A Study of Mirdametinib on Its Own or in Combination With Fulvestrant in People With Solid Tumor Cancer

Completed · Phase 1/Phase 2

Conditions studied: Breast Cancer, Breast Cancer Stage IV, HER2-negative Breast Cancer, Solid Carcinoma, MEK1 Gene Mutation, MEK2 Gene Mutation, Metastatic Breast Cancer

In brief

The purpose of this study to find out whether mirdametinib is a safe treatment for people with advanced solid tumor cancer that has certain mutations. Researchers will look at whether mirdametinib on its own or in combination with the drug fulvestrant is a safe treatment that causes few or mild side effects in people with advanced solid tumor cancer.

Key facts

Study ID

NCT05054374

Run by

Memorial Sloan Kettering Cancer Center

People needed

6

Starts

2021-09-14

Expected to finish

2023-10-26

Last updated by the study team

2025-05-23

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Subjects are eligible to start the treatment in the study only if all of the following criteria apply:
• Arm 1 (metastatic breast cancer):
• Female adults (≥18 years of age on the date of informed consent)
• Postmenopausal or receiving ovarian suppression (including GnRH agonists such as goserelin)
• Histologically confirmed hormone receptor-positive metastatic breast cancer with evidence of progression on at least 1 prior line of therapy for metastatic disease which should have included a CDK4/6 inhibitor in combination with endocrine therapy. Prior chemotherapy is permitted.
• ER+ as defined by immunohistochemistry (IHC) ≥1% by local laboratory testing (as per the ASCO-CAP guidelines)
• HER2-negative, as defined by the negative in situ hybridization test (FISH, CISH, or SISH) or an IHC status of 0, 1+ or 2+ by local laboratory testing. If IHC is 2+ (i.e.
• indeterminate), then a negative in situ hybridization test (FISH, CISH, or SISH) is required (as per the ASCO-CAP guidelines).
• NF1 loss of function or another MAPK-activating genomic alteration documented by a CLIA-certified NGS assay at any time before the start of treatment. Note: archival tissue, if available and collected within 6 months of enrollment, may be used for this testing in lieu of fresh tissue.
• Arm 2 (advanced solid cancers):
• Male or female adults (≥18 years of age on the date of informed consent)
• Histologically confirmed advanced, metastatic solid tumor cancer for which there is no available therapy known to confer clinical benefit. Colorectal, anal, small bowel, biliary or ampullary cancers are not eligible.
• Class 1 or class 2 MEK1 or MEK2 mutations, as described below, documented by a CLIA-certified NGS assay at any time before the start of treatment. Class 3 MEK1 or MEK2 mutations as described in that paper are excluded. A complete list of the mutations allowed based on that paper can be found below, however, rare mutations not listed in this table may be permitted at the discretion of the principal investigator of the study. Note: archival tissue, if available and collected within 6 months of enrollment, may be used for this testing in lieu of fresh tissue.
• Class 1 - Permitted: MEK1 D67N, MEK1 P124L, MEK1 P124S Class 2 - Permitted: MEK1 K57N, MEK1 C121S, MEK1 F53L, MEK1 Q56P Class 3 - Excluded: MEK1 L98-I103, MEK1 I99-K104, MEK1 E102-I103
• The permitted mutations shown above are for MEK1. MEK1 and MEK2 are closely related, are structurally similar, share 79% amino acid identity, and they share equal ability to phosphylate their ERK substrates30. While the experiments performed above classify individual MEK1 mutations only, the class 3 mutations in MEK1 all share in-frame deletions that remove a potent negative regulatory element of MEK1. These are easily distinguishable from other mutations in MEK1. Therefore, the identification of exclusionary class 3 MEK2 alterations will be straightforward as well, with paralogous mutant residues in MEK1 and MEK2 defined in the manuscript above. A table showing the permitted enrolling paralogous class 1 and class 2 residues are shown in the table below, again with the caveat that rare mutations in MEK2 not listed in the table below may be eligible at the discretion of the principal investigator.
• MEK1: F53, Q56, K57, V60, D67, C121, P124, Y130, E203 MEK2: F57, Q60, K61, V64, D71, C125, P128, Y134, E207
• All Arms:
• Patient (or Legally Authorized Representative [LAR]) must sign written informed consent form before any study-specific procedure is performed
• ECOG performance score of 0 or 1
• Life expectancy of ≥3 months
• At least one tumor lesion measurable by RECIST 1.1. A lesion in a previously irradiated area may be considered as measurable disease if there is objective evidence of progression of the lesion by RECIST 1.1 (Eisenhauer EA et al, 2009) between the prior radiotherapy and the screening CT or MRI scan.
• Adequate bone marrow function at screening, as determined by:
• Absolute neutrophil count (ANC) >1,500/mm3 (CTCAE Grade ≤1)
• Platelet count >100,000 mm³
• Hemoglobin >9.0 mg/dL

