Title

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

    Phase 1/Phase 2
  • Study Type

    Interventional
  • Status

    Recruiting
  • Study Participants

    105
This is a 2-part Phase 1b study of BGB-283 (lifirafenib) and PD-0325901 (mirdametinib) combination in participants with tumors.
Study Started
May 01
2019
Primary Completion
Mar 30
2024
Anticipated
Study Completion
Apr 29
2024
Anticipated
Last Update
Mar 09
2022

Drug Lifirafenib

RAF Dimer Inhibitor

  • Other names: BGB-283

Drug mirdametinib

MEK Inhibitor

  • Other names: PD-0325901

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

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

Part B: Group 1 Experimental

Non-small cell lung cancer with confirmed K-RAS mutations, approximately 15 participants

Part B: Group 2 Experimental

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

Part B: Group 3 Experimental

Tumor type of interest based on preliminary anti-tumor clinical activities observed in Part A, approximately 15 participants

Criteria

Key Inclusion Criteria:

Able to provide informed consent
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

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
Must have archival tumor tissue or agree to tumor biopsy
Measurable disease per RECIST 1.1
Eastern Cooperative Oncology Group performance status of less than or equal to 1
Life expectancy is greater than 12 weeks at the of signing ICF.
Adequate organ function and no transfusion within 14 days of first dose.
Females are of non-child bearing potential or willing to use contraception.
Males vasectomized or agree to use contraception.

Key Exclusion Criteria:

Central Nervous System metastasis
Any retinal pathology considered to be a risk factor for central serous retinopathy
History of glaucoma
Active parathyroid disorder or history of malignancy associated hypercalcemia
Clinically significant cardiac disease within the past 6 months of signing ICF.
LVEF less than 50%
Abnormal QT interval at Screening
Severe uncontrolled systemic disease
HIV
Clinically significant active or known history of liver disease. (Hepatitis B and Hepatitis C)
Hemorrhage or bleeding event at NCI-CTCAE v5.0 Grade 3 or higher within 28 days of first dose.
history of or ongoing Von Willebrand disease and/or other past or present bleeding disorders
Increased serum calcium
Inability to swallow oral medications
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
Concomitant systemic or glucocorticoid therapy within 2 weeks
Major surgical procedure or significant traumatic injury within 4 weeks prior to first dose or anticipates need for major surgery while on study
Concomitant medicines that are strong CYP3A inhibitors
History of toxicity from another RAF, MEK, ERK inhibitor requiring discontinuation of treatment from these drugs
Underlying medical conditions in investigator's opinion to be unfavorable to be a part of the study
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.
No Results Posted