Study of the Safety and Pharmacokinetics of BGB-283 (Lifirafenib) and PD-0325901 (Mirdametinib) in Participants With Advanced or Refractory Solid Tumors
Study Details
Study Description
Brief Summary
This is a 2-part Phase 1b study of BGB-283 (lifirafenib) and PD-0325901 (mirdametinib) combination in participants with tumors.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 1/Phase 2 |
Study Design
Arms and Interventions
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:
Drug: mirdametinib
MEK Inhibitor
Other Names:
|
Experimental: Part B: Group 1 Non-small cell lung cancer with confirmed K-RAS mutations, approximately 15 participants |
Drug: Lifirafenib
RAF Dimer Inhibitor
Other Names:
Drug: mirdametinib
MEK Inhibitor
Other Names:
|
Experimental: Part B: Group 2 Endometrial cancer with confirmed K-RAS mutations, approximately 15 participants |
Drug: Lifirafenib
RAF Dimer Inhibitor
Other Names:
Drug: mirdametinib
MEK Inhibitor
Other Names:
|
Experimental: Part B: Group 3 Tumor type of interest based on preliminary anti-tumor clinical activities observed in Part A, approximately 15 participants |
Drug: Lifirafenib
RAF Dimer Inhibitor
Other Names:
Drug: mirdametinib
MEK Inhibitor
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Adverse Events and Serious Adverse Events [Approximately 2 years from date of the participants 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 5.0
- 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]
Eligibility Criteria
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
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Part A: NSCLC, CRC, ovarian cancer, endometrial cancer, thyroid cancer, melanoma, pancreatic cancer, and other)
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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
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Must have archival tumor tissue or agree to tumor biopsy
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Measurable disease per RECIST 1.1
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Eastern Cooperative Oncology Group performance status of less than or equal to 1
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Life expectancy is greater than 12 weeks at the of signing ICF.
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Adequate organ function and no transfusion within 14 days of first dose.
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Females are of non-child bearing potential or willing to use contraception.
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Males vasectomized or agree to use contraception.
Key Exclusion Criteria:
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Central Nervous System metastasis
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Any retinal pathology considered to be a risk factor for central serous retinopathy
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History of glaucoma
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Active parathyroid disorder or history of malignancy associated hypercalcemia
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Clinically significant cardiac disease within the past 6 months of signing ICF.
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LVEF less than 50%
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Abnormal QT interval at Screening
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Severe uncontrolled systemic disease
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HIV
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Clinically significant active or known history of liver disease. (Hepatitis B and Hepatitis C)
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Hemorrhage or bleeding event at NCI-CTCAE v5.0 Grade 3 or higher within 28 days of first dose.
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history of or ongoing Von Willebrand disease and/or other past or present bleeding disorders
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Increased serum calcium
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Inability to swallow oral medications
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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
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Concomitant systemic or glucocorticoid therapy within 2 weeks
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Major surgical procedure or significant traumatic injury within 4 weeks prior to first dose or anticipates need for major surgery while on study
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Concomitant medicines that are strong CYP3A inhibitors
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History of toxicity from another RAF, MEK, ERK inhibitor requiring discontinuation of treatment from these drugs
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Underlying medical conditions in investigator's opinion to be unfavorable to be a part of the study
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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.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | University of California Los Angeles | Santa Monica | California | United States | 90404 |
2 | MD Anderson | Houston | Texas | United States | 77030 |
3 | Blacktown Cancer and Haematology Centre | Blacktown | New South Wales | Australia | 2148 |
4 | The Prince of Wales Private Hospital - Specialist Medical Randwick | Randwick | New South Wales | Australia | 2031 |
5 | Peter MacCallum Cancer Centre | Melbourne | Victoria | Australia | 3000 |
6 | Linear Clinical Research | Nedlands | Western Australia | Australia | 6009 |
Sponsors and Collaborators
- BeiGene
- SpringWorks Therapeutics, Inc.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- BGB-283/PD-0325901-AU-001