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

NCT03905148 | Completed Phase 1 FDA Drug

• 1 other identifier: BGB-283/PD-0325901-AU-001
• Study Type: interventional
• Target: 91
• Locations: 2 countries
• Sites: 6

Brief Summary

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

Conditions

Solid Tumor, Adult

Outcome Measures

Primary Outcomes (3)

• 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

Study Arms (2)

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

Drug: Lifirafenib; Drug: mirdametinib

Part B: Expansion

EXPERIMENTAL

Approximately 20 participants with NRAS mutated solid tumors will be enrolled

Drug: Lifirafenib; Drug: mirdametinib

Interventions

Lifirafenib DRUG

RAF Dimer Inhibitor

Also known as: BGB-283

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

mirdametinib DRUG

MEK Inhibitor

Also known as: PD-0325901

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• BeiGene: lead
• SpringWorks Therapeutics, Inc.: collaborator

Study Sites (6)

University of California Los Angeles

Santa Monica, California, 90404, United States

Location

MD Anderson

Houston, Texas, 77030, United States

Location

Blacktown Cancer and Haematology Centre

Blacktown, New South Wales, 2148, Australia

Location

The Prince of Wales Private Hospital - Specialist Medical Randwick

Randwick, New South Wales, 2031, Australia

Location

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

Location

Linear Clinical Research

Nedlands, Western Australia, 6009, Australia

Location

Related Publications (1)

• 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.

  PMID: 32182156 RESULT

MeSH Terms

Interventions

BGB-283; mirdametinib

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: April 3, 2019
• First Posted: April 5, 2019
• Study Start: May 1, 2019
• Primary Completion: October 9, 2024
• Study Completion: October 23, 2025
• Last Updated: January 7, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share

Locations

US (2); AU (4)