NCT05554354|TerminatedPhase 2ResultsFDA Drug

Study Stopped

Other - slow accrual

Testing the Use of Fulvestrant and Binimetinib Targeted Treatment for NF1 Mutation in Hormone Receptor-Positive Metastatic Breast Cancer (A ComboMATCH Treatment Trial)

Phase 2 Trial of Fulvestrant and Binimetinib in Patients With Hormone Receptor-Positive Metastatic Breast Cancer With Inactivating or Inferred Inactivating NF1 Alterations: A ComboMATCH Treatment Trial

National Cancer Institute (NCI)ClinicalTrials.gov

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3 other identifiers

NCI-2022-07265EAY191-N2U10CA180868

Study Type

interventional

Target

Locations

2 countries

Sites

196

Timeline

RegisteredSep 2022

StartedSep 2024

CompletionApr 2025

Brief Summary

This phase II ComboMATCH treatment trial compares the usual treatment alone (fulvestrant) to using binimetinib plus the usual treatment in patients with hormone receptor positive breast cancer that has spread from where it first started to other places in the body (metastatic) and has an NF1 genetic change. Fulvestrant is a hormonal therapy that binds to estrogen receptors in tumor cells, resulting in estrogen receptor destruction and decreased estrogen binding, which may inhibit the growth of estrogen-sensitive tumor cells. Binimetinib is a targeted therapy that may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. The addition of binimetinib to fulvestrant in breast cancers with an NF1 genetic change could increase the percentage of tumors that shrink as well as lengthen the time that the tumors remain stable (without progression) as compared to fulvestrant alone.

Trial Health

Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

participants targeted

Target at below P25 for phase_2

Timeline

Completed

Started Sep 2024

Shorter than P25 for phase_2

Geographic Reach

2 countries

196 active sites

Status

terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

7 months study duration

First Submitted

Initial submission to the registry

September 22, 2022

Completed

4 days until next milestone

First Posted

Study publicly available on registry

September 26, 2022

Completed

2 years until next milestone

Study Start

First participant enrolled

September 13, 2024

Completed

7 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 4, 2025

Completed

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

April 4, 2025

Completed

11 months until next milestone

Results Posted

Study results publicly available

March 3, 2026

Completed

Last Updated

March 3, 2026

Status Verified

August 1, 2025

Enrollment Period

7 months

First QC Date

September 22, 2022

Results QC Date

February 17, 2026

Last Update Submit

February 17, 2026

Conditions

Metastatic HER2-Negative Breast Carcinoma Metastatic Hormone Receptor-Positive Breast Carcinoma Anatomic Stage IV Breast Cancer AJCC v8

Outcome Measures

Primary Outcomes (2)

Progression Free Survival (PFS) (Cohort I)
PFS of the two study arms will be compared by log-rank test (1-sided, alpha=0.1). Kaplan-Meier plot will be provided. Hazard ratio (HR) and the corresponding 95% confidence interval (CI) will be estimated by Cox proportional model using treatment as covariate.
The duration between randomization and progression or death from all cause, whichever happens first, assessed up to 5 years
Objective Response Rate (ORR) (Cohort II)
ORR is the percentage of patients who reaches a complete or partial response (defined by Response Evaluation Criteria in Solid Tumors \[RECIST\] version\[v\]1.1) within 4 months of the start of the treatment. ORR will be calculated as the proportion of patients achieved partial response (PR) or complete response (CR) within 4 months after the initiation of the treatment. ORR will be reported with corresponding 95% exact CI. Patients who have withdrawn from the study before any efficacy follow up are considered non-evaluable for clinical response and will be replaced.
Within 4 months of the start of treatment

Secondary Outcomes (6)

ORR for Each Study Arm (Cohort I)
Any time after the start of the treatment, assessed up to 5 years
ORR (Cohort II)
Any time after the start of the treatment, assessed up to 5 years
Clinical Benefit Rate
Any time after the start of the treatment, assessed up to 5 years
PFS (Cohort II)
The duration between randomization and progression or death from all cause, whichever happens first, assessed up to 5 years
Overall Survival (OS)
The duration between randomization and death of all causes, assessed up to 5 years
+1 more secondary outcomes

Other Outcomes (1)

Analysis of Integrated and Exploratory Biomarkers
Up to 5 years

Study Arms (3)

Cohort I (Arm I) (fulvestrant, binimetinib)

EXPERIMENTAL

Patients receive fulvestrant IM on day 1 and day 15 of cycle 1 and day 1 of subsequent cycles and binimetinib PO BID on days 15 to 28 of cycle 1 and day 1 through 28 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo a CT, MRI, or bone scan, ECHO or MUGA, and tumor biopsy, as well as possible blood sample collection during screening and on study.

Drug: BinimetinibProcedure: Biopsy ProcedureProcedure: Biospecimen CollectionProcedure: Bone ScanProcedure: Computed TomographyProcedure: Echocardiography TestDrug: FulvestrantProcedure: Magnetic Resonance ImagingProcedure: Multigated Acquisition Scan

Cohort I (Arm II)

ACTIVE COMPARATOR

Patients receive fulvestrant IM on day 1 and day 15 of cycle 1 and day 1 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who progress on fulvestrant alone may migrate to cohort II if they meet the migration eligibility criteria. Patients not willing to migrate to cohort II will have further therapy at the investigator's discretion. Patients undergo a CT, MRI, or bone scan and tumor biopsy, as well as ECHO or MUGA and possible blood sample collection during screening and on study.

Procedure: Biopsy ProcedureProcedure: Biospecimen CollectionProcedure: Bone ScanProcedure: Computed TomographyProcedure: Echocardiography TestDrug: FulvestrantProcedure: Magnetic Resonance ImagingProcedure: Multigated Acquisition Scan

Cohort II (fulvestrant, binimetinib)

EXPERIMENTAL

Patients receive fulvestrant IM on day 1 of each cycle and binimetinib PO BID on days 15-28 of cycle 1 and day 1 through 28 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo a CT, MRI, or bone scan, ECHO or MUGA and tumor biopsy, as well as possible blood sample collection during screening and on study.

Interventions

BinimetinibDRUG

Given PO

Also known as: ARRY 162, ARRY 438162, ARRY-162, ARRY-438162, ARRY162, ARRY438162, MEK 162, MEK-162, MEK162, Mektovi

Cohort I (Arm I) (fulvestrant, binimetinib)Cohort II (fulvestrant, binimetinib)

Biopsy ProcedurePROCEDURE

Undergo tumor biopsy

Also known as: Biopsy, BIOPSY_TYPE, Bx