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Also known as Mirdametinib (MEK Inhibitor)
Mirdametinib · 6 trials · 20 indications
To determine the best overall neurologic response rate
To determine the recommended phase 2 dose (RP2D) of mirdametinib plus palbociclib in patients with DDLPS
Phase II: To determine the progression-free survival rate at 18 weeks by RECIST 1.1
Phase 1 will test the safety and tolerability of multiple dose regimens of mirdametinib, in order to identify the recommended phase 2 dose(s) for phase 2a. The study will continue until one of the stopping conditions is met. * The RP2D(s) have been identified with sufficient accuracy (The dose regimen(s) selected as the RP2D have been fully enrolled with at least 3 cycles of treatment completed for all participants) * All dose regimens are deemed to have unacceptable safety The study will continue until one of the following stopping conditions is met. * The RP2D(s) have been identified with sufficient accuracy (The dose regimen(s) selected as the RP2D have been fully enrolled with at least 3 cycles of treatment completed for all participants) * All dose regimens are deemed to have unacceptable safety
Phase 2a of the study will test the efficacy and safety of a maximum of two RP2Ds in adults with NF1 and cNF.
Evaluate the efficacy of mirdametinib monotherapy at the RP2D in adults with NF1 and cNF. We will determine efficacy of Anti-tumor activity with 3D photography (Sum of the surface area, sum of the tumor volume, sum of the longest diameter) and Digital Caliper (Sum of the longest diameter).
The maximum tolerated dose (MTD) is empirically defined as the highest dose level at which six patients have been treated with at most one patient experiencing a dose-limiting toxicity (DLT) and the next higher dose level determined to be too toxic. The MTD estimate will not be available if the lowest dose level studied is too toxic or the highest dose level studied is considered safe. In the latter case, the highest studied safe dose may be considered as the recommended phase 2 dose (RP2D). The MTD estimation will be limited to evaluable patients and toxicity assessments from course 1 (28 days). We will require that at least 12 DLT evaluable subjects are assessed before the MTD/RP2D is declared.
Incidence of adverse event data at least possibly related to treatment will be summarized in cohort specific tables by grade and attribution throughout treatment.
Mirdametinib plasma concentration will be provided and area under the curve (AUC0-8h) estimated based on course 1, days 1 and 15 PK samples
The response rate, defined as the rate of minor response, partial response (PR), major response, or complete response (CR) will be calculated as the percentage of confirmed responders among all response assessable patients. These rates as well as their exact confidence intervals will be provided and will be summarized by each response category (i.e., PR, major response, and CR). Subjects without an assessment will be considered non-responders.
The response rate, defined as the rate of minor response, partial response (PR), major response, or complete response (CR) will be calculated as the percentage of confirmed responders among all response assessable patients. These rates as well as their exact confidence intervals will be provided and will be summarized by each response category (i.e., PR, major response, and CR). Subjects without an assessment will be considered non-responders.
Rate of stable disease from start of treatment until the time of progression or time of last follow-up.
Rate of stable disease from start of treatment until the time of progression or time of last follow-up.
Incidence of adverse event data at least possibly related to treatment will be summarized in cohort specific tables by grade and attribution throughout treatment.
| Arm | Type | Description |
|---|---|---|
| Cohort A: Mirdametinib | EXPERIMENTAL | 11 participants with refractory neurohistiocytosis will be treated with mirdametinib in continuous treatment cycles |
| Cohort B: Perioperative mirdametinib | EXPERIMENTAL | 15 participants with recurrent NF1-mutant glioma will be randomized in a 2:1 ratio to receive either perioperative mirdametinib (for 5 days) or no drug before standard of care surgery. All 15 participants will be treated with mirdametinib twice daily after surgery, continuously until clinical or radiographic progression of disease |
| Cohort B: No perioperative mirdametinib | NO_INTERVENTION | 15 participants with recurrent NF1-mutant glioma will be randomized in a 2:1 ratio to receive either perioperative mirdametinib (for 5 days) or no drug before standard of care surgery. All 15 participants will be treated with mirdametinib twice daily after surgery, continuously until clinical or radiographic progression of disease |
| Period 1 Mirdametinib | ACTIVE_COMPARATOR | Mirdametinib 6-mg single dose given orally alone on Day 1 as three 2-mg capsules following a 10-hour fast. |
| Period 2 Mirdametinib and carbamazepine | EXPERIMENTAL | Mirdametinib 6-mg single dose given orally on Day 22 in Period 2 as three 2-mg capsules following a 10-hour fast in combination with carbamazepine tablets that are administered orally according to the following schedule: * Days 8 and 9: 100 mg BID with meals * Days 10 and 11: 200 mg BID with meals * Days 12 through 21: 300 mg BID with meals * Day 22: 300 mg AM fasted, with mirdametinib, and 300 mg PM with meal * Days 23 through 28: 300 mg BID with meals * Days 29 through 30: no doses (observation only) |
| Moderate Hepatic Impairment | OTHER | - |
| Healthy Match Participants | OTHER | - |
| Severe Hepatic Impairment | OTHER | - |
| Phase I | EXPERIMENTAL | Dose escalation phase |
| Phase II | EXPERIMENTAL | During the phase II portion, 30 patients with advanced DDLPS will be enrolled. All patients in the phase II study will receive the RP2D of mirdametinib plus palbociclib. |
