Advanced LymphomaPhase 2NCT04439344
Testing Binimetinib as a Potential Targeted Treatment in Cancers With NRAS Genetic Changes (MATCH-Subprotocol Z1A)
A Phase 2 study testing Binimetinib in people with Advanced Lymphoma and Advanced Malignant Solid Neoplasm, run by National Cancer Institute (NCI) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Lymphoma, Advanced Malignant Solid Neoplasm, Hematopoietic and Lymphoid Cell Neoplasm
- What is being tested?
- Binimetinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 53 participants
- Where
- 1 siteUnited States
- Study dates
- 31 May 2016to 31 Mar 2027
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
ECOG-ACRIN Cancer Research Group
Philadelphia, Pennsylvania, 19103
About this study
Official title: MATCH Treatment Subprotocol Z1A: Binimetinib in Patients With Tumors (Other Than Melanoma) With NRAS Mutations
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.
Read the detailed description
PRIMARY OBJECTIVE:
- To evaluate the proportion of patients with objective response (OR) to targeted study agent(s) in patients with advanced refractory cancers/lymphomas/multiple myeloma.
SECONDARY OBJECTIVES:
- To evaluate the proportion of patients alive and progression free at 6 months of treatment with targeted study agent in patients with advanced refractory cancers/lymphomas/multiple myeloma.
II. To evaluate time until death or disease progression. III. To identify potential predictive biomarkers beyond the genomic alteration by which treatment is assigned or resistance mechanisms using additional genomic, ribonucleic acid (RNA), protein and imaging-based assessment platforms.
IV. To assess whether radiomic phenotypes obtained from pre-treatment imaging and changes from pre- through post-therapy imaging can predict objective response and progression free survival and to evaluate the association between pre-treatment radiomic phenotypes and targeted gene mutation patterns of tumor biopsy specimens.
OUTLINE:
Patients receive binimetinib orally (PO) twice daily (BID) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months if less than 2 years from study entry, and then every 6 months for year 3 from study entry.
- Conditions
- Advanced Lymphoma, Advanced Malignant Solid Neoplasm, Hematopoietic and Lymphoid Cell Neoplasm, Refractory Lymphoma, Refractory Malignant Solid Neoplasm, Refractory Multiple Myeloma
- Being tested
- Binimetinib
- Medical subject headings
- Hematologic Neoplasms, Lymphoma, Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BinimetinibDrug
Also called ARRY 162, ARRY 438162, ARRY-162, ARRY-438162
Given PO
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Binimetinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Progression free survival is defined as time from treatment start date to date of progression or death from any cause, whichever occurs first. Disease progression was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. 6 month PFS rate was estimated using the Kaplan-Meier method, which can provide a point estimate for any specific time point.
Measured: 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)
Progression free survival is defined as time from treatment start date to date of progression or death from any cause, whichever occurs first. Disease progression was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. Median PFS was estimated using the Kaplan-Meier method.
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jun 2020
- Study start31 May 2016
- Primary completion3 May 2019
- Study completion31 Mar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Advanced LymphomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 53 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- James M Cleary, Principal investigator, ECOG-ACRIN Cancer Research Group
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04439344
- Sponsor's protocol ID
- NCI-2020-03374
- Other IDs
- NCI-2020-03374, EAY131-Z1A, EAY131-Z1A, U10CA180820, U24CA196172
- Status last verified
- May 2026
- First submitted
- 18 Jun 2020
- Last updated
- 7 May 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 7 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- MATCH Treatment Subprotocol Z1A: Binimetinib in Patients With Tumors (Other Than Melanoma) With NRAS Mutations
- ClinicalTrials.gov ID
- NCT04439344
- Acronym / sponsor ID
- NCI-2020-03374
- Conditions
- Advanced Lymphoma, Advanced Malignant Solid Neoplasm, Hematopoietic and Lymphoid Cell Neoplasm, Refractory Lymphoma, Refractory Malignant Solid Neoplasm, Refractory Multiple Myeloma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 53 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 31 May 2016 (actual)
- Primary completion
- 3 May 2019 (actual)
- Study completion
- 31 Mar 2027 (estimated)
- First posted
- 19 Jun 2020 (actual)
- Results
- Posted 17 Aug 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
PRIMARY OBJECTIVE:
- To evaluate the proportion of patients with objective response (OR) to targeted study agent(s) in patients with advanced refractory cancers/lymphomas/multiple myeloma.
SECONDARY OBJECTIVES:
- To evaluate the proportion of patients alive and progression free at 6 months of treatment with targeted study agent in patients with advanced refractory cancers/lymphomas/multiple myeloma.
II. To evaluate time until death or disease progression. III. To identify potential predictive biomarkers beyond the genomic alteration by which treatment is assigned or resistance mechanisms using additional genomic, ribonucleic acid (RNA), protein and imaging-based assessment platforms.
IV. To assess whether radiomic phenotypes obtained from pre-treatment imaging and changes from pre- through post-therapy imaging can predict objective response and progression free survival and to evaluate the association between pre-treatment radiomic phenotypes and targeted gene mutation patterns of tumor biopsy specimens.
OUTLINE:
Patients receive binimetinib orally (PO) twice daily (BID) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months if less than 2 years from study entry, and then every 6 months for year 3 from study entry.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (binimetinib) | Experimental | Drug: BinimetinibPatients receive binimetinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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:
Key exclusion criteria (12 listed)
- 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
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BinimetinibAlso: ARRY 162, ARRY 438162, ARRY-162, ARRY-438162Given PO | Drug | Treatment (binimetinib) |
Primary outcome
Objective Response Rate (ORR)
Time frame: 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
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.
2 secondary outcomes
6-Month Progression-free Survival (PFS) Rate
Time frame: 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)
Time frame: 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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 May 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
James M Cleary principal investigator
ECOG-ACRIN Cancer Research Group
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Binimetinib in people with Advanced Lymphoma and Advanced Malignant Solid Neoplasm, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 7 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Aug 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (ORR) (time frame: 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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 May 2026.