The purpose of this study is to find out whether mirdametinib in combination with palbociclib is an effective and safe treatment for people with metastatic, recurrent, and unresectable liposarcoma. This study will test different doses of mirdametinib in combination with a fixed dose of palbociclib to find the best safe dose for further testing.
A diagnosis of unresectable, recurrent, or metastatic DDLPS
Measurable disease as defined by RECIST 1.1
A diagnosis of unresectable, recurrent (e.g. recurrent retroperitoneal) or metastatic DDLPS
Any number of prior lines of therapy
Patients who have not recovered from clinically significant adverse events of prior therapy to ≤ NCI CTCAE v5 Grade 1, except alopecia and stable neuropathy, which must have resolved to ≤ Grade 2 or baseline.
Patients receiving any other investigational agents.
Phase II only: Receipt of prior treatment with a selective CDK4 inhibitor or MEK inhibitor
Uncontrolled intercurrent illness including, but not limited to, known ongoing or active infection, including uncontrolled HIV, active hepatitis B or C, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmias, psychiatric illness/social situations that would limit compliance with study requirements, clinically significant interstitial lung disease or active noninfectious pneumonitis, or active infection requiring systemic therapy.
Sequential
Mirdametinib
DrugMirdametinib (PD-0325901) is a highly selective non-ATP-competitive inhibitor of MEK1 and MEK2. It significantly inhibits the phosphorylation of the MAP kinases ERK1 and ERK2, leading to impaired tumor cell growth in vitro and in vivo in a broad spectrum of human tumors
Palbociclib
DrugPalbociclib (IBRANCE®) is a kinase inhibitor FDA approved for the following indications: treatment of adults with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer in combination with an aromatase inhibitor as initial endocrine-based therapy in postmenopausal women or in men or fulvestrant in patients with disease progression following endocrine therapy.
Maximum tolerated dose (Phase I)
To determine the recommended phase 2 dose (RP2D) of mirdametinib plus palbociclib in patients with DDLPS
Progression free survival rate
Phase II: To determine the progression-free survival rate at 18 weeks by RECIST 1.1
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Memorial Sloan Kettering Cancer Center
Lead sponsor
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Collaborator
