Mirdametinib + Palbociclib for Liposarcoma

Recruiting at 6 trial locations

Overseen By Olayode Babatunde, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: CYP3A inducers, UGT inhibitors

Disqualifiers: Uncontrolled infection, Heart failure, Glaucoma, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

54 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two drugs, mirdametinib and palbociclib, to determine their safety and effectiveness in treating liposarcoma that cannot be surgically removed or has metastasized. Researchers will explore different doses of mirdametinib (a MEK inhibitor) alongside a fixed dose of palbociclib (a CDK4/6 inhibitor) to identify the safest and most effective dose for future studies. Individuals with liposarcoma that has recurred, spread, or cannot be surgically removed, and who have experienced disease progression, may be suitable candidates. As a Phase 1, Phase 2 trial, this study aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking research.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot take medications that strongly affect certain liver enzymes (CYP3A or UGT). If you're on such medications, you might need to stop or adjust them before joining the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that palbociclib, one of the drugs in this trial, may help treat liposarcoma, a type of cancer. Previous studies found that palbociclib can sometimes shrink tumors, although results vary from person to person.

Regarding safety, palbociclib has been used for other conditions and is generally well-tolerated. However, some side effects have been reported, such as low blood cell counts, tiredness, and nausea.

Researchers are testing mirdametinib with palbociclib to see if they work well together. Since this combination is still under study, information on its safety is limited. The goal is to find the safest dose when using both drugs together.

This trial is in the early stages, focusing mainly on safety and finding the right dose. Researchers are still evaluating how safe the combination is. Participants will help researchers learn how well the treatment is tolerated and what side effects might occur. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for liposarcoma, which often rely on traditional chemotherapy and radiation, mirdametinib and palbociclib work differently by targeting specific pathways involved in cancer cell growth. Mirdametinib inhibits the MEK pathway, a key player in cell division and survival, while palbociclib targets CDK4/6, proteins that regulate the cell cycle. This combination aims to more precisely attack the cancer cells, potentially leading to improved outcomes and fewer side effects compared to conventional therapies. Researchers are excited because these targeted treatments could offer new hope for patients with advanced liposarcoma, where options are currently limited.

What evidence suggests that mirdametinib and palbociclib might be an effective treatment for liposarcoma?

This trial will evaluate the combination of mirdametinib and palbociclib for treating liposarcoma, a type of cancer. Studies have shown that these drugs might help by targeting specific proteins that promote cancer cell growth. Research indicates that palbociclib can slow cancer growth in some patients by blocking proteins called CDK4/6. Mirdametinib may enhance this effect by blocking another pathway that aids cell growth. Early findings suggest that using these treatments together could be more effective by attacking the cancer in different ways. However, further research is needed to confirm these results. ^{1 2 3 4 6}

Who Is on the Research Team?

Olayode Babatunde, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for individuals with liposarcoma, a type of soft tissue tumor that's metastatic, recurrent, or can't be removed by surgery. Participants should not have had prior treatments with similar drugs to those being tested and must be able to take oral medication.

Inclusion Criteria

I can swallow pills.

I have had any number of previous treatments.

My organs and bone marrow are working well.

Exclusion Criteria

Patients receiving any other investigational agents

I've had severe side effects from previous cancer treatments targeting specific proteins.

I have severe heart failure diagnosed within the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Dose escalation phase to determine the maximum tolerated dose of mirdametinib in combination with palbociclib

Up to 1 year

Phase II Treatment

Participants receive the recommended phase 2 dose (RP2D) of mirdametinib plus palbociclib

18 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Mirdametinib
• Palbociclib

Trial Overview

The study is testing the effectiveness and safety of combining two drugs: Mirdametinib and Palbociclib. Different doses of Mirdametinib will be used alongside a fixed dose of Palbociclib to determine the best safe dosage for future studies.

How Is the Trial Designed?

Group I: Phase II Experimental Treatment 2 Interventions

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.

Group II: Phase I Experimental Treatment 2 Interventions

Dose escalation phase

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

SpringWorks Therapeutics, Inc.

Industry Sponsor

Trials

14

Recruited

900+

Published Research Related to This Trial

A genomic analysis of 56 liposarcoma samples revealed that while there were few gene mutations, over half of the samples exhibited gene amplifications, particularly of MDM2, CDK4, and receptor tyrosine kinases (RTKs).

