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

NCT05054374 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: 21-288
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Breast Cancer; Breast Cancer Stage IV; HER2-negative Breast Cancer; Solid Carcinoma; MEK1 Gene Mutation; MEK2 Gene Mutation; Metastatic Breast Cancer

Keywords

Advanced solid cancers; Metastatic Breast Cancer; Breast cancer; Breast cancer stage IV; HER2-negative Breast Cancer; MEK1 Gene Mutation; MEK2 Gene Mutation; Solid Carcinoma; 21-288; mirdametinib; fulvestrant; postmenopausal; estrogen receptor positive metastatic breast cancer; estrogen receptor positive; Memorial Sloan Kettering Cancer Center

Outcome Measures

Primary Outcomes (1)

• Dose Limiting Treatment/DLT Evaluable Population

  DLT Evaluable Population consists of patients who receive at least 80% of planned total doses of mirdametinib in cycle 1 (in Arm 1 only, also both doses of fulvestrant) and are observed within 28 days following the first dose of mirdametinib or patients who experience a DLT.

  28 days from first day of treatment

Study Arms (4)

Arm 1, Part 1 - mirdametinib in combination with fulvestrant

EXPERIMENTAL

Postmenopausal patients with estrogen receptor positive metastatic breast cancer harboring NF1 loss of function or another alteration of the MAPK pathway. Part 1: safety run-in (confirmation of the RP2D for mirdametinib in combination with the standard recommended dose of fulvestrant). This part may include the mirdametinib dose de-escalation according to the 3+3 design if necessary

Drug: Mirdametinib; Drug: Fulvestrant

Arm 1, Part 2 - mirdametinib in combination with fulvestrant

EXPERIMENTAL

Postmenopausal patients with estrogen receptor positive metastatic breast cancer harboring NF1 loss of function or another alteration of the MAPK pathway. Part 2: dose expansion cohorts where the mirdametinib RP2D will be administered in combination with the standard recommended dose of fulvestrant

Drug: Mirdametinib; Drug: Fulvestrant

Arm 2, Part 1 - mirdametinib as single agent

EXPERIMENTAL

Adult patients with advanced solid cancers driven by the alteration of the MAPK pathway Part 1: mirdametinib dose escalation to MTD or RP2D according to the 3+3 design

Drug: Mirdametinib

Arm 2, Part 2 - mirdametinib as single agent

EXPERIMENTAL

Adult patients with advanced solid cancers driven by the alteration of the MAPK pathway Part 2: dose expansion cohorts

Drug: Mirdametinib

Interventions

Mirdametinib DRUG

Dose Level -2INT: 2mg PO BID, 3 weeks on/1 week off Dose Level -2: 2mg PO BID given continuously Dose Level -1INT: 3mg PO BID, 3 weeks on/1 week off Dose Level -1: 3mg PO BID given continuously Dose Level 1: 4mg PO BID given continuously Dose Level 2: 6mg PO BID given continuously Dose Level 3: 8mg PO BID given continuously

Arm 1, Part 1 - mirdametinib in combination with fulvestrant; Arm 1, Part 2 - mirdametinib in combination with fulvestrant; Arm 2, Part 1 - mirdametinib as single agent; Arm 2, Part 2 - mirdametinib as single agent

Fulvestrant DRUG

The starting dose of mirdametinib in combination with fulvestrant in each Dose Level will be as follows: * Dose Level 1: mirdametinib 4 mg BID PO + fulvestrant * (Only to be triggered pending DLTs on higher Dose Levels as described below) * Dose Level -2: mirdametinib 2 mg BID PO continuous + fulvestrant, and Dose Level -2INT: mirdametinib 2 mg BID PO on 3 weeks on, 1 week off + fulvestrant

Arm 1, Part 1 - mirdametinib in combination with fulvestrant; Arm 1, Part 2 - mirdametinib in combination with fulvestrant

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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
• MEK1: F53, Q56, K57, V60, D67, C121, P124, Y130, E203 MEK2: F57, Q60, K61, V64, D71, C125, P128, Y134, E207

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)

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead

Study Sites (4)

Memorial Sloan Kettering Monmouth (Limited protocol activities)

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Cancer Center @ Suffolk-Commack (Limited protocol activity)

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester (Limited Protocol Activities)

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center (All Protocol Activities)

New York, New York, 10065, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Breast Neoplasms

Interventions

mirdametinib; Fulvestrant

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Results Point of Contact

• Title: Dr. Ezra Rosen, MD, PhD
• Organization: Memorial Sloan Kettering Cancer Center

rosene1@mskcc.org

646-888-6955

Study Officials

• Ezra Rosen, MD, PhD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 15, 2021
• First Posted: September 23, 2021
• Study Start: September 14, 2021
• Primary Completion: October 26, 2023
• Study Completion: October 26, 2023
• Last Updated: May 23, 2025
• Results First Posted: July 9, 2024

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share

Locations

US (4)