Testing Binimetinib as a Potential Targeted Treatment in Cancers With NRAS Genetic Changes (MATCH-Subprotocol Z1A)

NCT04439344 | Active Not Recruiting Phase 2 Results DMC

• 4 other identifiers: NCI-2020-03374EAY131-Z1AU10CA180820U24CA196172
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II MATCH treatment trial investigates the good and bad effects of binimetinib in patients whose cancer has a genetic change called NRAS mutation. Binimetinib blocks proteins called MEK1 and MEK2, which may be needed for cancer cell growth when an NRAS mutation is present. Researchers hope to learn if binimetinib will shrink this type of cancer or stop its growth.

Conditions

Advanced Lymphoma; Refractory Lymphoma; Advanced Malignant Solid Neoplasm; Hematopoietic and Lymphoid Cell Neoplasm; Refractory Malignant Solid Neoplasm; Refractory Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  ORR is defined as the percentage of patients whose tumors have a complete or partial response to treatment among eligible and treated patients. Objective response rate is defined consistent with Response Evaluation Criteria in Solid Tumors version 1.1 criteria for solid tumors, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. For each treatment arm, 90% two-sided binomial exact confidence interval will be calculated for ORR.

  Tumor assessments occurred at baseline, then every 2 cycles for the first 26 cycles and every 3 cycles thereafter until disease progression, up to 3 years post registration

Secondary Outcomes (2)

• 6-Month Progression-free Survival (PFS) Rate

  Tumor assessments occurred at baseline, then every 2 cycles for the first 26 cycles, and every 3 cycles thereafter until disease progression, up to 3 years post registration, from which 6-month PFS is determined

• Progression Free Survival (PFS)

  Assessed at baseline, then every 2 cycles for the first 26 cycles and every 3 cycles thereafter until disease progression, up to 3 years post registration

Study Arms (1)

Treatment (binimetinib)

EXPERIMENTAL

Patients receive binimetinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Binimetinib

Interventions

Binimetinib DRUG

Given PO

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

Treatment (binimetinib)

Eligibility Criteria

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

You may qualify if:

• Patients must have met applicable eligibility criteria in the Master MATCH Protocol prior to registration to treatment subprotocol
• Patients must have NRAS mutation in codon 12, 13, 61 as determined via the MATCH Master Protocol
• Patients must have an electrocardiogram (ECG) within 8 weeks prior to treatment assignment and must have no clinically significant abnormalities in rhythm, conduction or morphology of resting ECG (e.g. complete left bundle branch block, third degree heart block)
• Creatinine =\< 1.5 mg/dL, or calculated creatinine clearance (determined as per Cockcroft-Gault) \>= 50mL/min
• Patients must have adequate cardiac function:
• Left ventricular ejection fraction (LVEF) \>= 50% as determined by a multigated acquisition (MUGA) scan or echocardiogram,
• QTc interval =\< 480 ms

You may not qualify if:

• Patients must not have known hypersensitivity to binimetinib or compounds of similar chemical or biologic composition
• Patients with melanoma are excluded
• Patients must not have any active central nervous system (CNS) lesion (i.e., those with radiographically unstable, symptomatic lesions) and/or leptomeningeal metastases
• NOTE: Patients treated with stereotactic radiotherapy or surgery are eligible if the patient remained without evidence of CNS disease progression \>= 3 months. Patients must be off corticosteroid therapy for \>= 3 weeks
• Patients must not have a history or current evidence of retinal vein occlusion (RVO) or predisposing factors to RVO (e.g. uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes)
• Patients must not have a history of retinal degenerative disease
• Patients must not have a history of Gilbert's syndrome
• Patients must not have uncontrolled arterial hypertension despite medical treatment
• Patients must not have active hepatitis B, and/or active hepatitis C infection
• Patients must not have neuromuscular disorders that are associated with elevated creatine kinase (CK) (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy)
• Patients must not have impairment of gastrointestinal function or gastrointestinal disease (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection)
• Patients who have received prior MEK inhibitors are excluded

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

ECOG-ACRIN Cancer Research Group

Philadelphia, Pennsylvania, 19103, United States

Location

MeSH Terms

Conditions

Hematologic Neoplasms; Lymphoma; Multiple Myeloma

Interventions

binimetinib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders

Results Point of Contact

• Title: Study Statistician
• Organization: ECOG-ACRIN Statistical Office

eatrials@jimmy.harvard.edu

617-632-3012

Study Officials

• James M Cleary

  ECOG-ACRIN Cancer Research Group

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 18, 2020
• First Posted: June 19, 2020
• Study Start: May 31, 2016
• Primary Completion: May 3, 2019
• Study Completion (Estimated): March 31, 2027
• Last Updated: May 7, 2026
• Results First Posted: August 17, 2021

Record last verified: 2026-05

Locations

US (1)