Trial Outcomes & Findings for Testing Treatment With Encorafenib and Binimetinib Before Surgery for Melanoma With Lymph Node Involvement (NCT NCT04221438)

Results Overview

Pathologic complete response (pCR) is defined as complete absence of viable tumor in the treated tumor bed. Partial pathologic response (pPR) is defined as less than or equal to 50% of the treated tumor bed is occupied by viable tumor cells. Pathologic non-response is defined as great than 50% of the treated tumor bed is occupied by viable tumor cells.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

3 participants

Primary outcome timeframe

Assessed at 10-12 weeks

Results posted on

2025-11-12

Participant Flow

The study was activated on February 18, 2020 and the first patient was enrolled in September, 2021. The study was closed on September 23, 2022 due to slow accrual.

Participant milestones

Participant milestones
Measure	Experimental: Neoadjuvant encorafenib + binimetinib, surgery, adjuvant encorafenib + binimetinib NEOADJUVANT TREATMENT: Patients receive 18F-FLT IV and undergo a PET/CT scan approximately 60 minutes later. Within 2 weeks, patients receive encorafenib PO QD and binimetinib PO BID on days 1-28. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive 18F-FLT IV and undergo a second PET/CT scan approximately 60 minutes later. SURGICAL RESECTION: Within 2 weeks of completing therapy with encorafenib and binimetinib, patients undergo surgery. ADJUVANT TREATMENT: Within 2-7 days after surgery, patients resume treatment with encorafenib PO QD and binimetinib PO BID on days 1-28. Treatment repeats every 28 days for up to 11 cycles in the absence of disease progression or unacceptable toxicity.
Overall Study STARTED	3
Overall Study Eligible and treated	3
Overall Study COMPLETED	1
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Experimental: Neoadjuvant encorafenib + binimetinib, surgery, adjuvant encorafenib + binimetinib NEOADJUVANT TREATMENT: Patients receive 18F-FLT IV and undergo a PET/CT scan approximately 60 minutes later. Within 2 weeks, patients receive encorafenib PO QD and binimetinib PO BID on days 1-28. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive 18F-FLT IV and undergo a second PET/CT scan approximately 60 minutes later. SURGICAL RESECTION: Within 2 weeks of completing therapy with encorafenib and binimetinib, patients undergo surgery. ADJUVANT TREATMENT: Within 2-7 days after surgery, patients resume treatment with encorafenib PO QD and binimetinib PO BID on days 1-28. Treatment repeats every 28 days for up to 11 cycles in the absence of disease progression or unacceptable toxicity.
Overall Study Adverse Event	1
Overall Study No surgery within required timeframe due to Covid diagnosis	1

Baseline Characteristics

Testing Treatment With Encorafenib and Binimetinib Before Surgery for Melanoma With Lymph Node Involvement

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Neoadjuvant Encorafenib + Binimetinib, Surgery, Adjuvant Encorafenib + Binimetinib n=3 Participants NEOADJUVANT TREATMENT: Patients receive 18F-FLT IV and undergo a PET/CT scan approximately 60 minutes later. Within 2 weeks, patients receive encorafenib PO QD and binimetinib PO BID on days 1-28. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive 18F-FLT IV and undergo a second PET/CT scan approximately 60 minutes later. SURGICAL RESECTION: Within 2 weeks of completing therapy with encorafenib and binimetinib, patients undergo surgery. ADJUVANT TREATMENT: Within 2-7 days after surgery, patients resume treatment with encorafenib PO QD and binimetinib PO BID on days 1-28. Treatment repeats every 28 days for up to 11 cycles in the absence of disease progression or unacceptable toxicity.
Age, Continuous	42 years n=10 Participants
Sex: Female, Male Female	2 Participants n=10 Participants
Sex: Female, Male Male	1 Participants n=10 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=10 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=10 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=10 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=10 Participants
Race (NIH/OMB) Asian	0 Participants n=10 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=10 Participants
Race (NIH/OMB) Black or African American	0 Participants n=10 Participants
Race (NIH/OMB) White	3 Participants n=10 Participants
Race (NIH/OMB) More than one race	0 Participants n=10 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=10 Participants

PRIMARY outcome

Timeframe: Assessed at 10-12 weeks

Population: All 3 enrolled patients are included in this analysis

Pathologic complete response (pCR) is defined as complete absence of viable tumor in the treated tumor bed. Partial pathologic response (pPR) is defined as less than or equal to 50% of the treated tumor bed is occupied by viable tumor cells. Pathologic non-response is defined as great than 50% of the treated tumor bed is occupied by viable tumor cells.

