Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Carcinoma

Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Fulvestrant

Estrogens

Antineoplastic Agents, Hormonal

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormones

Hormone Antagonists

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

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

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

Adult patients with advanced solid cancers driven by the alteration of the MAPK pathway

Part 2: dose expansion cohorts

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

Mirdametinib

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

Ezra Rosen, MD, PhD

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.

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

A Phase 1b / 2a, Open-label Platform Study to Evaluate Mirdametinib as Monotherapy or in Combination With Other Anticancer Agents in Patients With Advanced Solid Cancers Harboring MAPK-activating Mutations

Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

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.

Memorial Sloan Kettering Cancer Center

Symptoms and General Pathology

Nervous System Diseases

Diseases and Abnormalities at or Before Birth

Rare Diseases

Neoplasm Metastasis

Neurofibromatoses

Neurofibromatosis 1

Neurofibromatosis

Neurofibromatosis Type 1

Subjects will receive Abemaciclib 150 mg orally twice daily with LY3214996 200 mg orally daily until disease progression, unacceptable toxicity, or patient preference to withdraw from study.

Subjects will receive Abemaciclib 150 mg orally twice daily until disease progression, unacceptable toxicity, or patient preference to withdraw from study.

Abemaciclib

Subjects will recieve LY3214996 200 mg orally daily until disease progression, unacceptable toxicity, or patient preference to withdraw from study.

LY3214996

Anita Turk, MD

The purpose of CTO-IUSCC-0730 study is to assess the clinical efficacy of LY3214996 in combination with abemaciclib at the recommended phase 2 dose of LY3214996 200 mg orally daily and abemaciclib 150 mg orally twice daily. Patients will be treated until evidence of disease progression, non-compliance with study protocol, unacceptable major toxicity, at subject's own request for withdrawal, or if the study closes for any reason.

A Basket Trial of an ERK1/2 Inhibitor (LY3214996) in Combination With Abemaciclib.

A Phase 2 Basket Trial of an ERK1/2 Inhibitor (LY3214996) in Combination With Abemaciclib for Patients Whose Tumors Harbor Pathogenic Alterations in BRAF, RAF1, MEK1/2, ERK1/2, and NF1.

the number of patients who achieve a best overall response of complete response (CR) or partial response (PR) divided by the total number of patients treated (safety population)

CTCAE Version 5.0 will be used to summarize adverse events in the assessment of safety for incorporating LY3214996 in combination with abemaciclib. Summaries of treatment related adverse events in the population will be tabulated. All adverse events (AEs) will be presented in incidence tables coded by CTC term.

measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented

the time from the date of start of treatment to the first date of the observed clinical or radiologically documented PD or death due to any cause, whichever occurs first. For patients who are not known to have died or progressed as of the data-inclusion cut-off date, PFS time will be censored at the date of the last objective progression-free disease assessment prior to the date of any subsequent systematic anticancer therapy.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of Mirdametinib on Its Own or in Combination With Fulvestrant in People With Solid Tumor Cancer	NCT05054374	Breast Cancer Breast Cancer S... HER2-negative B... Solid Carcinoma MEK1 Gene Mutat... MEK2 Gene Mutat... Metastatic Brea...	Mirdametinib Fulvestrant	18 Years -	Memorial Sloan Kettering Cancer Center
A Basket Trial of an ERK1/2 Inhibitor (LY3214996) in Combination With Abemaciclib.	NCT04534283	Cancer Cancer Metastat... BRAF V600E MEK1 Gene Mutat... MEK2 Gene Mutat... ERK Mutation RAF1 Gene Mutat...	Abemaciclib LY3214996	18 Years -	Indiana University
A Basket Trial of an ERK1/2 Inhibitor (LY3214996) in Combination With Abemaciclib.	NCT04534283	Cancer Cancer Metastat... BRAF V600E MEK1 Gene Mutat... MEK2 Gene Mutat... ERK Mutation RAF1 Gene Mutat...	Abemaciclib LY3214996	18 Years -	Indiana University

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