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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04249843




Registration number
NCT04249843
Ethics application status
Date submitted
21/01/2020
Date registered
31/01/2020

Titles & IDs
Public title
Study of Safety, Pharmacokinetics, and Antitumor Activity of BGB-3245 in Participants With Advanced or Refractory Tumors
Scientific 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
Secondary ID [1] 0 0
BGB-3245-AU-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Solid Tumor 0 0
B-Raf Mutation-Related Tumors 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - BGB-3245

Experimental: Phase 1a: Dose Escalation - BGB-3245 administered orally (PO)

Experimental: Phase 1b, Group 1: Dose Expansion - BGB-3245 administered orally (PO)


Treatment: Drugs: BGB-3245
administered orally (PO)
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Phase 1a: Number of Participants and Severity Experiencing Adverse Events (AEs)
Timepoint [1] 0 0
Up to 30 days after the last dose of study drug
Primary outcome [2] 0 0
Phase 1a: Number of Participants and Severity Experiencing Serious Adverse Events (SAEs)
Timepoint [2] 0 0
Up to 30 days after the last dose of study drug
Primary outcome [3] 0 0
Phase 1a: number of Participants Experiencing AEs meeting protocol defined Dose-Limiting Toxicity (DLT) criteria
Timepoint [3] 0 0
From Cycle 1 Day to the end of Cycle 1 (Cycle 1 is 30 days)
Primary outcome [4] 0 0
Phase 1a: Maximum Tolerated Dose (MTD) of BGB-3245, and the recommended Phase 2 Dose (RP2D) for BGB-3245
Timepoint [4] 0 0
From Cycle 1 Day to the end of Cycle 1 (Cycle 1 is 30 days)
Primary outcome [5] 0 0
Phase 1b: Recommended Phase 2 dose (RP2D) of BGB-3245
Timepoint [5] 0 0
From Cycle 1 Day to the end of Cycle 1 (Cycle 1 is 30 days)
Primary outcome [6] 0 0
Phase 1b: Objective Response Rate (ORR) as assessed by the investigator
Timepoint [6] 0 0
Up to 24 months
Secondary outcome [1] 0 0
Phase 1a: Overall Response Rate (ORR) as Assessed by the Investigator
Timepoint [1] 0 0
Up to 24 months
Secondary outcome [2] 0 0
Phase 1a: Duration of Response (DOR) as Assessed by the Investigator
Timepoint [2] 0 0
Up to 24 months
Secondary outcome [3] 0 0
Phase 1a: Clinical Benefit Rate (CBR) as Assessed by the Investigator
Timepoint [3] 0 0
Up to 24 months
Secondary outcome [4] 0 0
Phase 1a: Best Overall Response (BOR) as Assessed by the Investigator
Timepoint [4] 0 0
Up to 24 months
Secondary outcome [5] 0 0
Phase 1a: Duration of Stable Disease (DSD)
Timepoint [5] 0 0
Up to 24 months
Secondary outcome [6] 0 0
Phase 1a: Progression Free Survival (PFS)
Timepoint [6] 0 0
Up to 24 months
Secondary outcome [7] 0 0
Phase 1a: Plasma Concentration of BGB-3245
Timepoint [7] 0 0
Within 60 minutes predose up to 72 hours postdose
Secondary outcome [8] 0 0
Phase 1a: Maximum Observed Plasma Concentration (Cmax) of BGB-3245
Timepoint [8] 0 0
Within 60 minutes predose up to 72 hours postdose
Secondary outcome [9] 0 0
Phase 1a: Time to Maximum Plasma Concentration (Tmax) of BGB-3245
Timepoint [9] 0 0
60 minutes predose up to 72 hours postdose
Secondary outcome [10] 0 0
Phase 1a: Time Taken for Half the Initial Dose Administered To Be Eliminated From The Body (T1/2) of BGB-3245
Timepoint [10] 0 0
60 minutes predose up to 72 hours postdose
Secondary outcome [11] 0 0
Phase 1a: Area Under the Concentration-Time Curve of 0-infinity Days (AUC0-inf) of BGB-3245
Timepoint [11] 0 0
60 minutes predose up to 72 hours postdose
Secondary outcome [12] 0 0
Phase 1a:Area Under the Concentration-Time Curve of 0-Last hour (AUC0-last) of BGB-3245
Timepoint [12] 0 0
60 minutes predose up to 72 hours postdose
Secondary outcome [13] 0 0
Phase 1a: Drug Clearance (CL/F) of BGB-3245
Timepoint [13] 0 0
60 minutes predose up to 72 hours postdose
Secondary outcome [14] 0 0
Phase 1a: Apparent Volume of Distribution (Vz/F) of BGB-3245
Timepoint [14] 0 0
60 minutes predose up to 72 hours postdose
Secondary outcome [15] 0 0
Phase 1a: Steady State Area Under the Concentration-Time Curve of 0- Last hour (AUCLast, ss) of BGB-3245
Timepoint [15] 0 0
60 minutes predose up to 72 hours postdose
Secondary outcome [16] 0 0
Phase 1a: Steady State Maximum Observed Plasma Concentration (Cmax, ss) of BGB-3245
Timepoint [16] 0 0
60 minutes predose up to 72 hours postdose
Secondary outcome [17] 0 0
Phase 1a: Steady State Time to Maximum Plasma Concentration (Tmax, ss) of BGB-3245
Timepoint [17] 0 0
60 minutes predose up to 72 hours postdose
Secondary outcome [18] 0 0
Phase 1b: Progression-free survival (PFS) as Assessed by the Investigator
Timepoint [18] 0 0
Up to 36 months
Secondary outcome [19] 0 0
Phase 1b: Duration of Response (DOR) as Assessed by the Investigator
Timepoint [19] 0 0
Up to 24 months
Secondary outcome [20] 0 0
Phase 1b: Disease-Control Rate (DCR) as Assessed by the Investigator
Timepoint [20] 0 0
Up to 24 months
Secondary outcome [21] 0 0
Phase 1b: Duration of Stable Disease (DSD) as Assessed by the Investigator
Timepoint [21] 0 0
Up to 24 months
Secondary outcome [22] 0 0
Phase 1b: Clinical Benefit Rate (CBR) as Assessed by the Investigator
Timepoint [22] 0 0
Up to 24 months
Secondary outcome [23] 0 0
Phase 1b: Overall Survival
Timepoint [23] 0 0
Up to 36 months
Secondary outcome [24] 0 0
Phase 1b: Number of Participants Experiencing Adverse Events (AEs)
Timepoint [24] 0 0
Up to 30 days after the last dose of study drug
Secondary outcome [25] 0 0
Phase 1b: Number of Participants Experiencing Serious Adverse Events (SAEs)
Timepoint [25] 0 0
Up to 30 days after the last dose of study drug
Secondary outcome [26] 0 0
Phase 1b: Plasma Concentration of BGB-3245
Timepoint [26] 0 0
60 minutes predose up to 3 hours postdose
Secondary outcome [27] 0 0
Phase 1b: Steady State Trough Observed Plasma Concentration (Ctrough, SS) of BGB-3245
Timepoint [27] 0 0
60 minutes predose up to 72 hours postdose

