Clinical Trials /

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

NCT03905148

Description:

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

Related Conditions:
  • Endometrial Carcinoma
  • Malignant Solid Tumor
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of the Safety and Pharmacokinetics of BGB-283 (Lifirfenib) and PD-0325901 (Mirdametinib) in Participants With Advanced or Refractory Solid Tumors
  • 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

Clinical Trial IDs

  • ORG STUDY ID: BGB-283/PD-0325901-AU-001
  • NCT ID: NCT03905148

Conditions

  • Solid Tumor, Adult

Interventions

DrugSynonymsArms
LifirafenibBGB-283Part A: Dose Level 1
mirdametinibPD-0325901Part A: Dose Level 1

Purpose

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

Trial Arms

NameTypeDescriptionInterventions
Part A: Dose Level 1ExperimentalMirdametinib at 2 mg once a day and lifirafenib at 15 mg once a day
  • Lifirafenib
  • mirdametinib
Part A: Dose Level 2ExperimentalMirdametinib at 2 mg once a day and lifirafenib at 20 mg once a day
  • Lifirafenib
  • mirdametinib
Part A: Dose Level 3ExperimentalMirdametinib at 4 mg once a day and lifirafenib at 20 mg once a day
  • Lifirafenib
  • mirdametinib
Part A: Dose Level 4ExperimentalMirdametinib at 6 or 8 mg once a day and lifirafenib at 20 or 25 mg once a day depending on the safety and tolerability observed at Levels 1, 2, and 3
  • Lifirafenib
  • mirdametinib
Part B: Group 1ExperimentalNon-small cell lung cancer with confirmed K-RAS mutations, approximately 15 participants
  • Lifirafenib
  • mirdametinib
Part B: Group 2ExperimentalEndometrial cancer with confirmed K-RAS mutations, approximately 15 participants
  • Lifirafenib
  • mirdametinib
Part B: Group 3ExperimentalTumor type of interest based on preliminary anti-tumor clinical activities observed in Part A, approximately 15 participants
  • Lifirafenib
  • mirdametinib

Eligibility 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 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. Measureable disease per RECIST 1.1

          6. Eastern Cooperative Oncology Group performance status of greater than 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. Increased serum calcium

         13. Inability to swallow oral medications

         14. Ongoing radiation therapy or radio-cytotoxic therapy within prior 4 weeks. No
             immunotherapy,biologic therapy, hormonal, or molecular targeted therapy within prior 2
             weeks

         15. Concomitant systemic or glucocorticoid therapy

         16. Concomitant vitamin D

         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 significant 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

        NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Adverse Events and Serious Adverse Events
Time Frame:Approximately 2 years from date of the participants enrollment
Safety Issue:
Description: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 4.03

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:BeiGene

Last Updated

September 28, 2020