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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT04249843
Ethics application status
Date submitted
21/01/2020
Date registered
31/01/2020
Date last updated
29/09/2020

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) as a continuous daily administration, in 28 day and 30 day cycles

Experimental: Phase 1b, Group 1: Dose Expansion, non-V600 B-RAF mutations - BGB-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

Experimental: hase 1b, Group 2: Dose Expansion, B-RAF V600 mutations - BGB-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)


Treatment: Drugs: BGB-3245
Administered as specified in the treatment arm

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 - The MTD is defined as the highest dose evaluated for which the estimated toxicity rate is closest to the target toxicity rate of 33%.
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: Objective Response Rate (ORR) confirmed Complete Response and Partial Response
Timepoint [5] 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: Clinical Benefit Rate (CBR) as Assessed by the Investigator
Timepoint [21] 0 0
Up to 24 months
Secondary outcome [22] 0 0
Phase 1b: Overall Survival
Timepoint [22] 0 0
Up to 36 months
Secondary outcome [23] 0 0
Phase 1b: Number of Participants Experiencing Adverse Events (AEs)
Timepoint [23] 0 0
Up to 30 days after the last dose of study drug
Secondary outcome [24] 0 0
Phase 1b: Number of Participants Experiencing Serious Adverse Events (SAEs)
Timepoint [24] 0 0
Up to 30 days after the last dose of study drug
Secondary outcome [25] 0 0
Phase 1b: Plasma Concentration of BGB-3245
Timepoint [25] 0 0
60 minutes predose up to 3 hours postdose
Secondary outcome [26] 0 0
Phase 1b: Steady State Trough Observed Plasma Concentration (Ctrough, SS) of BGB-3245
Timepoint [26] 0 0
60 minutes predose up to 72 hours postdose

Eligibility
Key inclusion criteria
Key

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
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
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.

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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [2] 0 0
The Kinghorn Cancer Centre, St Vincent Hospital Sydney - Sydney
Recruitment postcode(s) [1] 0 0
2010 - Melbourne
Recruitment postcode(s) [2] 0 0
2010 - Sydney
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
New York
Country [2] 0 0
United States of America
State/province [2] 0 0
Texas

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

Ethics approval
Ethics application status

Summary
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 tumors harboring specific v-RAF murine
sarcoma viral oncogene homolog B (B-RAF) genetic mutations.
Trial website
https://clinicaltrials.gov/show/NCT04249843
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Brandon Beagle, MD
Address 0 0
BeiGene
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
clinicaltrials@mapkure.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04249843