Trial Outcomes & Findings for Testing Trametinib as a Potential Targeted Treatment in Cancers With NF1 Genetic Changes (MATCH-Subprotocol S1) (NCT NCT04439318)

Last Updated: 2025-08-07

Results Overview

Overall response rate was defined as the proportion of patients with best overall response of complete response (CR) or partial response (PR) among all eligible and treated patients. Best overall response 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. Please refer to the protocol for the detailed definitions of response criteria. The 90% two-sided binomial exact confidence interval was calculated for ORR.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE2

Target enrollment

50 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

2025-08-07

Participant Flow

Eighty-one patients were assigned to Subprotocol S1 after screening, all from screening cohort. Of the 81 patients, 50 patients were enrolled in arm S1 between March 2016 and July 2017.

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 S1, patients had to have a qualifying NF1 actionable mutation.

Participant milestones

Participant milestones
Measure	Treatment (Trametinib) Patients receive trametinib dimethyl sulfoxide 2mg PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Overall Study STARTED	50
Overall Study Eligible	49
Overall Study Eligible and Started Protocol Therapy	46
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	50

Reasons for withdrawal

Reasons for withdrawal
Measure	Treatment (Trametinib) Patients receive trametinib dimethyl sulfoxide 2mg PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Overall Study Ineligible	1
Overall Study Never Started Treatment	3
Overall Study Adverse Event	10
Overall Study Death	2
Overall Study Disease Progression	25
Overall Study Other Complicating Disease	2
Overall Study Withdrawal by Subject	4
Overall Study Patient Refusal - Prefers Different Therapy	1
Overall Study Non-Compliance	1
Overall Study Still on Treatment	1

Baseline Characteristics

Testing Trametinib as a Potential Targeted Treatment in Cancers With NF1 Genetic Changes (MATCH-Subprotocol S1)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment (Trametinib) n=46 Participants Patients receive trametinib dimethyl sulfoxide 2mg PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Age, Continuous	60 years n=5 Participants
Sex: Female, Male Female	27 Participants n=5 Participants
Sex: Female, Male Male	19 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	40 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	5 Participants n=5 Participants
Race (NIH/OMB) White	37 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=5 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 (Trametinib) n=46 Participants Patients receive trametinib dimethyl sulfoxide 2mg PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Objective Response Rate (ORR)	4.3 percentage of participants Interval 0.8 to 13.1

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, from which 6-month PFS rate 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. Please refer to the protocol for detailed definitions of disease progression. 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 (Trametinib) n=46 Participants Patients receive trametinib dimethyl sulfoxide 2mg PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
6-month Progression-free Survival (PFS) Rate	21 percentage of participants Interval 12.0 to 34.0

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

PFS was defined as time from treatment start date to date of disease progression or death from any causes, whichever occurred first. Median PFS was estimated using the Kaplan-Meier method. 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. Please refer to the protocol for detailed definitions of disease progression.

Outcome measures

Outcome measures
Measure	Treatment (Trametinib) n=46 Participants Patients receive trametinib dimethyl sulfoxide 2mg PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Progression Free Survival (PFS)	1.9 months Interval 1.8 to 3.5

Adverse Events

Treatment (Trametinib)

