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

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Status and phase

Enrolling
Phase 1

Conditions

Solid Tumor, Adult

Treatments

Drug: mirdametinib
Drug: Lifirafenib

Study type

Interventional

Funder types

Industry

Identifiers

NCT03905148
BGB-283/PD-0325901-AU-001

Details and patient eligibility

About

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

Enrollment

105 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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: 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.
  • 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 of the signing of 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.

Trial design

105 participants in 2 patient groups

Part A: Dose Escalation/Dose finding Dose Level Cohorts ranging in dose levels and dose regimens.
Experimental group
Description:
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
Treatment:
Drug: mirdametinib
Drug: Lifirafenib
Part B: Expansion
Experimental group
Description:
Approximately 20 participants with NRAS mutated solid tumors will be enrolled
Treatment:
Drug: mirdametinib
Drug: Lifirafenib

Trial contacts and locations

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Central trial contact

BeiGene

Data sourced from clinicaltrials.gov

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