Description:
This is a 2-part Phase 1b study of BGB-283 (lifirafenib) and PD-0325901 (mirdametinib) combination in participants with tumors.
This is a 2-part Phase 1b study of BGB-283 (lifirafenib) and PD-0325901 (mirdametinib) combination in participants with tumors.
Recruiting
Phase 1/Phase 2
Drug | Synonyms | Arms |
---|---|---|
Lifirafenib | BGB-283 | Part A: Dose Level 1 |
mirdametinib | PD-0325901 | Part A: Dose Level 1 |
Name | Type | Description | Interventions |
---|---|---|---|
Part A: Dose Level 1 | Experimental | Mirdametinib at 2 mg once a day and lifirafenib at 15 mg once a day |
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Part A: Dose Level 2 | Experimental | Mirdametinib at 2 mg once a day and lifirafenib at 20 mg once a day |
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Part A: Dose Level 3 | Experimental | Mirdametinib at 4 mg once a day and lifirafenib at 20 mg once a day |
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Part A: Dose Level 4 | Experimental | Mirdametinib 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 |
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Part B: Group 1 | Experimental | Non-small cell lung cancer with confirmed K-RAS mutations, approximately 15 participants |
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Part B: Group 2 | Experimental | Endometrial cancer with confirmed K-RAS mutations, approximately 15 participants |
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Part B: Group 3 | Experimental | Tumor type of interest based on preliminary anti-tumor clinical activities observed in Part A, approximately 15 participants |
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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 |
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 |
Phase: | Phase 1/Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | BeiGene |
September 28, 2020