Trial Outcomes & Findings for Testing VS-6063 (Defactinib) as a Potential Targeted Treatment in Cancers With NF2 Genetic Changes (MATCH-Subprotocol U) (NCT NCT04439331)

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 analyzable patients. Objective response is defined consistent with 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. Details about how to define complete response and partial response can be found in the master protocol. 90% two-sided binomial exact confidence interval is calculated for ORR.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE2

Target enrollment

35 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 U was activated on August 12, 2015. Thirty-five patients were enrolled on EAY131-U between November 19, 2015, and November 8, 2017. Twenty-seven patients were enrolled on the basis of the results from the NCI-MATCH assay and 8 on the basis of the outside assay results.

Patients whose tumors harbored an inactivating NF2 mutation on next-generation sequencing were assigned to sub-protocol U. The mutation status was determined by an NCI-MATCH approved laboratory for 8 patients in this arm, these cases had to be confirmed to be used in primary analysis.

Participant milestones

Participant milestones
Measure	Treatment (Defactinib) Patients receive defactinib PO 400 mg BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Overall Study STARTED	35
Overall Study Started Protocol Therapy	33
Overall Study Eligible, Treated and Mutation Status Confirmed	30
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	35

Reasons for withdrawal

Reasons for withdrawal
Measure	Treatment (Defactinib) Patients receive defactinib PO 400 mg BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Overall Study Never Start Protocol Therapy	2
Overall Study Ineligible	2
Overall Study Mutation Status Not Confirmed	1
Overall Study Adverse Event	1
Overall Study Death	1
Overall Study Disease Progression	20
Overall Study Withdrawal by Subject	6
Overall Study Physician Decision	1
Overall Study Other Complicating Disease	1

Baseline Characteristics

Testing VS-6063 (Defactinib) as a Potential Targeted Treatment in Cancers With NF2 Genetic Changes (MATCH-Subprotocol U)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment (Defactinib) n=30 Participants Patients receive defactinib PO 400 mg BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Age, Continuous	61 years
Sex: Female, Male Female	20 Participants
Sex: Female, Male Male	10 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	2 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	27 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	0 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	25 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: Eligible, treated and mutation status confirmed

Outcome measures

Outcome measures
Measure	Treatment (Defactinib) n=30 Participants Patients receive defactinib PO 400 mg BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Objective Response Rate (ORR)	3.2 percentage of participants Interval 0.17 to 14.9

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: Eligible, treated and mutation status confirmed

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 (Defactinib) n=30 Participants Patients receive defactinib PO 400 mg BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
6-month Progression Free Survival (PFS)	22.8 percentage of participants Interval 11.2 to 36.7

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: Eligible, treated and mutation status confirmed

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 (Defactinib) n=30 Participants Patients receive defactinib PO 400 mg BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Progression Free Survival	1.9 months Interval 1.8 to 3.6

Adverse Events

Treatment (Defactinib)

Serious events: 9 serious events

Other events: 22 other events

Deaths: 29 deaths

Serious adverse events

Serious adverse events
Measure	Treatment (Defactinib) n=33 participants at risk Patients receive defactinib PO 400 mg BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Ear and labyrinth disorders Ear and labyrinth disorders - Other, specify	3.0% 1/33 • 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. Thirty-three patients were included in the toxicity analysis (excluding two who did not receive treatment).
Blood and lymphatic system disorders Anemia	3.0% 1/33 • 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. Thirty-three patients were included in the toxicity analysis (excluding two who did not receive treatment).
General disorders Fatigue	12.1% 4/33 • 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. Thirty-three patients were included in the toxicity analysis (excluding two who did not receive treatment).
Gastrointestinal disorders Abdominal pain	3.0% 1/33 • 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. Thirty-three patients were included in the toxicity analysis (excluding two who did not receive treatment).
Gastrointestinal disorders Nausea	3.0% 1/33 • 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. Thirty-three patients were included in the toxicity analysis (excluding two who did not receive treatment).
Investigations Alanine aminotransferase increased	3.0% 1/33 • 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. Thirty-three patients were included in the toxicity analysis (excluding two who did not receive treatment).
Investigations Aspartate aminotransferase increased	3.0% 1/33 • 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. Thirty-three patients were included in the toxicity analysis (excluding two who did not receive treatment).
Metabolism and nutrition disorders Dehydration	3.0% 1/33 • 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. Thirty-three patients were included in the toxicity analysis (excluding two who did not receive treatment).
Musculoskeletal and connective tissue disorders Back pain	3.0% 1/33 • 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. Thirty-three patients were included in the toxicity analysis (excluding two who did not receive treatment).
Musculoskeletal and connective tissue disorders Pain in extremity	3.0% 1/33 • 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. Thirty-three patients were included in the toxicity analysis (excluding two who did not receive treatment).
Nervous system disorders Headache	3.0% 1/33 • 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. Thirty-three patients were included in the toxicity analysis (excluding two who did not receive treatment).
Nervous system disorders Syncope	3.0% 1/33 • 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. Thirty-three patients were included in the toxicity analysis (excluding two who did not receive treatment).
Vascular disorders Hypertension	3.0% 1/33 • 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. Thirty-three patients were included in the toxicity analysis (excluding two who did not receive treatment).

