measure:Phase 1a: Clinical Benefit Rate (CBR) as Assessed by the Investigator
Time Frame:Up to 24 months
Safety Issue:
Description:
Measure:Phase 1a: Best Overall Response (BOR) as Assessed by the Investigator
Time Frame:Up to 24 months
Safety Issue:
Description:
Measure:Phase 1a: Duration of Stable Disease (DSD)
Time Frame:Up to 24 months
Safety Issue:
Description:
Measure:Phase 1a: Progression Free Survival (PFS)
Time Frame:Up to 24 months
Safety Issue:
Description:
Measure:Phase 1a: Plasma Concentration of BGB-3245
Time Frame:Within 60 minutes predose up to 72 hours postdose
Safety Issue:
Description:
Measure:Phase 1a: Maximum Observed Plasma Concentration (Cmax) of BGB-3245
Time Frame:Within 60 minutes predose up to 72 hours postdose
Safety Issue:
Description:
Measure:Phase 1a: Time to Maximum Plasma Concentration (Tmax) of BGB-3245
Time Frame:60 minutes predose up to 72 hours postdose
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure:Phase 1a: Drug Clearance (CL/F) of BGB-3245
Time Frame:60 minutes predose up to 72 hours postdose
Safety Issue:
Description:
Measure:Phase 1a: Apparent Volume of Distribution (Vz/F) of BGB-3245
Time Frame:60 minutes predose up to 72 hours postdose
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure:Phase 1a: Steady State Maximum Observed Plasma Concentration (Cmax, ss) of BGB-3245
Time Frame:60 minutes predose up to 72 hours postdose
Safety Issue:
Description:
Measure:Phase 1a: Steady State Time to Maximum Plasma Concentration (Tmax, ss) of BGB-3245
Time Frame:60 minutes predose up to 72 hours postdose
Safety Issue:
Description:
Measure:Phase 1b: Progression-free survival (PFS) as Assessed by the Investigator
Time Frame:Up to 36 months
Safety Issue:
Description:
Measure:Phase 1b: Duration of Response (DOR) as Assessed by the Investigator
Time Frame:Up to 24 months
Safety Issue:
Description:
Measure:Phase 1b: Disease-Control Rate (DCR) as Assessed by the Investigator
Time Frame:Up to 24 months
Safety Issue:
Description:
Measure:Phase 1b: Clinical Benefit Rate (CBR) as Assessed by the Investigator
Time Frame:Up to 24 months
Safety Issue:
Description:
Measure:Phase 1b: Overall Survival
Time Frame:Up to 36 months
Safety Issue:
Description:
Measure:Phase 1b: Number of Participants Experiencing Adverse Events (AEs)
Time Frame:Up to 30 days after the last dose of study drug
Safety Issue:
Description:
Measure:Phase 1b: Number of Participants Experiencing Serious Adverse Events (SAEs)
Time Frame:Up to 30 days after the last dose of study drug
Safety Issue:
Description:
Measure:Phase 1b: Plasma Concentration of BGB-3245
Time Frame:60 minutes predose up to 3 hours postdose
Safety Issue:
Description:
Measure:Phase 1b: Steady State Trough Observed Plasma Concentration (Ctrough, SS) of BGB-3245
Time Frame:60 minutes predose up to 72 hours postdose
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:MapKure, LLC

Trial Keywords

  • BGB3245
  • B-RAF inhibitor
  • B-RAF
  • K-RAS
  • N-RAS
  • Mitogen Activated Protein Kinase (MAPK) Pathway

Last Updated

August 6, 2020