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

Sponsor
BeiGene (Industry)
Overall Status
Recruiting
CT.gov ID
NCT03905148
Collaborator
SpringWorks Therapeutics, Inc. (Industry)
105
6
4
60
17.5
0.3

Study Details

Study Description

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
Phase 1/Phase 2

Study Design

Study Type:
Interventional
Anticipated 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).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
Anticipated Primary Completion Date :
Mar 30, 2024
Anticipated Study Completion Date :
Apr 29, 2024

Arms and Interventions

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 Names:
  • BGB-283
  • Drug: mirdametinib
    MEK Inhibitor
    Other Names:
  • 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 Names:
  • BGB-283
  • Drug: mirdametinib
    MEK Inhibitor
    Other Names:
  • PD-0325901
  • Experimental: Part B: Group 2

    Endometrial cancer with confirmed K-RAS mutations, approximately 15 participants

    Drug: Lifirafenib
    RAF Dimer Inhibitor
    Other Names:
  • BGB-283
  • Drug: mirdametinib
    MEK Inhibitor
    Other Names:
  • 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 Names:
  • BGB-283
  • Drug: mirdametinib
    MEK Inhibitor
    Other Names:
  • PD-0325901
  • Outcome Measures

    Primary Outcome Measures

    1. Adverse Events and Serious Adverse Events [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) [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 [Approximately 2 years from date of the participants enrollment]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

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

    2. Measurable disease per RECIST 1.1

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

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

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

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

    7. 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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of California Los Angeles Santa Monica California United States 90404
    2 MD Anderson Houston Texas United States 77030
    3 Blacktown Cancer and Haematology Centre Blacktown New South Wales Australia 2148
    4 The Prince of Wales Private Hospital - Specialist Medical Randwick Randwick New South Wales Australia 2031
    5 Peter MacCallum Cancer Centre Melbourne Victoria Australia 3000
    6 Linear Clinical Research Nedlands Western Australia Australia 6009

    Sponsors and Collaborators

    • BeiGene
    • SpringWorks Therapeutics, Inc.

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    BeiGene
    ClinicalTrials.gov Identifier:
    NCT03905148
    Other Study ID Numbers:
    • BGB-283/PD-0325901-AU-001
    First Posted:
    Apr 5, 2019
    Last Update Posted:
    Mar 9, 2022
    Last Verified:
    Feb 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    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:

    Study Results

    No Results Posted as of Mar 9, 2022