Outcome measures

Outcome measures
Measure	Neoadjuvant encorafenib + binimetinib, surgery, adjuvant encorafenib + binimetinib n=3 Participants NEOADJUVANT TREATMENT: Patients receive 18F-FLT IV and undergo a PET/CT scan approximately 60 minutes later. Within 2 weeks, patients receive encorafenib PO QD and binimetinib PO BID on days 1-28. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive 18F-FLT IV and undergo a second PET/CT scan approximately 60 minutes later. SURGICAL RESECTION: Within 2 weeks of completing therapy with encorafenib and binimetinib, patients undergo surgery. ADJUVANT TREATMENT: Within 2-7 days after surgery, patients resume treatment with encorafenib PO QD and binimetinib PO BID on days 1-28. Treatment repeats every 28 days for up to 11 cycles in the absence of disease progression or unacceptable toxicity.	Patients without pCR Patients without pathologic complete response
Pathologic Complete Response Pathologic complete response	2 Participants	—
Pathologic Complete Response Pathologic partial response	1 Participants	—

SECONDARY outcome

Timeframe: Assessed at baseline, 8 weeks, then every 12 weeks up to 1.4 years

Population: All 3 enrolled patients are included in this analysis

Objective response is defined as either complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). Complete response is defined as disappearance of all lesions. Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters and/or persistence of one or more non-target lesion(s). Stable disease is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters while on study. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study or appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.

Outcome measures

Outcome measures
Measure	Neoadjuvant encorafenib + binimetinib, surgery, adjuvant encorafenib + binimetinib n=3 Participants NEOADJUVANT TREATMENT: Patients receive 18F-FLT IV and undergo a PET/CT scan approximately 60 minutes later. Within 2 weeks, patients receive encorafenib PO QD and binimetinib PO BID on days 1-28. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive 18F-FLT IV and undergo a second PET/CT scan approximately 60 minutes later. SURGICAL RESECTION: Within 2 weeks of completing therapy with encorafenib and binimetinib, patients undergo surgery. ADJUVANT TREATMENT: Within 2-7 days after surgery, patients resume treatment with encorafenib PO QD and binimetinib PO BID on days 1-28. Treatment repeats every 28 days for up to 11 cycles in the absence of disease progression or unacceptable toxicity.	Patients without pCR Patients without pathologic complete response
Objective Response partial response	2 Participants	—
Objective Response stable disease	1 Participants	—

SECONDARY outcome

Timeframe: Assessed at baseline, 8 weeks, then every 12 weeks up to 19.4 months

Population: All 3 patients enrolled were included.

Disease-free survival is defined as the time from date of surgical resection to the date of recurrence or death, whichever occurs first. Recurrence must be documented by radiologic exams and with biopsy in all cases except for brain metastases (biopsy not required). Abnormal blood studies alone (e.g., elevated transaminases or alkaline phosphatase) are not sufficient evidence of relapse. Whenever possible, histologic proof of recurrence should be obtained unless the lesion is not accessible or a biopsy would cause undue risk to the patient.

Outcome measures

Outcome measures
Measure	Neoadjuvant encorafenib + binimetinib, surgery, adjuvant encorafenib + binimetinib n=3 Participants NEOADJUVANT TREATMENT: Patients receive 18F-FLT IV and undergo a PET/CT scan approximately 60 minutes later. Within 2 weeks, patients receive encorafenib PO QD and binimetinib PO BID on days 1-28. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive 18F-FLT IV and undergo a second PET/CT scan approximately 60 minutes later. SURGICAL RESECTION: Within 2 weeks of completing therapy with encorafenib and binimetinib, patients undergo surgery. ADJUVANT TREATMENT: Within 2-7 days after surgery, patients resume treatment with encorafenib PO QD and binimetinib PO BID on days 1-28. Treatment repeats every 28 days for up to 11 cycles in the absence of disease progression or unacceptable toxicity.	Patients without pCR Patients without pathologic complete response
Disease-free Survival	13.1 months Interval 8.3 to 19.4	—

SECONDARY outcome

Timeframe: Assessed at every 3 months for 2 years and then every 6 months, up to 2 years 9 months

Population: All 3 enrolled patients are included in this analysis. All 3 patients were alive as of this analysis.

