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

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

Study Overview

• Status: Recruiting
• Conditions: Solid Tumor, Adult
• Intervention / Treatment: Drug: Lifirafenib; Drug: mirdametinib

• Study Type: Interventional
• Enrollment (Estimated): 105
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: BeiGene; Phone Number: 1 (877) 828-5568; Email: clinicaltrials@beigene.com

Study Locations

• Australia
  • New South Wales
    • Blacktown, New South Wales, Australia, 2148
      • Recruiting
      • Blacktown Cancer and Haematology Centre
    • Randwick, New South Wales, Australia, 2031
      • Recruiting
      • The Prince of Wales Private Hospital - Specialist Medical Randwick
  • Victoria
    • Melbourne, Victoria, Australia, 3000
      • Recruiting
      • Peter MacCallum Cancer Centre
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Recruiting
      • Linear Clinical Research
• United States
  • California
    • Santa Monica, California, United States, 90404
      • Recruiting
      • University of California Los Angeles
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • MD Anderson

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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: 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.
4. Must have archival tumor tissue or agree to tumor biopsy
5. Measurable disease per RECIST 1.1
6. Eastern Cooperative Oncology Group performance status of less than or equal to 1
7. Life expectancy is greater than 12 weeks of the signing of 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. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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: Expansion; Approximately 20 participants with NRAS mutated solid tumors will be enrolled	Drug: Lifirafenib; RAF Dimer Inhibitor; Other Names: BGB-283; Drug: mirdametinib; MEK Inhibitor; Other Names: PD-0325901

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events and Serious Adverse Events	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	Approximately 2 years from date of the participants enrollment
The incidence of DLT events and treatment-emergent AEs (TEAEs)		Approximately 2 years from date of the participants enrollment
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

Collaborators and Investigators

• Sponsor: BeiGene
• Collaborators: SpringWorks Therapeutics, Inc.

Publications and helpful links

General Publications

• Desai J, Gan H, Barrow C, Jameson M, Atkinson V, Haydon A, Millward M, Begbie S, Brown M, Markman B, Patterson W, Hill A, Horvath L, Nagrial A, Richardson G, Jackson C, Friedlander M, Parente P, Tran B, Wang L, Chen Y, Tang Z, Huang W, Wu J, Zeng D, Luo L, Solomon B. Phase I, Open-Label, Dose-Escalation/Dose-Expansion Study of Lifirafenib (BGB-283), an RAF Family Kinase Inhibitor, in Patients With Solid Tumors. J Clin Oncol. 2020 Jul 1;38(19):2140-2150. doi: 10.1200/JCO.19.02654. Epub 2020 Mar 17.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2019
• Primary Completion (Estimated): September 30, 2025
• Study Completion (Estimated): February 28, 2026

Study Registration Dates

• First Submitted: April 3, 2019
• First Submitted That Met QC Criteria: April 4, 2019
• First Posted (Actual): April 5, 2019

Study Record Updates

• Last Update Posted (Actual): June 6, 2023
• Last Update Submitted That Met QC Criteria: June 5, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: BGB-283/PD-0325901-AU-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• 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