You may not qualify if…

• Subjects are excluded from the study if any of the following criteria apply:
• Medical and surgical history
• History of HIV with the following exceptions:
• ° Patients with CD4+ T-cell (CD4+) counts ≥ 350 cells/uL
• History of AIDS-defining opportunistic infection with the following exceptions:
• Patients without opportunistic infection within the past 12 months
• Patients on prophylactic antimicrobials unless the specific antimicrobial drug(s) has an interaction or overlapping toxicity with the proposed treatment as determined by the investigator
• History of active Hepatitis B or Hepatitis C infection at screening with the following exceptions:
• Patients with Hepatitis B on a suppressive antiviral therapy
• Patients with Hepatitis C who have completed curative antiviral treatment and have an undetectable viral load
• History (within 5 years) or current evidence of neoplastic disease other than the cancer under study, except cervical carcinoma in situ, superficial noninvasive bladder tumors, curatively treated Stage I-II non-melanoma skin cancer, or any other previous cancer curatively treated <5 years before the start of treatment.
• Current evidence of untreated/unstable symptomatic primary CNS tumor, metastases, leptomeningeal carcinomatosis, or spinal cord compression. Exception: Patients are eligible if neurological symptoms are stable for 14 days prior to the first treatment dose and no CNS surgery or radiation has been performed for 28 days, or 14 days of SRS.
• Current evidence of CTCAE Grade >1 toxicity before the start of treatment, except for hair loss.
• ° Subjects with Grade 2 neuropathy may be eligible at the investigator's discretion.
• History or current evidence of ocular abnormalities on ophthalmologic examination that would be considered a risk factor for central serous retinopathy, RVO or neovascular macular degeneration (mild and controlled age-related macular degeneration may be acceptable at the investigator's discretion)
• Current evidence of incomplete recovery from surgery or radiotherapy at screening or planned major surgery or radiotherapy during the treatment. Minor elective surgery may be acceptable at the investigator's discretion.
• History or current evidence of significant (CTCAE Grade ≥2) infection or wound within 2 weeks before the start of treatment.
• History or current evidence of significant cardiovascular disease within 6 months before the start of treatment. This includes, but may not be limited to: unstable angina, new-onset angina, myocardial infarction, arterial thrombosis, pulmonary embolism, CVI/TIA/stroke, pericarditis (any CTCAE grade), pericardial effusion (CTCAE Grade ≥2), non-malignant pleural effusion (CTCAE Grade ≥2), malignant pleural effusion (CTCAE Grade ≥3), congestive heart failure (NYHA Class II - IV) or cardiac arrhythmia requiring anti-arrhythmic therapy, except the following
• Subjects receiving digoxin, calcium channel blockers, or beta-adrenergic blockers may be eligible at the investigator's discretion if the dose has been stable for ≥2 weeks before the start of treatment.
• Subjects with sinus arrhythmia and infrequent premature ventricular contractions may be eligible at the investigator's discretion.
• History or current evidence of malabsorption syndrome, major surgical GI resection or other GI conditions that may impair absorption of mirdametinib
• Known or suspected hypersensitivity or allergy to any of the study drugs or excipients contained in the study drug formulations. In addition, allergy to other medications or other type of hypersensitivity may warrant exclusion at the investigator's discretion.
• Female subjects who are pregnant or breastfeeding.
• History or current evidence of any other medical or psychiatric condition or addictive disorder, or laboratory abnormality that, in the opinion of the investigator, may increase the risks associated with study participation, or require treatments that may interfere with the conduct of the study or the interpretation of study results.
• Prior or concomitant treatments

Where it is running

• Memorial Sloan Kettering Monmouth (Limited protocol activities) — Middletown, New Jersey, United States
• Memorial Sloan Kettering Cancer Center @ Suffolk-Commack (Limited protocol activity) — Commack, New York, United States
• Memorial Sloan Kettering Westchester (Limited Protocol Activities) — Harrison, New York, United States
• Memorial Sloan Kettering Cancer Center (All Protocol Activities) — New York, New York, United States

Full record on ClinicalTrials.gov

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