Mirdametinib + BGB-3245 in Advanced Solid Tumors

NCT ID: NCT05580770

Last Updated: 2025-02-17

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-02-03
• Study Completion Date: 2025-01-15

Brief Summary

A Phase 1/2a open-label, multicenter, dose escalation and expansion study of mirdametinib in combination with BGB-3245 in adult participants with histologically confirmed, advanced (American Joint Committee on Cancer (AJCC) Stage III or IV) metastatic or unresectable solid cancer that is refractory to or has progressed during or after at least 1 line of appropriate prior systemic anti-cancer therapy including chemotherapy, immunotherapy, or appropriate targeted therapy, or for which there is no treatment available, or prior standard of care therapy was not tolerated.

Conditions

Advanced Solid Tumor

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase 1 Dose Escalation Cohorts Ranging in Dose

Participants with an oncogenic mutation or other genomic aberration of the MAPK pathway

Group Type: EXPERIMENTAL

Mirdametinib

Intervention Type: DRUG

Mirdametinib administered orally

BGB-3245

Intervention Type: DRUG

BGB-3245 administered orally

Phase 2 Dose Expansion A

Participants with cutaneous melanoma harboring NRAS mutations

Group Type: EXPERIMENTAL

Mirdametinib

Intervention Type: DRUG

Mirdametinib administered orally

BGB-3245

Intervention Type: DRUG

BGB-3245 administered orally

Phase 2 Dose Expansion B

Participants with NSCLC harboring KRAS mutations

Group Type: EXPERIMENTAL

Mirdametinib

Intervention Type: DRUG

Mirdametinib administered orally

BGB-3245

Intervention Type: DRUG

BGB-3245 administered orally

Phase 2 Dose Expansion C

Participants with NSCLC or cutaneous melanoma harboring BRAF Class II or Class III mutation or BRAF Fusion mutation

Group Type: EXPERIMENTAL

Mirdametinib

Intervention Type: DRUG

Mirdametinib administered orally

BGB-3245

Intervention Type: DRUG

BGB-3245 administered orally

Interventions

Mirdametinib

Mirdametinib administered orally

Intervention Type: DRUG

BGB-3245

BGB-3245 administered orally

Intervention Type: DRUG

Other Intervention Names

PD-0325901

Eligibility Criteria

Inclusion Criteria

• Able to provide informed consent
• At least 18 years of age on day of signing ICF
• Advanced, metastatic or unresectable solid cancer that has not responded to or progressed during or after at least 1 line of appropriate therapy or for which there is no treatment available or prior therapy was not tolerated.
• Part 1: oncogenic mutation or other genomic aberration of the MAPK pathway
• Part 2: oncogenic mutation or genomic aberration defined below:

• Cohort A: cutaneous melanoma harboring NRAS mutations.
• Cohort B: non-small cell lung cancer (NSCLC) harboring a KRAS mutation.
• Cohort C: NSCLC or cutaneous melanoma harboring BRAF Class II or Class III mutations or BRAF Fusion mutation.
• Must have archival tumor tissue or agree to a fresh tumor biopsy at screening
• Measurable disease per RECIST 1.1
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
• Adequate organ function and no transfusion within 14 days of first dose

Exclusion Criteria

• Central Nervous System metastases, leptomeningeal carcinomatosis or untreated spinal cord compression
• History of glaucoma
• Active parathyroid disorder or history of malignancy associated hypercalcemia
• Clinically significant cardiac disease within the past 6 months of signing ICF
• History of toxicity from another RAF, MEK, ERK inhibitor requiring discontinuation of treatment from these agents
• Severe or uncontrolled systemic disease
• Inability to swallow oral medications
• Clinically significant active infection (HIV, Hepatitis B or Hepatitis C)
• History of or ongoing Immune Thrombocytopenia (ITP), Von Willebrand disease and/or other past or present bleeding disorders
• Underlying medical conditions in investigator's opinion to be unfavorable to be a part of the study
• Major surgical procedure or significant traumatic injury within 4 weeks prior to first dose or anticipates need for major surgery while on study
• Systemic anti-cancer therapy within 2 weeks or 5 half-lives before first dose
• Concomitant systemic or glucocorticoid therapy within 2 weeks before first dose
• Concomitant medicines that are strong CYP3A4 inhibitors or inducers within 2 weeks or 5 half-lives before first dose
• Live vaccine within 4 weeks before first dose

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

SpringWorks Therapeutics, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

UC San Diego Moores Cancer Center

La Jolla, California, United States

Yale-New Haven Hospital-Yale Cancer Center

New Haven, Connecticut, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

University Hospitals Cleveland Medical Center

Cleveland, Ohio, United States

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Texas Oncology-Baylor Charles A. Sammons Cancer Center

Dallas, Texas, United States

Peter MacCallum Cancer Centre

Melbourne, Victoria, Australia

Calvary Mater Newcastle

Waratah, , Australia

Countries

United States; Australia

Other Identifiers

MEKRAF-AST-101

Identifier Type: -

Identifier Source: org_study_id