Serious events: 20 serious events

Other events: 36 other events

Deaths: 38 deaths

Serious adverse events

Serious adverse events
Measure	Treatment (Trametinib) n=47 participants at risk Patients receive trametinib dimethyl sulfoxide 2mg PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Cardiac disorders Heart failure	2.1% 1/47 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Forty-seven patients were included in the toxicity analysis (excluding three who did not receive protocol treatment).
General disorders Edema limbs	2.1% 1/47 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Forty-seven patients were included in the toxicity analysis (excluding three who did not receive protocol treatment).
General disorders Fatigue	10.6% 5/47 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Forty-seven patients were included in the toxicity analysis (excluding three who did not receive protocol treatment).
General disorders Sudden death NOS	2.1% 1/47 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Forty-seven patients were included in the toxicity analysis (excluding three who did not receive protocol treatment).
Skin and subcutaneous tissue disorders Pruritus	2.1% 1/47 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Forty-seven patients were included in the toxicity analysis (excluding three who did not receive protocol treatment).
Skin and subcutaneous tissue disorders Rash acneiform	2.1% 1/47 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Forty-seven patients were included in the toxicity analysis (excluding three who did not receive protocol treatment).
Skin and subcutaneous tissue disorders Rash maculo-papular	2.1% 1/47 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Forty-seven patients were included in the toxicity analysis (excluding three who did not receive protocol treatment).
Gastrointestinal disorders Mucositis oral	6.4% 3/47 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Forty-seven patients were included in the toxicity analysis (excluding three who did not receive protocol treatment).
Gastrointestinal disorders Nausea	2.1% 1/47 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Forty-seven patients were included in the toxicity analysis (excluding three who did not receive protocol treatment).
Gastrointestinal disorders Vomiting	4.3% 2/47 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Forty-seven patients were included in the toxicity analysis (excluding three who did not receive protocol treatment).
Gastrointestinal disorders Gastrointestinal disorders - Other, specify	2.1% 1/47 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Forty-seven patients were included in the toxicity analysis (excluding three who did not receive protocol treatment).
Immune system disorders Allergic reaction	2.1% 1/47 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Forty-seven patients were included in the toxicity analysis (excluding three who did not receive protocol treatment).
Investigations Alanine aminotransferase increased	2.1% 1/47 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Forty-seven patients were included in the toxicity analysis (excluding three who did not receive protocol treatment).
Investigations Aspartate aminotransferase increased	4.3% 2/47 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Forty-seven patients were included in the toxicity analysis (excluding three who did not receive protocol treatment).
Investigations Blood bilirubin increased	2.1% 1/47 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Forty-seven patients were included in the toxicity analysis (excluding three who did not receive protocol treatment).
Metabolism and nutrition disorders Hypokalemia	2.1% 1/47 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Forty-seven patients were included in the toxicity analysis (excluding three who did not receive protocol treatment).
Musculoskeletal and connective tissue disorders Generalized muscle weakness	2.1% 1/47 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Forty-seven patients were included in the toxicity analysis (excluding three who did not receive protocol treatment).
Musculoskeletal and connective tissue disorders Muscle weakness lower limb	2.1% 1/47 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Forty-seven patients were included in the toxicity analysis (excluding three who did not receive protocol treatment).
Musculoskeletal and connective tissue disorders Muscle weakness upper limb	2.1% 1/47 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Forty-seven patients were included in the toxicity analysis (excluding three who did not receive protocol treatment).
Musculoskeletal and connective tissue disorders Myalgia	2.1% 1/47 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Forty-seven patients were included in the toxicity analysis (excluding three who did not receive protocol treatment).
Musculoskeletal and connective tissue disorders Myositis	2.1% 1/47 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Forty-seven patients were included in the toxicity analysis (excluding three who did not receive protocol treatment).
Nervous system disorders Syncope	2.1% 1/47 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Forty-seven patients were included in the toxicity analysis (excluding three who did not receive protocol treatment).
Respiratory, thoracic and mediastinal disorders Dyspnea	4.3% 2/47 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Forty-seven patients were included in the toxicity analysis (excluding three who did not receive protocol treatment).
Vascular disorders Hypertension	4.3% 2/47 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Forty-seven patients were included in the toxicity analysis (excluding three who did not receive protocol treatment).

