Clinical trial NCT05580770: Mirdametinib + BGB-3245 in Advanced Solid Tumors
Official title: A Phase 1/2a Open-Label, Dose Escalation and Expansion Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics and Efficacy of Mirdametinib in Combination With BGB-3245 in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Advanced Solid Tumor
Lead sponsor: SpringWorks Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2022-10-14
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
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

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.


Eligibility criteria: Key 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

Key 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

Primary outcomes:
measure: Incidence of treatment emergent adverse events
timeFrame: Up to 24 months
measure: Maximum Tolerated Dose (Part 1 Only)
timeFrame: Up to 18 months
measure: Recommended Phase 2 Dose (Part 1 Only)
timeFrame: Up to 24 months
measure: Objective Response Rate (Part 2 Only)
timeFrame: Up to 24 months
Secondary outcomes:
measure: Objective Response Rate (Part 1 Only)
timeFrame: Up to 24 months
measure: Duration of Response Rate
timeFrame: Up to 36 months
measure: Change in plasma concentrations of mirdametinib and BGB-3245
timeFrame: Up to 24 months
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: UC San Diego Moores Cancer Center
state: California
city: New Haven
country: United States
facility: Yale-New Haven Hospital-Yale Cancer Center
state: Connecticut
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Dallas
country: United States
facility: Texas Oncology-Baylor Charles A. Sammons Cancer Center
state: Texas
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Waratah
country: Australia
facility: Calvary Mater Newcastle
Study officials:
References: