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Purpose

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.

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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

Study Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Sequential Assignment
Intervention Model Description
The study will be conducted in two sequential parts: Part 1 dose escalation (Phase 1) and Part 2 dose expansion (Phase 2a).
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Phase 1 Dose Escalation Cohorts Ranging in Dose 		Participants with an oncogenic mutation or other genomic aberration of the MAPK pathway
  • Drug: Mirdametinib
    Mirdametinib administered orally
    Other names:
    • PD-0325901
  • Drug: BGB-3245
    BGB-3245 administered orally
Experimental
Phase 2 Dose Expansion A 		Participants with cutaneous melanoma harboring NRAS mutations
  • Drug: Mirdametinib
    Mirdametinib administered orally
    Other names:
    • PD-0325901
  • Drug: BGB-3245
    BGB-3245 administered orally
Experimental
Phase 2 Dose Expansion B 		Participants with NSCLC harboring KRAS mutations
  • Drug: Mirdametinib
    Mirdametinib administered orally
    Other names:
    • PD-0325901
  • Drug: BGB-3245
    BGB-3245 administered orally
Experimental
Phase 2 Dose Expansion C 		Participants with NSCLC or cutaneous melanoma harboring BRAF Class II or Class III mutation or BRAF Fusion mutation
  • Drug: Mirdametinib
    Mirdametinib administered orally
    Other names:
    • PD-0325901
  • Drug: BGB-3245
    BGB-3245 administered orally

Recruiting Locations

Massachusetts General Hospital
Boston, Massachusetts 02114
Contact:
Ryan J Sullivan, MD
617-724-4000
RSULLIVAN7@PARTNERS.ORG

More Details

Status
Recruiting
Sponsor
SpringWorks Therapeutics, Inc.

Study Contact

SpringWorks Clinical
877-279-4870
clinical@springworkstx.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.