Other adverse events

Other adverse events
Measure	Treatment (Trametinib) n=47 participants at risk Patients receive trametinib dimethyl sulfoxide 2mg PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Blood and lymphatic system disorders Anemia	19.1% 9/47 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Forty-seven patients were included in the toxicity analysis (excluding three who did not receive protocol treatment).
General disorders Edema face	6.4% 3/47 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Forty-seven patients were included in the toxicity analysis (excluding three who did not receive protocol treatment).
General disorders Edema limbs	17.0% 8/47 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Forty-seven patients were included in the toxicity analysis (excluding three who did not receive protocol treatment).
General disorders Fatigue	31.9% 15/47 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Forty-seven patients were included in the toxicity analysis (excluding three who did not receive protocol treatment).
General disorders Pain	8.5% 4/47 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Forty-seven patients were included in the toxicity analysis (excluding three who did not receive protocol treatment).
Skin and subcutaneous tissue disorders Dry skin	17.0% 8/47 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Forty-seven patients were included in the toxicity analysis (excluding three who did not receive protocol treatment).
Skin and subcutaneous tissue disorders Pruritus	8.5% 4/47 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Forty-seven patients were included in the toxicity analysis (excluding three who did not receive protocol treatment).
Skin and subcutaneous tissue disorders Rash acneiform	40.4% 19/47 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Forty-seven patients were included in the toxicity analysis (excluding three who did not receive protocol treatment).
Skin and subcutaneous tissue disorders Rash maculo-papular	27.7% 13/47 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Forty-seven patients were included in the toxicity analysis (excluding three who did not receive protocol treatment).
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, specify	10.6% 5/47 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Forty-seven patients were included in the toxicity analysis (excluding three who did not receive protocol treatment).
Gastrointestinal disorders Constipation	8.5% 4/47 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Forty-seven patients were included in the toxicity analysis (excluding three who did not receive protocol treatment).
Gastrointestinal disorders Diarrhea	42.6% 20/47 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Forty-seven patients were included in the toxicity analysis (excluding three who did not receive protocol treatment).
Gastrointestinal disorders Dry mouth	10.6% 5/47 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Forty-seven patients were included in the toxicity analysis (excluding three who did not receive protocol treatment).
Gastrointestinal disorders Mucositis oral	12.8% 6/47 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Forty-seven patients were included in the toxicity analysis (excluding three who did not receive protocol treatment).
Gastrointestinal disorders Nausea	31.9% 15/47 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Forty-seven patients were included in the toxicity analysis (excluding three who did not receive protocol treatment).
Gastrointestinal disorders Vomiting	17.0% 8/47 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Forty-seven patients were included in the toxicity analysis (excluding three who did not receive protocol treatment).
Investigations Alanine aminotransferase increased	6.4% 3/47 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Forty-seven patients were included in the toxicity analysis (excluding three who did not receive protocol treatment).
Investigations Alkaline phosphatase increased	14.9% 7/47 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Forty-seven patients were included in the toxicity analysis (excluding three who did not receive protocol treatment).
Investigations Aspartate aminotransferase increased	21.3% 10/47 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Forty-seven patients were included in the toxicity analysis (excluding three who did not receive protocol treatment).
Metabolism and nutrition disorders Anorexia	6.4% 3/47 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Forty-seven patients were included in the toxicity analysis (excluding three who did not receive protocol treatment).
Metabolism and nutrition disorders Hyperglycemia	6.4% 3/47 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Forty-seven patients were included in the toxicity analysis (excluding three who did not receive protocol treatment).
Metabolism and nutrition disorders Hypoalbuminemia	6.4% 3/47 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Forty-seven patients were included in the toxicity analysis (excluding three who did not receive protocol treatment).
Metabolism and nutrition disorders Hypocalcemia	10.6% 5/47 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Forty-seven patients were included in the toxicity analysis (excluding three who did not receive protocol treatment).
Metabolism and nutrition disorders Hypokalemia	6.4% 3/47 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Forty-seven patients were included in the toxicity analysis (excluding three who did not receive protocol treatment).
Metabolism and nutrition disorders Hyponatremia	6.4% 3/47 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Forty-seven patients were included in the toxicity analysis (excluding three who did not receive protocol treatment).
Psychiatric disorders Insomnia	8.5% 4/47 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Forty-seven patients were included in the toxicity analysis (excluding three who did not receive protocol treatment).
Vascular disorders Hypertension	10.6% 5/47 • Assessed every 28 days while on treatment and for 30 days after the end of treatment, up to 3 years post registration. All patients enrolled were included in the all-cause mortality analysis. Forty-seven patients were included in the toxicity analysis (excluding three who did not receive protocol treatment).

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