Trial Outcomes & Findings for Testing Binimetinib as a Potential Targeted Treatment in Cancers With NRAS Genetic Changes (MATCH-Subprotocol Z1A) (NCT NCT04439344)

Last Updated: 2025-11-19

Results Overview

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.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE2

Target enrollment

53 participants

Primary outcome timeframe

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

Results posted on

2025-11-19

Participant Flow

Subprotocol Z1A was activated on May 31, 2016. A total of 114 patients were assigned to this arm after screening, all from screening cohort. Of the 114 patients, 53 patients were enrolled to arm Z1A in the period from May 31, 2016 and June 7, 2018.

To be assigned to a specific MATCH subprotocol, patients needed to submit a tumor biopsy for molecular characterization and those with molecular variants addressed by treatments included in the trial entered corresponding MATCH subprotocol. For the subprotocol Z1A, patients had to have a tumor harboring a codon 12, 13, or 61 NRAS-mutation.

Participant milestones

Participant milestones
Measure	Treatment (Binimetinib) Patients receive binimetinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Binimetinib: Given PO
Overall Study STARTED	53
Overall Study Started Protocol Therapy	50
Overall Study Eligible	47
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	53

Reasons for withdrawal

Reasons for withdrawal
Measure	Treatment (Binimetinib) Patients receive binimetinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Binimetinib: Given PO
Overall Study Never started threapy	3
Overall Study Ineligible	3
Overall Study Adverse Event	13
Overall Study Death	2
Overall Study Disease progression	29
Overall Study Withdrawal by Subject	2
Overall Study Alternative therapy	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment (Binimetinib) n=47 Participants Patients receive binimetinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Binimetinib: Given PO
Age, Continuous	60 years
Sex: Female, Male Female	29 Participants
Sex: Female, Male Male	18 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	40 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	2 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Black or African American	3 Participants
Race (NIH/OMB) White	40 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants

PRIMARY outcome

Timeframe: 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

Population: Patients who were eligible and received protocol treatment

Outcome measures

Outcome measures
Measure	Treatment (Binimetinib) n=47 Participants Patients receive binimetinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Binimetinib: Given PO
Objective Response Rate (ORR)	0.021 percentage of participants Interval 0.001 to 0.097

SECONDARY outcome

Timeframe: 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

Population: Patients who were eligible and received protocol treatment

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.

Outcome measures

Outcome measures
Measure	Treatment (Binimetinib) n=47 Participants Patients receive binimetinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Binimetinib: Given PO
6-Month Progression-free Survival (PFS) Rate	0.292 percentage of participants Interval 0.194 to 0.44

SECONDARY outcome

Timeframe: 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

Population: Patients who were eligible and received protocol treatment

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.

Outcome measures

Outcome measures
Measure	Treatment (Binimetinib) n=47 Participants Patients receive binimetinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Binimetinib: Given PO
Progression Free Survival (PFS)	3.5 months Interval 1.8 to 5.8

Adverse Events

Treatment (Binimetinib)

