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Study of the Safety and Pharmacokinetics of BGB-283 and PD-0325901 in Patients With Advanced or Refractory Solid Tumors

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ClinicalTrials.gov Identifier: NCT03905148
Recruitment Status : Recruiting
First Posted : April 5, 2019
Last Update Posted : September 11, 2019
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 combination in patients with tumors.

Condition or disease Intervention/treatment Phase
Solid Tumor, Adult Drug: BGB-283 (lifirafenib) Drug: PD-0325901 Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 75 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 : February 1, 2022
Estimated Study Completion Date : March 1, 2022

Arm Intervention/treatment
Experimental: Part A: Dose Level 1
PD-0325901 at 2 mg once a day and BGB-283 (lifirafenib) at 15 mg once a day
Drug: BGB-283 (lifirafenib)
RAF Dimer Inhibitor

Drug: PD-0325901
MEK Inhibitor

Experimental: Part A: Dose Level 2
PD-0325901 at 2 mg once a day and BGB-283 (lifirafenib) at 20 mg once a day
Drug: BGB-283 (lifirafenib)
RAF Dimer Inhibitor

Drug: PD-0325901
MEK Inhibitor

Experimental: Part A: Dose Level 3
PD-0325901 at 4 mg once a day and BGB-283 (lifirafenib) at 20 mg once a day
Drug: BGB-283 (lifirafenib)
RAF Dimer Inhibitor

Drug: PD-0325901
MEK Inhibitor

Experimental: Part A: Dose Level 4
PD-0325901 at 6 or 8 mg once a day and BGB-283 (lifirafenib) at 20 or 25 mg once a day depending on the safety and tolerability observed at Levels 1, 2, and 3
Drug: BGB-283 (lifirafenib)
RAF Dimer Inhibitor

Drug: PD-0325901
MEK Inhibitor

Experimental: Part B: Group 1
Non-small cell lung cancer with confirmed K-RAS mutations, approximately 15 patients
Drug: BGB-283 (lifirafenib)
RAF Dimer Inhibitor

Drug: PD-0325901
MEK Inhibitor

Experimental: Part B: Group 2
Endometrial cancer with confirmed K-RAS mutations, approximately 15 patients
Drug: BGB-283 (lifirafenib)
RAF Dimer Inhibitor

Drug: PD-0325901
MEK Inhibitor

Experimental: Part B: Group 3
Tumor type of interest based on preliminary anti-tumor clinical activities observed in Part A, approximately 15 patients
Drug: BGB-283 (lifirafenib)
RAF Dimer Inhibitor

Drug: PD-0325901
MEK Inhibitor




Primary Outcome Measures :
  1. Adverse Events and Serious Adverse Events [ Time Frame: Approximately 2 years from date of the patient 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 4.03

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

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.

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 v4.03 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

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: Debbie Savitescu 1 (877) 828-5568 debbie.savitescu@beigene.com
Contact: Margaret Singh 1 (877) 828-5568 clinicaltrials@beigene.com

Locations
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Australia, New South Wales
Blacktown Cancer and Haematology Centre Recruiting
Blacktown, New South Wales, Australia, 2148
Principal Investigator: Bo Gao         
The Prince of Wales Private Hospital - Specialist Medical Randwick Recruiting
Randwick, New South Wales, Australia, 2031
Principal Investigator: Michael Friedlander         
Australia, Victoria
Peter MacCallum Cancer Centre Recruiting
Melbourne, Victoria, Australia, 3000
Principal Investigator: Benjamin Solomon         
Australia, Western Australia
Linear Clinical Research Recruiting
Nedlands, Western Australia, Australia, 6009
Principal Investigator: Michael Millward         
Sponsors and Collaborators
BeiGene
SpringWorks Therapeutics, Inc.

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Responsible Party: BeiGene
ClinicalTrials.gov Identifier: NCT03905148     History of Changes
Other Study ID Numbers: BGB-283/PD-0325901-AU-001
First Posted: April 5, 2019    Key Record Dates
Last Update Posted: September 11, 2019
Last Verified: September 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Neoplasms