| Phase 1 | EXPERIMENTAL | For the Phase 1 portion, treatment will be administered continuously (Dose regimens 1, 2, 4) or intermittently (Dose regimen 3; 3 weeks on/1 week off) in 28-day cycles). All participants will receive study drug until: 1. cessation of study treatment due to death, intolerance, or withdrawal of consent from the study; 2. completion of 24 cycles of treatment (unless the investigator's benefit-risk assessment supports continued treatment); 3. participants enroll in the phase 2a portion of the study; 4. disease progression; or 5. Investigator's decision. Treatment period ends with the administration of the last dose. The study ends 30 days after the last dose |
| Phase 2 | EXPERIMENTAL | For the Phase 2 portion, treatment will be administered based on recommended RP2D from Phase 1. All participants will receive study drug until: 1. cessation of study treatment due to death, intolerance, or withdrawal of consent from the study; 2. completion of 24 cycles of treatment (unless the investigator's benefit-risk assessment supports continued treatment; 3. disease progression; or 4. Investigator's decision. Treatment period ends with the administration of the last dose. The study ends 30 days after the last dose. |
| Phase I: Recurrent and/or progressive low-grade glioma without prior exposure to MEK inhibitors | EXPERIMENTAL | Participants will receive mirdametinib at one of the dose levels twice daily days 1-28. For the first cycle of treatment, participants will take mirdametinib tablets dissolved in water. After the first cycle of treatment, participants may receive the medicine the same way (dissolved in water) or may receive capsules. Treatment repeats every 28 days for up to 26 cycles of treatment (24 months) in the absence of disease progression or unacceptable toxicity. |
| Phase 2, Cohort 1: Newly diagnosed and/or previously untreated (except surgery) | EXPERIMENTAL | Participants will receive the RP2D of mirdametinib. Therapy will be administered in cycles of 28 days and may be continued for up to 24 months (26 cycles) in absence of disease progression or unacceptable toxicity. |
| Phase 2, Cohort 2: Recurrent and/or Progressive without prior exposure to MEK inhibitors | EXPERIMENTAL | Participants will receive the RP2D of mirdametinib. Participants may take mirdametinib tablets dissolved in water, or receive capsules. Therapy will be administered in cycles of 28 days and may be continued for up to 24 months (26 cycles) in absence of disease progression or unacceptable toxicity. |
| Phase 2, Cohort 3a: | EXPERIMENTAL | Participants with recurrent and/or progressive low-grade glioma who previously received ≥ 6 courses MEK inhibitor (including mirdametinib) and did not progress while on active MEKi therapy. Participants will receive the RP2D of mirdametinib. Participants with previous exposure to mirdametinib may receive a starting dose lower than the RP2D, depending on the dose they tolerated during their previous exposure. Participants may take mirdametinib tablets dissolved in water, or receive capsules. Therapy will be administered in cycles of 28 days and may be continued for up to 24 months (26 cycles) in absence of disease progression or unacceptable toxicity. |
| Phase 2, Cohort 3b: | EXPERIMENTAL | Participants with recurrent and/or progressive low-grade glioma who previously received ≥ 6 courses MEK inhibitor (including mirdametinib) and did not progress while on active MEKi therapy. Participants will receive the RP2D of mirdametinib. Participants may take mirdametinib tablets dissolved in water, or receive capsules. Therapy will be administered in cycles of 28 days and may be continued for up to 24 months (26 cycles) in absence of disease progression or unacceptable toxicity. |
| Name | Type | Description |
|---|---|---|
| Mirdametinib | DRUG | Mirdametinib is a highly selective and potent, non-ATP-competitive oral inhibitor of MEK1 and MEK2 kinases |
| Mirdametinib and Carbamazepine | DRUG | Drug: Mirdametinib 6-mg single dose given orally on Day 22. Drug: Carbamazepine Carbamazepine extended-release (ER) (Carbamazepine ER will be given orally twice daily for 21 days with a titration schedule \[100 mg BID for 2 days, 200 mg BID for 2 days, and then 300 mg BID\]). |
| Mirdametinib (MEK Inhibitor) | DRUG | Mirdametinib will be administered as a single, oral, 4 mg dose in the morning on Day 1 for each study participant enrolled in the study. |
| Palbociclib | DRUG | Palbociclib (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. |
Inclusion criteria - Cohorts A and B Demographic Characteristics a. Be \> 18 years of age General Criteria 1. Have Karnofsky Performance Status (KPS) of ≥ 70% or ECOG Performance Status of ≤ 2 2. Is able to understand and provide written informed consent for the trial prior to any study-specific...
Mirdametinib is an investigational small molecule being studied for well differentiated liposarcoma, NF1, low-grade glioma, and central nervous system tumors. It is also being evaluated in healthy participants for pharmacokinetic studies. The drug is in Phase 1 clinical development and is not yet approved by the FDA.
Mirdametinib is a kinase inhibitor, belonging to the -tinib class of drugs. It targets MEK, a kinase involved in cell signaling pathways. By inhibiting MEK, it may block tumor cell growth and proliferation. This mechanism is being explored in oncology indications such as low-grade glioma and NF1.
Mirdametinib is being developed by SpringWorks Therapeutics, Inc., a biopharmaceutical company traded on NASDAQ under the ticker SWTX. The company is conducting clinical trials for this investigational drug across multiple oncology indications.
Mirdametinib is currently in Phase 1 clinical development. It is an investigational drug and has not received FDA approval. Clinical trials are ongoing to evaluate its safety, pharmacokinetics, and potential efficacy in various conditions.
Mirdametinib is being studied in several Phase 1 trials. NCT04923126 evaluates it in children and young adults with low-grade glioma. NCT06159166 tests it in adults with NF1 and cutaneous neurofibromas. NCT06997276 and NCT07279233 assess its pharmacokinetics in healthy participants with hepatic impairment or enzyme induction.
Yes, Mirdametinib is a MEK inhibitor, as indicated by its alternative name. It belongs to the kinase inhibitor class and is being investigated for its ability to block MEK signaling in tumors. This mechanism is relevant to its potential use in oncology.