Other adverse events

Other adverse events
Measure	Treatment (Defactinib) n=33 participants at risk Patients receive defactinib PO 400 mg BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Blood and lymphatic system disorders Anemia	18.2% 6/33 • 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. Thirty-three patients were included in the toxicity analysis (excluding two who did not receive treatment).
General disorders Edema limbs	12.1% 4/33 • 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. Thirty-three patients were included in the toxicity analysis (excluding two who did not receive treatment).
General disorders Fatigue	33.3% 11/33 • 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. Thirty-three patients were included in the toxicity analysis (excluding two who did not receive treatment).
Gastrointestinal disorders Diarrhea	18.2% 6/33 • 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. Thirty-three patients were included in the toxicity analysis (excluding two who did not receive treatment).
Gastrointestinal disorders Nausea	30.3% 10/33 • 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. Thirty-three patients were included in the toxicity analysis (excluding two who did not receive treatment).
Gastrointestinal disorders Stomach pain	6.1% 2/33 • 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. Thirty-three patients were included in the toxicity analysis (excluding two who did not receive treatment).
Gastrointestinal disorders Vomiting	15.2% 5/33 • 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. Thirty-three patients were included in the toxicity analysis (excluding two who did not receive treatment).
Investigations Alkaline phosphatase increased	6.1% 2/33 • 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. Thirty-three patients were included in the toxicity analysis (excluding two who did not receive treatment).
Investigations Aspartate aminotransferase increased	9.1% 3/33 • 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. Thirty-three patients were included in the toxicity analysis (excluding two who did not receive treatment).
Investigations Blood bilirubin increased	27.3% 9/33 • 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. Thirty-three patients were included in the toxicity analysis (excluding two who did not receive treatment).
Investigations Lymphocyte count decreased	9.1% 3/33 • 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. Thirty-three patients were included in the toxicity analysis (excluding two who did not receive treatment).
Investigations White blood cell decreased	6.1% 2/33 • 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. Thirty-three patients were included in the toxicity analysis (excluding two who did not receive treatment).
Metabolism and nutrition disorders Anorexia	12.1% 4/33 • 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. Thirty-three patients were included in the toxicity analysis (excluding two who did not receive treatment).
Metabolism and nutrition disorders Hyperglycemia	6.1% 2/33 • 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. Thirty-three patients were included in the toxicity analysis (excluding two who did not receive treatment).
Metabolism and nutrition disorders Hypoalbuminemia	6.1% 2/33 • 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. Thirty-three patients were included in the toxicity analysis (excluding two who did not receive treatment).
Metabolism and nutrition disorders Hypocalcemia	6.1% 2/33 • 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. Thirty-three patients were included in the toxicity analysis (excluding two who did not receive treatment).
Metabolism and nutrition disorders Hypomagnesemia	6.1% 2/33 • 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. Thirty-three patients were included in the toxicity analysis (excluding two who did not receive treatment).
Musculoskeletal and connective tissue disorders Generalized muscle weakness	9.1% 3/33 • 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. Thirty-three patients were included in the toxicity analysis (excluding two who did not receive treatment).
Nervous system disorders Dizziness	9.1% 3/33 • 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. Thirty-three patients were included in the toxicity analysis (excluding two who did not receive treatment).
Nervous system disorders Headache	6.1% 2/33 • 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. Thirty-three patients were included in the toxicity analysis (excluding two who did not receive treatment).
Psychiatric disorders Confusion	9.1% 3/33 • 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. Thirty-three patients were included in the toxicity analysis (excluding two who did not receive treatment).
Psychiatric disorders Insomnia	6.1% 2/33 • 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. Thirty-three patients were included in the toxicity analysis (excluding two who did not receive treatment).
Respiratory, thoracic and mediastinal disorders Cough	9.1% 3/33 • 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. Thirty-three patients were included in the toxicity analysis (excluding two who did not receive treatment).
Respiratory, thoracic and mediastinal disorders Dyspnea	9.1% 3/33 • 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. Thirty-three patients were included in the toxicity analysis (excluding two who did not receive treatment).
Renal and urinary disorders Hematuria	6.1% 2/33 • 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. Thirty-three patients were included in the toxicity analysis (excluding two who did not receive treatment).
Renal and urinary disorders Proteinuria	6.1% 2/33 • 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. Thirty-three patients were included in the toxicity analysis (excluding two who did not receive treatment).

Additional Information

Study Statistician

ECOG-ACRIN Cancer Research Group

Phone: 617-632-3012

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60