Eligibility
Key inclusion criteria
Key

1. Participants with histologically confirmed advanced or metastatic solid tumor who had disease progression during or after systemic anticancer therapies that previously demonstrated clinical benefit (eg, improved survival) in a representative population, or are unable to receive standard therapy(ies). 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 tumors harboring the mutation of the neuroblastoma RAS viral oncogene homolog (NRAS) gene or the Kirsten rat sarcoma virus oncogene homolog (KRAS) are eligible for Part 1a. For participants with KRAS mutations, tumor types of colorectal cancer (CRC) and pancreatic cancer are excluded.
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 tumor types other than CRC that harbor BRAF V600 mutations who have been treated and progressed on prior BRAF and/or mitogen activated protein kinase (MEK) inhibition.

a. Participants must have received the last dose of prior BRAF and/or MEK inhibitor therapy within 90 days of initiation of BGB-3245 study treatment (Cycle 1 Day 1)

II. Group 2: participants with advanced solid tumors harboring a BRAF Class II mutation or a BRAF fusion mutation.
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)
3. Participants must have radiologically measurable disease as defined by RECIST v1.1
4. Eastern Cooperative Oncology Group (ECOG) performance status of =1
5. Adequate organ function and no transfusions within 14 days of first dose

Key
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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. Systemic chemotherapy within 4 weeks or 6 weeks for nitrosourea, mitomycin 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. Severe or uncontrolled systemic disease.
4. Clinically significant cardiac disease within 6 months of signing the ICF
5. CNS metastases, leptomeningeal carcinomatosis or untreated spinal cord compression.
6. Inability to swallow oral medicines.
7. Any unstable, preexisting major medical condition, including known human immunodeficiency virus (HIV) or active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
8. Systemic anti-cancer therapy within 2 weeks or 5 half-lives before first dose.
9. Major surgical procedure or significant traumatic injury within 4 weeks prior to the first dose or anticipates need for major surgery while on study.

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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
17/02/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/06/2025
Actual
Sample size
Target
114
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,PerthVIC
Recruitment hospital [1] 0 0
Blacktown Hospital - Blacktown
Recruitment hospital [2] 0 0
The Kinghorn Cancer Centre, St Vincent Hospital Sydney - Sydney
Recruitment hospital [3] 0 0
One Clinical Research - Nedlands
Recruitment hospital [4] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 0 0
2148 - Blacktown
Recruitment postcode(s) [2] 0 0
2010 - Sydney
Recruitment postcode(s) [3] 0 0
6009 - Nedlands
Recruitment postcode(s) [4] 0 0
2010 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Louisiana
Country [3] 0 0
United States of America
State/province [3] 0 0
Massachusetts
Country [4] 0 0
United States of America
State/province [4] 0 0
New York
Country [5] 0 0
United States of America
State/province [5] 0 0
Texas
Country [6] 0 0
United States of America
State/province [6] 0 0
Virginia

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
MapKure, LLC
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
MapKure
Address 0 0
Country 0 0
Phone 0 0
1-877-828-5568
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04249843