Overall survival is defined as the time from registration to death or date last known alive, which is the censoring date for patients who are still alive.

Outcome measures

Outcome measures
Measure	Neoadjuvant encorafenib + binimetinib, surgery, adjuvant encorafenib + binimetinib n=3 Participants NEOADJUVANT TREATMENT: Patients receive 18F-FLT IV and undergo a PET/CT scan approximately 60 minutes later. Within 2 weeks, patients receive encorafenib PO QD and binimetinib PO BID on days 1-28. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive 18F-FLT IV and undergo a second PET/CT scan approximately 60 minutes later. SURGICAL RESECTION: Within 2 weeks of completing therapy with encorafenib and binimetinib, patients undergo surgery. ADJUVANT TREATMENT: Within 2-7 days after surgery, patients resume treatment with encorafenib PO QD and binimetinib PO BID on days 1-28. Treatment repeats every 28 days for up to 11 cycles in the absence of disease progression or unacceptable toxicity.	Patients without pCR Patients without pathologic complete response
Overall Survival	24 months Interval 21.8 to 28.5	—

SECONDARY outcome

Timeframe: Assessed at baseline, 8 weeks, then every 12 weeks up to 1.4 years

Population: All enrolled patients are included in this analysis.

Association between pCR and best response will be reported.

Outcome measures

Outcome measures
Measure	Neoadjuvant encorafenib + binimetinib, surgery, adjuvant encorafenib + binimetinib n=2 Participants NEOADJUVANT TREATMENT: Patients receive 18F-FLT IV and undergo a PET/CT scan approximately 60 minutes later. Within 2 weeks, patients receive encorafenib PO QD and binimetinib PO BID on days 1-28. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive 18F-FLT IV and undergo a second PET/CT scan approximately 60 minutes later. SURGICAL RESECTION: Within 2 weeks of completing therapy with encorafenib and binimetinib, patients undergo surgery. ADJUVANT TREATMENT: Within 2-7 days after surgery, patients resume treatment with encorafenib PO QD and binimetinib PO BID on days 1-28. Treatment repeats every 28 days for up to 11 cycles in the absence of disease progression or unacceptable toxicity.	Patients without pCR n=1 Participants Patients without pathologic complete response
Associations Between pCR and Best Response Partial Response	1 Participants	1 Participants
Associations Between pCR and Best Response Stable Disease	1 Participants	0 Participants

Adverse Events

Experimental: Neoadjuvant encorafenib + binimetinib, surgery, adjuvant encorafenib + binimetinib

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Experimental: Neoadjuvant encorafenib + binimetinib, surgery, adjuvant encorafenib + binimetinib n=3 participants at risk NEOADJUVANT TREATMENT: Patients receive 18F-FLT IV and undergo a PET/CT scan approximately 60 minutes later. Within 2 weeks, patients receive encorafenib PO QD and binimetinib PO BID on days 1-28. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive 18F-FLT IV and undergo a second PET/CT scan approximately 60 minutes later. SURGICAL RESECTION: Within 2 weeks of completing therapy with encorafenib and binimetinib, patients undergo surgery. ADJUVANT TREATMENT: Within 2-7 days after surgery, patients resume treatment with encorafenib PO QD and binimetinib PO BID on days 1-28. Treatment repeats every 28 days for up to 11 cycles in the absence of disease progression or unacceptable toxicity.
Surgical and medical procedures Surgical and medical procedures - Other, specify	33.3% 1/3 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 2 years and 9 months All 3 patients enrolled are included in the analysis of adverse events and all-cause mortality. As of this analysis, no patients had died.

