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

Phase 1

Active, not recruiting

• Conditions: Solid Tumor, Adult
• Interventions: Drug: Lifirafenib; Drug: mirdametinib

• Registration Number: NCT03905148
• Lead Sponsor: BeiGene

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-04-03
• Study First Submitted QC: 2019-04-04
• Study First Posted: 2019-04-05
• Study Start: 2019-05-01
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-13
• Last Update Posted: 2025-03-14
• Primary Completion: 2025-09-30
• Study Completion: 2026-02-28

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 93

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Part A: Dose Escalation/Dose finding Dose Level Cohorts ranging in dose levels and dose regimens.	Lifirafenib	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
Part A: Dose Escalation/Dose finding Dose Level Cohorts ranging in dose levels and dose regimens.	mirdametinib	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
Part B: Expansion	mirdametinib	Approximately 20 participants with NRAS mutated solid tumors will be enrolled
Part B: Expansion	Lifirafenib	Approximately 20 participants with NRAS mutated solid tumors will be enrolled

Primary Outcome Measures

Name	Time	Method
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
The incidence of DLT events and treatment-emergent AEs (TEAEs)	Approximately 2 years from date of the participants enrollment
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

Trial Locations

Locations (6)

University of California Los Angeles; 🇺🇸 Santa Monica, California, United States

MD Anderson; 🇺🇸 Houston, Texas, United States

Blacktown Cancer and Haematology Centre; 🇦🇺 Blacktown, New South Wales, Australia

The Prince of Wales Private Hospital - Specialist Medical Randwick; 🇦🇺 Randwick, New South Wales, Australia

Peter MacCallum Cancer Centre; 🇦🇺 Melbourne, Victoria, Australia

Linear Clinical Research; 🇦🇺 Nedlands, Western Australia, Australia