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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03905148
Recruitment Status : Recruiting
First Posted : April 5, 2019
Last Update Posted : March 9, 2022
Sponsor:
Collaborator:
SpringWorks Therapeutics, Inc.
Information provided by (Responsible Party):
BeiGene

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

Condition or disease Intervention/treatment Phase
Solid Tumor, Adult Drug: Lifirafenib Drug: mirdametinib Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 105 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Part A will consist of dose escalation and dose-finding components to establish the max tolerated dose and/or recommended Phase 2 dose Part B will investigate efficacy and further evaluate the PK, safety, and tolerability of the combination of PD-0325901 and BGB-283 (lifirafenib).
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : May 1, 2019
Estimated Primary Completion Date : March 30, 2024
Estimated Study Completion Date : April 29, 2024

Arm Intervention/treatment
Experimental: 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
Drug: Lifirafenib
RAF Dimer Inhibitor
Other Name: BGB-283

Drug: mirdametinib
MEK Inhibitor
Other Name: PD-0325901

Experimental: Part B: Group 1
Non-small cell lung cancer with confirmed K-RAS mutations, approximately 15 participants
Drug: Lifirafenib
RAF Dimer Inhibitor
Other Name: BGB-283

Drug: mirdametinib
MEK Inhibitor
Other Name: PD-0325901

Experimental: Part B: Group 2
Endometrial cancer with confirmed K-RAS mutations, approximately 15 participants
Drug: Lifirafenib
RAF Dimer Inhibitor
Other Name: BGB-283

Drug: mirdametinib
MEK Inhibitor
Other Name: PD-0325901

Experimental: Part B: Group 3
Tumor type of interest based on preliminary anti-tumor clinical activities observed in Part A, approximately 15 participants
Drug: Lifirafenib
RAF Dimer Inhibitor
Other Name: BGB-283

Drug: mirdametinib
MEK Inhibitor
Other Name: PD-0325901




Primary Outcome Measures :
  1. Adverse Events and Serious Adverse Events [ Time Frame: Approximately 2 years from date of the participants enrollment ]
    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

  2. The incidence of DLT events and treatment-emergent AEs (TEAEs) [ Time Frame: Approximately 2 years from date of the participants enrollment ]
  3. Objective response rate based on Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 in participants with selected tumor types [ Time Frame: Approximately 2 years from date of the participants enrollment ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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: 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. 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 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.

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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03905148


Contacts
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Contact: BeiGene 1 (877) 828-5568 clinicaltrials@beigene.com

Locations
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United States, California
University of California Los Angeles Recruiting
Santa Monica, California, United States, 90404
United States, Texas
MD Anderson Recruiting
Houston, Texas, United States, 77030
Australia, New South Wales
Blacktown Cancer and Haematology Centre Recruiting
Blacktown, New South Wales, Australia, 2148
The Prince of Wales Private Hospital - Specialist Medical Randwick Recruiting
Randwick, New South Wales, Australia, 2031
Australia, Victoria
Peter MacCallum Cancer Centre Recruiting
Melbourne, Victoria, Australia, 3000
Australia, Western Australia
Linear Clinical Research Recruiting
Nedlands, Western Australia, Australia, 6009
Sponsors and Collaborators
BeiGene
SpringWorks Therapeutics, Inc.
Publications of Results:
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Responsible Party: BeiGene
ClinicalTrials.gov Identifier: NCT03905148    
Other Study ID Numbers: BGB-283/PD-0325901-AU-001
First Posted: April 5, 2019    Key Record Dates
Last Update Posted: March 9, 2022
Last Verified: February 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
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Neoplasms