Serious events: 24 serious events

Other events: 44 other events

Deaths: 43 deaths

Serious adverse events

Serious adverse events
Measure	Treatment (Binimetinib) n=50 participants at risk Patients receive binimetinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Binimetinib: Given PO
Cardiac disorders Heart failure	2.0% 1/50 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All 53 patients enrolled to the trial were monitored for mortality, the 50 treated patients were monitored for adverse events.
Cardiac disorders Myocardial infarction	2.0% 1/50 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All 53 patients enrolled to the trial were monitored for mortality, the 50 treated patients were monitored for adverse events.
General disorders Edema limbs	2.0% 1/50 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All 53 patients enrolled to the trial were monitored for mortality, the 50 treated patients were monitored for adverse events.
General disorders Fatigue	2.0% 1/50 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All 53 patients enrolled to the trial were monitored for mortality, the 50 treated patients were monitored for adverse events.
General disorders Multi-organ failure	2.0% 1/50 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All 53 patients enrolled to the trial were monitored for mortality, the 50 treated patients were monitored for adverse events.
Skin and subcutaneous tissue disorders Rash acneiform	6.0% 3/50 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All 53 patients enrolled to the trial were monitored for mortality, the 50 treated patients were monitored for adverse events.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, specify	2.0% 1/50 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All 53 patients enrolled to the trial were monitored for mortality, the 50 treated patients were monitored for adverse events.
Gastrointestinal disorders Mucositis oral	2.0% 1/50 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All 53 patients enrolled to the trial were monitored for mortality, the 50 treated patients were monitored for adverse events.
Gastrointestinal disorders Nausea	2.0% 1/50 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All 53 patients enrolled to the trial were monitored for mortality, the 50 treated patients were monitored for adverse events.
Gastrointestinal disorders Small intestinal obstruction	2.0% 1/50 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All 53 patients enrolled to the trial were monitored for mortality, the 50 treated patients were monitored for adverse events.
Infections and infestations Urinary tract infection	2.0% 1/50 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All 53 patients enrolled to the trial were monitored for mortality, the 50 treated patients were monitored for adverse events.
Investigations Alanine aminotransferase increased	2.0% 1/50 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All 53 patients enrolled to the trial were monitored for mortality, the 50 treated patients were monitored for adverse events.
Investigations Alkaline phosphatase increased	2.0% 1/50 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All 53 patients enrolled to the trial were monitored for mortality, the 50 treated patients were monitored for adverse events.
Investigations Aspartate aminotransferase increased	2.0% 1/50 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All 53 patients enrolled to the trial were monitored for mortality, the 50 treated patients were monitored for adverse events.
Investigations CPK increased	4.0% 2/50 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All 53 patients enrolled to the trial were monitored for mortality, the 50 treated patients were monitored for adverse events.
Investigations Ejection fraction decreased	2.0% 1/50 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All 53 patients enrolled to the trial were monitored for mortality, the 50 treated patients were monitored for adverse events.
Investigations Lymphocyte count decreased	4.0% 2/50 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All 53 patients enrolled to the trial were monitored for mortality, the 50 treated patients were monitored for adverse events.
Investigations White blood cell decreased	2.0% 1/50 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All 53 patients enrolled to the trial were monitored for mortality, the 50 treated patients were monitored for adverse events.
Metabolism and nutrition disorders Anorexia	2.0% 1/50 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All 53 patients enrolled to the trial were monitored for mortality, the 50 treated patients were monitored for adverse events.
Metabolism and nutrition disorders Dehydration	2.0% 1/50 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All 53 patients enrolled to the trial were monitored for mortality, the 50 treated patients were monitored for adverse events.
Metabolism and nutrition disorders Hypoalbuminemia	2.0% 1/50 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All 53 patients enrolled to the trial were monitored for mortality, the 50 treated patients were monitored for adverse events.
Metabolism and nutrition disorders Hyponatremia	2.0% 1/50 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All 53 patients enrolled to the trial were monitored for mortality, the 50 treated patients were monitored for adverse events.
Metabolism and nutrition disorders Hypophosphatemia	2.0% 1/50 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All 53 patients enrolled to the trial were monitored for mortality, the 50 treated patients were monitored for adverse events.
Musculoskeletal and connective tissue disorders Muscle weakness lower limb	2.0% 1/50 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All 53 patients enrolled to the trial were monitored for mortality, the 50 treated patients were monitored for adverse events.
Musculoskeletal and connective tissue disorders Muscle weakness upper limb	2.0% 1/50 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All 53 patients enrolled to the trial were monitored for mortality, the 50 treated patients were monitored for adverse events.
Nervous system disorders Syncope	2.0% 1/50 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All 53 patients enrolled to the trial were monitored for mortality, the 50 treated patients were monitored for adverse events.
Eye disorders Eye disorders - Other, specify	2.0% 1/50 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All 53 patients enrolled to the trial were monitored for mortality, the 50 treated patients were monitored for adverse events.
Vascular disorders Hypertension	12.0% 6/50 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All 53 patients enrolled to the trial were monitored for mortality, the 50 treated patients were monitored for adverse events.