Other adverse events

Other adverse events
Measure	Experimental: Neoadjuvant encorafenib + binimetinib, surgery, adjuvant encorafenib + binimetinib n=3 participants at risk NEOADJUVANT TREATMENT: Patients receive 18F-FLT IV and undergo a PET/CT scan approximately 60 minutes later. Within 2 weeks, patients receive encorafenib PO QD and binimetinib PO BID on days 1-28. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive 18F-FLT IV and undergo a second PET/CT scan approximately 60 minutes later. SURGICAL RESECTION: Within 2 weeks of completing therapy with encorafenib and binimetinib, patients undergo surgery. ADJUVANT TREATMENT: Within 2-7 days after surgery, patients resume treatment with encorafenib PO QD and binimetinib PO BID on days 1-28. Treatment repeats every 28 days for up to 11 cycles in the absence of disease progression or unacceptable toxicity.
Investigations Aspartate aminotransferase increased	33.3% 1/3 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 2 years and 9 months All 3 patients enrolled are included in the analysis of adverse events and all-cause mortality. As of this analysis, no patients had died.
Investigations CPK increased	33.3% 1/3 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 2 years and 9 months All 3 patients enrolled are included in the analysis of adverse events and all-cause mortality. As of this analysis, no patients had died.
Investigations Creatinine increased	33.3% 1/3 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 2 years and 9 months All 3 patients enrolled are included in the analysis of adverse events and all-cause mortality. As of this analysis, no patients had died.
Musculoskeletal and connective tissue disorders Myalgia	33.3% 1/3 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 2 years and 9 months All 3 patients enrolled are included in the analysis of adverse events and all-cause mortality. As of this analysis, no patients had died.
Musculoskeletal and connective tissue disorders Pain in extremity	33.3% 1/3 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 2 years and 9 months All 3 patients enrolled are included in the analysis of adverse events and all-cause mortality. As of this analysis, no patients had died.
Vascular disorders Hypotension	33.3% 1/3 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 2 years and 9 months All 3 patients enrolled are included in the analysis of adverse events and all-cause mortality. As of this analysis, no patients had died.
Blood and lymphatic system disorders Blood and lymphatic system disorders - Other, specify	33.3% 1/3 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 2 years and 9 months All 3 patients enrolled are included in the analysis of adverse events and all-cause mortality. As of this analysis, no patients had died.
Cardiac disorders Cardiac disorders - Other, specify	33.3% 1/3 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 2 years and 9 months All 3 patients enrolled are included in the analysis of adverse events and all-cause mortality. As of this analysis, no patients had died.
General disorders and administration site conditions Edema limbs	33.3% 1/3 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 2 years and 9 months All 3 patients enrolled are included in the analysis of adverse events and all-cause mortality. As of this analysis, no patients had died.
General disorders and administration site conditions Fatigue	33.3% 1/3 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 2 years and 9 months All 3 patients enrolled are included in the analysis of adverse events and all-cause mortality. As of this analysis, no patients had died.
Gastrointestinal disorders Abdominal pain	33.3% 1/3 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 2 years and 9 months All 3 patients enrolled are included in the analysis of adverse events and all-cause mortality. As of this analysis, no patients had died.
Gastrointestinal disorders Diarrhea	100.0% 3/3 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 2 years and 9 months All 3 patients enrolled are included in the analysis of adverse events and all-cause mortality. As of this analysis, no patients had died.
Gastrointestinal disorders Nausea	33.3% 1/3 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 2 years and 9 months All 3 patients enrolled are included in the analysis of adverse events and all-cause mortality. As of this analysis, no patients had died.
Infections and infestations Soft tissue infection	33.3% 1/3 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 2 years and 9 months All 3 patients enrolled are included in the analysis of adverse events and all-cause mortality. As of this analysis, no patients had died.
Investigations Alanine aminotransferase increased	33.3% 1/3 • Assessed every 4 weeks while on treatment and for 30 days after the end of treatment, up to 2 years and 9 months All 3 patients enrolled are included in the analysis of adverse events and all-cause mortality. As of this analysis, no patients had died.

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