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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03905148




Registration number
NCT03905148
Ethics application status
Date submitted
3/04/2019
Date registered
5/04/2019
Date last updated
11/07/2019

Titles & IDs
Public title
Study of the Safety and Pharmacokinetics of BGB-283 and PD-0325901 in Patients With Advanced or Refractory Solid Tumors
Scientific title
A Phase 1b, Open-Label, Dose-escalation and Expansion Study to Investigate the Safety, Pharmacokinetics and Antitumor Activities of a RAF Dimer Inhibitor BGB-283 in Combination With MEK Inhibitor PD-0325901 in Patients With Advanced or Refractory Solid Tumors
Secondary ID [1] 0 0
BGB-283/PD-0325901-AU-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Solid Tumor, Adult 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - BGB-283 (lifirafenib)
Treatment: Drugs - PD-0325901

Experimental: Part A: Dose Level 1 - PD-0325901 at 2 mg once a day and BGB-283 (lifirafenib) at 15 mg once a day

Experimental: Part A: Dose Level 2 - PD-0325901 at 2 mg once a day and BGB-283 (lifirafenib) at 20 mg once a day

Experimental: Part A: Dose Level 3 - PD-0325901 at 4 mg once a day and BGB-283 (lifirafenib) at 20 mg once a day

Experimental: Part A: Dose Level 4 - PD-0325901 at 6 or 8 mg once a day and BGB-283 (lifirafenib) at 20 or 25 mg once a day depending on the safety and tolerability observed at Levels 1, 2, and 3

Experimental: Part B: Group 1 - Non-small cell lung cancer with confirmed K-RAS mutations, approximately 15 patients

Experimental: Part B: Group 2 - Endometrial cancer with confirmed K-RAS mutations, approximately 15 patients

Experimental: Part B: Group 3 - Tumor type of interest based on preliminary anti-tumor clinical activities observed in Part A, approximately 15 patients


Treatment: Drugs: BGB-283 (lifirafenib)
RAF Dimer Inhibitor

Treatment: Drugs: PD-0325901
MEK Inhibitor

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Adverse Events and Serious Adverse Events - Incidence and severity of AEs and SAEs and graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03
Timepoint [1] 0 0
Approximately 2 years from date of the patient enrollment
Primary outcome [2] 0 0
The incidence of DLT events and treatment-emergent AEs (TEAEs)
Timepoint [2] 0 0
Approximately 2 years from date of the patient enrollment
Primary outcome [3] 0 0
Objective response rate based on Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 in subjects with selected tumor types
Timepoint [3] 0 0
Approximately 2 years from date of the patient enrollment

Eligibility
Key inclusion criteria
1. Able to provide informed consent

2. Age 18 on day of signing informed consent form (ICF) or of the legal age of consent in
the jurisdiction in which the study is taking place

3. Advanced or metastatic, unresectable tumors who have experienced disease progression

- Part A: NSCLC, CRC, ovarian cancer, endometrial cancer, thyroid cancer, melanoma,
pancreatic cancer, and other)

- Part B: Group 1: NSCLC, Group 2: endometrial cancer, Group 3: Tumor types of
interest based on preliminary anti-tumor activities observed in Part A

4. Must have archival tumor tissue or agree to tumor biopsy

5. Measureable disease per RECIST 1.1

6. Eastern Cooperative Oncology Group performance status of greater than 1

7. Life expectancy is greater than 12 weeks at the of signing ICF.

8. Adequate organ function and no transfusion within 14 days of first dose.

9. Females are of non-child bearing potential or willing to use contraception.

10. Males vasectomized or agree to use contraception.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Central Nervous System metastasis

2. Any retinal pathology considered to be a risk factor for central serous retinopathy

3. History of glaucoma

4. Active parathyroid disorder or history of malignancy associated hypercalcemia

5. Clinically significant cardiac disease within the past 6 months of signing ICF.

6. LVEF less than 50%

7. Abnormal QT interval at Screening

8. Severe uncontrolled systemic disease

9. HIV

10. Clinically significant active or known history of liver disease. (Hepatitis B and
Hepatitis C)

11. Hemorrhage or bleeding event at NCI-CTCAE v4.03 Grade 3 or higher within 28 days of
first dose.

12. Increased serum calcium

13. Inability to swallow oral medications

14. Ongoing radiation therapy or radio-cytotoxic therapy within prior 4 weeks. No
immunotherapy,biologic therapy, hormonal, or molecular targeted therapy within prior 2
weeks

15. Concomitant systemic or glucocorticoid therapy

16. Concomitant vitamin D

17. Major surgical procedure or significant traumatic injury within 4 weeks prior to first
dose or anticipates need for major surgery while on study

18. Concomitant medicines that are strong CYP3A inhibitors

19. History of significant toxicity from another RAF, MEK, ERK inhibitor requiring
discontinuation of treatment from these drugs

20. Underlying medical conditions in investigator's opinion to be unfavorable to be a part
of the study

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/Phase 2
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)
NSW,VIC,WA
Recruitment hospital [1] 0 0
Blacktown Cancer and Haematology Centre - Blacktown
Recruitment hospital [2] 0 0
The Prince of Wales Private Hospital - Specialist Medical Randwick - Randwick
Recruitment hospital [3] 0 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment hospital [4] 0 0
Linear Clinical Research - Nedlands
Recruitment postcode(s) [1] 0 0
2148 - Blacktown
Recruitment postcode(s) [2] 0 0
2031 - Randwick
Recruitment postcode(s) [3] 0 0
3000 - Melbourne
Recruitment postcode(s) [4] 0 0
6009 - Nedlands

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
BeiGene
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
SpringWorks Therapeutics, Inc.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This is a 2-part Phase 1b study of BGB-283 (lifirafenib) and PD-0325901 combination in
patients with tumors.
Trial website
https://clinicaltrials.gov/show/NCT03905148
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
Debbie Savitescu
Address 0 0
Country 0 0
Phone 0 0
1 (877) 828-5568
Fax 0 0
Email 0 0
debbie.savitescu@beigene.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03905148