Other adverse events

Other adverse events
Measure	Treatment (Binimetinib) n=50 participants at risk Patients receive binimetinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Binimetinib: Given PO
Blood and lymphatic system disorders Anemia	14.0% 7/50 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All 53 patients enrolled to the trial were monitored for mortality, the 50 treated patients were monitored for adverse events.
General disorders Edema face	10.0% 5/50 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All 53 patients enrolled to the trial were monitored for mortality, the 50 treated patients were monitored for adverse events.
General disorders Edema limbs	34.0% 17/50 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All 53 patients enrolled to the trial were monitored for mortality, the 50 treated patients were monitored for adverse events.
General disorders Fatigue	36.0% 18/50 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All 53 patients enrolled to the trial were monitored for mortality, the 50 treated patients were monitored for adverse events.
General disorders General disorders and administration site conditions - Other	6.0% 3/50 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All 53 patients enrolled to the trial were monitored for mortality, the 50 treated patients were monitored for adverse events.
Skin and subcutaneous tissue disorders Alopecia	8.0% 4/50 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All 53 patients enrolled to the trial were monitored for mortality, the 50 treated patients were monitored for adverse events.
Skin and subcutaneous tissue disorders Dry skin	12.0% 6/50 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All 53 patients enrolled to the trial were monitored for mortality, the 50 treated patients were monitored for adverse events.
Skin and subcutaneous tissue disorders Pruritus	16.0% 8/50 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All 53 patients enrolled to the trial were monitored for mortality, the 50 treated patients were monitored for adverse events.
Skin and subcutaneous tissue disorders Rash acneiform	54.0% 27/50 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All 53 patients enrolled to the trial were monitored for mortality, the 50 treated patients were monitored for adverse events.
Skin and subcutaneous tissue disorders Rash maculo-papular	18.0% 9/50 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All 53 patients enrolled to the trial were monitored for mortality, the 50 treated patients were monitored for adverse events.
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, specify	8.0% 4/50 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All 53 patients enrolled to the trial were monitored for mortality, the 50 treated patients were monitored for adverse events.
Gastrointestinal disorders Constipation	12.0% 6/50 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All 53 patients enrolled to the trial were monitored for mortality, the 50 treated patients were monitored for adverse events.
Gastrointestinal disorders Diarrhea	52.0% 26/50 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All 53 patients enrolled to the trial were monitored for mortality, the 50 treated patients were monitored for adverse events.
Gastrointestinal disorders Mucositis oral	14.0% 7/50 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All 53 patients enrolled to the trial were monitored for mortality, the 50 treated patients were monitored for adverse events.
Gastrointestinal disorders Nausea	30.0% 15/50 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All 53 patients enrolled to the trial were monitored for mortality, the 50 treated patients were monitored for adverse events.
Gastrointestinal disorders Vomiting	18.0% 9/50 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All 53 patients enrolled to the trial were monitored for mortality, the 50 treated patients were monitored for adverse events.
Investigations Alanine aminotransferase increased	16.0% 8/50 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All 53 patients enrolled to the trial were monitored for mortality, the 50 treated patients were monitored for adverse events.
Investigations Alkaline phosphatase increased	18.0% 9/50 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All 53 patients enrolled to the trial were monitored for mortality, the 50 treated patients were monitored for adverse events.
Investigations Aspartate aminotransferase increased	34.0% 17/50 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All 53 patients enrolled to the trial were monitored for mortality, the 50 treated patients were monitored for adverse events.
Investigations CPK increased	32.0% 16/50 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All 53 patients enrolled to the trial were monitored for mortality, the 50 treated patients were monitored for adverse events.
Investigations Creatinine increased	8.0% 4/50 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All 53 patients enrolled to the trial were monitored for mortality, the 50 treated patients were monitored for adverse events.
Investigations Lymphocyte count decreased	8.0% 4/50 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All 53 patients enrolled to the trial were monitored for mortality, the 50 treated patients were monitored for adverse events.
Investigations Neutrophil count decreased	6.0% 3/50 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All 53 patients enrolled to the trial were monitored for mortality, the 50 treated patients were monitored for adverse events.
Investigations Platelet count decreased	12.0% 6/50 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All 53 patients enrolled to the trial were monitored for mortality, the 50 treated patients were monitored for adverse events.
Investigations White blood cell decreased	6.0% 3/50 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All 53 patients enrolled to the trial were monitored for mortality, the 50 treated patients were monitored for adverse events.
Metabolism and nutrition disorders Anorexia	10.0% 5/50 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All 53 patients enrolled to the trial were monitored for mortality, the 50 treated patients were monitored for adverse events.
Metabolism and nutrition disorders Hyperglycemia	6.0% 3/50 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All 53 patients enrolled to the trial were monitored for mortality, the 50 treated patients were monitored for adverse events.
Metabolism and nutrition disorders Hypoalbuminemia	14.0% 7/50 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All 53 patients enrolled to the trial were monitored for mortality, the 50 treated patients were monitored for adverse events.
Metabolism and nutrition disorders Hypocalcemia	6.0% 3/50 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All 53 patients enrolled to the trial were monitored for mortality, the 50 treated patients were monitored for adverse events.
Metabolism and nutrition disorders Hypomagnesemia	12.0% 6/50 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All 53 patients enrolled to the trial were monitored for mortality, the 50 treated patients were monitored for adverse events.
Musculoskeletal and connective tissue disorders Myalgia	6.0% 3/50 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All 53 patients enrolled to the trial were monitored for mortality, the 50 treated patients were monitored for adverse events.
Eye disorders Blurred vision	18.0% 9/50 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All 53 patients enrolled to the trial were monitored for mortality, the 50 treated patients were monitored for adverse events.
Eye disorders Retinal detachment	6.0% 3/50 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All 53 patients enrolled to the trial were monitored for mortality, the 50 treated patients were monitored for adverse events.
Eye disorders Eye disorders - Other, specify	14.0% 7/50 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All 53 patients enrolled to the trial were monitored for mortality, the 50 treated patients were monitored for adverse events.
Respiratory, thoracic and mediastinal disorders Cough	6.0% 3/50 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All 53 patients enrolled to the trial were monitored for mortality, the 50 treated patients were monitored for adverse events.
Respiratory, thoracic and mediastinal disorders Dyspnea	6.0% 3/50 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All 53 patients enrolled to the trial were monitored for mortality, the 50 treated patients were monitored for adverse events.
Vascular disorders Hypertension	10.0% 5/50 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All 53 patients enrolled to the trial were monitored for mortality, the 50 treated patients were monitored for adverse events.

Additional Information

Study Statistician

ECOG-ACRIN Statistical Office

Phone: 617-632-3012

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60