Study of the Safety and Pharmacokinetics of BGB-283 (Lifirafenib) and PD-0325901 (Mirdametinib) in Participants With Advanced or Refractory Solid Tumors

Solid Tumor, Adult Clinical Trial

Official 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03905148
• Other study ID #: BGB-283/PD-0325901-AU-001
• Status: Recruiting
• Phase: Phase 1
• Start date: May 1, 2019
• Est. completion date: February 28, 2026

Study information

• Verified date: June 2023
• Source: BeiGene
• Contact: BeiGene
• Phone: 1 (877) 828-5568
• Email: clinicaltrials[@]beigene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a 2-part Phase 1b study of BGB-283 (lifirafenib) and PD-0325901 (mirdametinib) combination in participants with tumors.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 105
• Est. completion date: February 28, 2026
• Est. primary completion date: September 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

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 (other than patients with tumors of the brain or central nervous system) who have experienced disease progression

• Part A: NSCLC, CRC, ovarian cancer, endometrial cancer, thyroid cancer, melanoma, pancreatic cancer, and other)
• Part B: NRAS mutated solid tumors must have a known mutation status and a histologically or cytologically confirmed advanced or refractory solid tumor. Up to 40% Melanoma and Up to 20% CRC.

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

5. Measurable disease per RECIST 1.1

6. Eastern Cooperative Oncology Group performance status of less than or equal to 1

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

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 v5.0 Grade 3 or higher within 28 days of first dose.

12. history of or ongoing Von Willebrand disease and/or other past or present bleeding disorders

13. Increased serum calcium

14. Inability to swallow oral medications

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

16. Concomitant systemic or glucocorticoid therapy within 2 weeks

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 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

21. Has been administered a live vaccine within 4 weeks (28 days) of initiation of study treatment. NOTE: injectable seasonal vaccines for influenza and COVID-19 are generally inactivated vaccines and are allowed. Intranasal vaccines are live vaccines and are not allowed. NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Related Conditions & MeSH terms

• Neoplasms
• Solid Tumor, Adult

Intervention

Drug:
• Lifirafenib
RAF Dimer Inhibitor
• mirdametinib
MEK Inhibitor

Locations

Country	Name	City	State
Australia	Blacktown Cancer and Haematology Centre	Blacktown	New South Wales
Australia	Peter MacCallum Cancer Centre	Melbourne	Victoria
Australia	Linear Clinical Research	Nedlands	Western Australia
Australia	The Prince of Wales Private Hospital - Specialist Medical Randwick	Randwick	New South Wales
United States	MD Anderson	Houston	Texas
United States	University of California Los Angeles	Santa Monica	California

Sponsors (2)

Lead Sponsor	Collaborator
BeiGene	SpringWorks Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  Australia, 

References & Publications (1)

Desai J, Gan H, Barrow C, Jameson M, Atkinson V, Haydon A, Millward M, Begbie S, Brown M, Markman B, Patterson W, Hill A, Horvath L, Nagrial A, Richardson G, Jackson C, Friedlander M, Parente P, Tran B, Wang L, Chen Y, Tang Z, Huang W, Wu J, Zeng D, Luo L — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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 5.0	Approximately 2 years from date of the participants enrollment
Primary	The incidence of DLT events and treatment-emergent AEs (TEAEs)		Approximately 2 years from date of the participants enrollment
Primary	Objective response rate based on Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 in participants with selected tumor types		Approximately 2 years from date of the participants enrollment