In laboratory tests, combining CDK4 and IGF1R inhibitors effectively suppressed the growth of a well-differentiated liposarcoma cell line with IGF1R amplification, suggesting that this combination therapy could be a promising treatment for patients with these tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Frequent amplification of receptor tyrosine kinase genes in welldifferentiated/ dedifferentiated liposarcoma. Asano, N., Yoshida, A., Mitani, S., et al.[2018]

In a study of 61 patients with well-differentiated and dedifferentiated liposarcoma treated with palbociclib, the median progression-free survival was only 9.2 months for WDLPS and 2.6 months for DDLPS, indicating limited efficacy of the treatment.

Surgical outcomes showed that while some patients underwent successful resections after palbociclib treatment, there was no overall survival benefit, and the treatment did not significantly prolong tumor control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world use of palbociclib monotherapy in retroperitoneal liposarcomas at a large volume sarcoma center. Nassif, EF., Cope, B., Traweek, R., et al.[2023]

In a phase 2 clinical trial involving 60 patients with advanced well-differentiated or dedifferentiated liposarcomas (WD/DDLS), palbociclib at a new dose of 125 mg daily for 21 days every 28 days resulted in a progression-free survival (PFS) rate of 57.2% at 12 weeks, indicating its efficacy in this patient population.

The treatment was associated with manageable hematologic toxic effects, primarily neutropenia, suggesting that this dosing schedule may be safer compared to the previously tested regimen of 200 mg for 14 days.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Progression-Free Survival Among Patients With Well-Differentiated or Dedifferentiated Liposarcoma Treated With CDK4 Inhibitor Palbociclib: A Phase 2 Clinical Trial. Dickson, MA., Schwartz, GK., Keohan, ML., et al.[2022]

The study of RG7112, an MDM2 antagonist, in 20 patients with MDM2-amplified liposarcoma showed significant activation of the P53 pathway, with P53 and P21 levels increasing by 4.86 and 3.48 times, respectively, after 8 days of treatment.

While RG7112 demonstrated the ability to inhibit tumor cell proliferation, resulting in one partial response and 14 cases of stable disease, it also caused adverse effects in all patients, with common issues including nausea and thrombocytopenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of the MDM2 antagonist RG7112 on the P53 pathway in patients with MDM2-amplified, well-differentiated or dedifferentiated liposarcoma: an exploratory proof-of-mechanism study. Ray-Coquard, I., Blay, JY., Italiano, A., et al.[2022]

In a Phase II trial involving 29 patients with advanced well-differentiated/dedifferentiated liposarcoma, sitravatinib achieved a progression-free rate at 12 weeks of 41%, meeting the primary endpoint of the study.

While sitravatinib showed some disease control, it did not result in any confirmed responses, and the most common side effects included diarrhea, hypertension, and hoarseness, indicating a need for careful monitoring of adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Single-Arm Phase II Trial of Sitravatinib in Advanced Well-Differentiated/Dedifferentiated Liposarcoma. Ingham, M., Lee, S., Van Tine, BA., et al.[2023]

Erdafitinib, a pan-FGFR inhibitor, shows promise in treating dedifferentiated liposarcoma (DDLPS) by reducing cell viability and inducing apoptosis, particularly in tumors with high FGFR1 and/or FGFR4 expression, which correlates with poor prognosis.

Combining erdafitinib with the MDM2 antagonist RG7388 enhances its effectiveness, leading to improved tumor suppression in vitro and in vivo, and has shown disease stabilization in a patient with refractory DDLPS for 12 weeks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel Therapeutic Insights in Dedifferentiated Liposarcoma: A Role for FGFR and MDM2 Dual Targeting. Dadone-Montaudié, B., Laroche-Clary, A., Mongis, A., et al.[2020]

Citations

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NCT06843967 | A Study of Mirdametinib in Combination ...

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, ...

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Mirdametinib in Combination with Palbociclib for the ...

This phase I/II trial studies the safety, side effects, and best dose of mirdametinib when given together with palbociclib and to see how well it works.

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reporter.nih.gov

reporter.nih.gov/project-details/11228162

RePORT RePORTER - National Institutes of Health (NIH) |

PROJECT SUMMARY/ABSTRACT CDK4/6 inhibitors (CDK4/6i) have shown promise for the treatment of dedifferentiated liposarcoma (DDLS). Palbociclib received ...

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A Study of Mirdametinib in Combination With Palbociclib ...

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, ...

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tandfonline.com/doi/full/10.1080/1120009X.2025.2557678?src=

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Conclusion. Palbociclib showed modest activity with disease stabilization in some patients, highlighting the need for biomarker-driven and combination ...

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clinicaltrials.gov/study/NCT06843967?intr=MIRDAMETINIB&aggFilters=studyType:int&viewType=Table&rank=6

A Study of Mirdametinib in Combination With Palbociclib ...

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, ...