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

NCT ID: NCT03905148

Last Updated: 2026-01-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 91 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-05-01
• Study Completion Date: 2025-10-23

Brief Summary

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

Conditions

Solid Tumor, Adult

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part A: Dose Escalation/Dose finding Dose Level Cohorts ranging in dose levels and dose regimens.

Combination doses of, Mirdametinib at once a day and lifirafenib at once a day And Mirdametinib at twice a day and lifirafenib at once a day

Group Type: EXPERIMENTAL

Lifirafenib

Intervention Type: DRUG

RAF Dimer Inhibitor

mirdametinib

Intervention Type: DRUG

MEK Inhibitor

Part B: Expansion

Approximately 20 participants with NRAS mutated solid tumors will be enrolled

Group Type: EXPERIMENTAL

Lifirafenib

Intervention Type: DRUG

RAF Dimer Inhibitor

mirdametinib

Intervention Type: DRUG

MEK Inhibitor

Interventions

Lifirafenib

RAF Dimer Inhibitor

Intervention Type: DRUG

mirdametinib

MEK Inhibitor

Intervention Type: DRUG

Other Intervention Names

BGB-283; PD-0325901

Eligibility Criteria

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.

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

SpringWorks Therapeutics, Inc.

INDUSTRY

Sponsor Role: collaborator

BeiGene

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University of California Los Angeles

Santa Monica, California, United States

MD Anderson

Houston, Texas, United States

Blacktown Cancer and Haematology Centre

Blacktown, New South Wales, Australia

The Prince of Wales Private Hospital - Specialist Medical Randwick

Randwick, New South Wales, Australia

Peter MacCallum Cancer Centre

Melbourne, Victoria, Australia

Linear Clinical Research

Nedlands, Western Australia, Australia

Countries

United States; Australia

References

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, Solomon B. Phase I, Open-Label, Dose-Escalation/Dose-Expansion Study of Lifirafenib (BGB-283), an RAF Family Kinase Inhibitor, in Patients With Solid Tumors. J Clin Oncol. 2020 Jul 1;38(19):2140-2150. doi: 10.1200/JCO.19.02654. Epub 2020 Mar 17.

Reference Type: RESULT

PMID: 32182156 (View on PubMed)

Other Identifiers

BGB-283/PD-0325901-AU-001

Identifier Type: -

Identifier Source: org_study_id