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

NCT04221438 | Terminated Phase 2 Results FDA Drug

• 3 other identifiers: EA6183NCI-2019-07407U10CA180820
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 10

Brief Summary

This phase II trial studies how well encorafenib and binimetinib work before surgery in treating patients with BRAF V600-mutated stage IIIB-D melanoma that has spread to the lymph nodes. Encorafenib and binimetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. This trial also studies how well 18F-FLT positron emission tomography (PET)/computed tomography (CT) works in predicting the response of melanoma to encorafenib and binimetinib. 18F-FLT is an imaging agent, sometimes called a tracer. PET and CT are types of imaging scans. Using 18F-FLT PET/CT together with encorafenib and binimetinib may provide more information on melanoma over time.

Conditions

Melanoma of Unknown Primary; Metastatic Malignant Neoplasm in Lymph Node; Pathologic Stage IIIB Cutaneous Melanoma AJCC v8; Pathologic Stage IIIC Cutaneous Melanoma AJCC v8; Pathologic Stage IIID Cutaneous Melanoma AJCC v8; Recurrent Cutaneous Melanoma

Outcome Measures

Primary Outcomes (1)

• Pathologic Complete Response

  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.

  Assessed at 10-12 weeks

Secondary Outcomes (4)

• Objective Response

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

• Disease-free Survival

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

• Overall Survival

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

• Associations Between pCR and Best Response

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

Other Outcomes (6)

• CD8+ T Cell Infiltration and Ki-67 Status

  Assessed at baseline, during neoadjuvant treatment and at surgery

• Concordance Between Local Review for Pathologic Response and Central Pathology Review

  Assessed at surgery

• Change in 18F-FLT PET/CT Uptake

  Assessed at baseline and post-neoadjuvant therapy

Study Arms (1)

Neoadjuvant encorafenib + binimetinib, surgery, adjuvant encorafenib + binimetinib

EXPERIMENTAL

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.

Drug: Binimetinib; Procedure: Conventional Surgery; Drug: Encorafenib; Other: Fluorothymidine F-18

Interventions

Conventional Surgery PROCEDURE

Undergo surgery

Neoadjuvant encorafenib + binimetinib, surgery, adjuvant encorafenib + binimetinib

Encorafenib DRUG

Given PO

Also known as: ONO-7702, LGX818

Neoadjuvant encorafenib + binimetinib, surgery, adjuvant encorafenib + binimetinib

Fluorothymidine F-18 OTHER

Given IV

Also known as: 18F-FLT, 3'-deoxy-3'- 18F fluorothymidine, FLT

Neoadjuvant encorafenib + binimetinib, surgery, adjuvant encorafenib + binimetinib

Binimetinib DRUG

Given PO

Also known as: NSC 788187, ARRY-438162, MEK162, Mektovi

Neoadjuvant encorafenib + binimetinib, surgery, adjuvant encorafenib + binimetinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient must have histologically proven melanoma that is clinically evident (macroscopic lymphadenectomy \[LAD\]) stage III B/C/D, (American Joint Committee on Cancer \[AJCC\] 8th edition) of cutaneous origin or unknown primary. Patients must have at least one clinically evident lymph node metastasis (N1c patients are not eligible).
• This may be an initial presentation with primary tumor and nodal metastases or locoregional nodal relapse with history of resected primary melanoma
• Stage IIIB
• T0-3a N1b M0
• T1a-3a N2b M0
• Stage IIIC
• T0 or T3b-4b N2b M0
• T3b-4b N1b M0
• Any T N2c M0 (at least 1 clinically evident node)
• T0-4a N3b M0
• Stage IIID
• T4b N3b/c M0 (if 3c: at least 1 clinically evident node)
• Patient must have measurable disease on baseline imaging scans, obtained within 4 weeks prior to registration as defined by RECIST and by the following criteria
• The melanoma target tumor must be completely resectable as determined by a surgical oncologist or experienced melanoma surgeon
• Extensive satellitosis or in transit metastases are not considered completely resectable

You may not qualify if:

• Stage IV melanoma
• Patient must not have any prior treatment with BRAF inhibitor (BRAFi) or MEK inhibitor (MEKi)
• Patient must not have any evidence of distant metastases
• Patient must not have any prior adjuvant therapy at this disease presentation; prior immune therapy (such as adjuvant interferon or checkpoint inhibitors) is permitted if \>= 6 months from last treatment
• Patient must not have any prior radiation to the site of evaluable disease
• Patient must not have active infection requiring treatment with parenteral antibiotics
• Patient must not have active hepatitis B, and/or active hepatitis C infection given concerns for drug interactions or increased toxicities. Testing is not required
• Patient must not have other significant medical, surgical, or psychiatric conditions that in the opinion of the investigator may interfere with compliance, make the administration of study medications hazardous
• Patient must not have had previous or concurrent other malignancy with the following exceptions:
• Adequately treated basal cell or squamous cell carcinoma of the skin, in situ carcinoma of the cervix
• Other solid tumor: if treated and without evidence of recurrence for at least 2 years prior to study entry
• Women must not be pregnant or breast-feeding due to potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the systemic antineoplastic medications, as well as surgery and radiation being used. Patients must also not expect to conceive or father children from the time of registration, while on study, treatment, and until at least 30 days after the last dose of study treatment (for female patients) and 90 days after the last dose of study treatment (for male patients). All females of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy. A female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
• Patient must not have known hypersensitivity or contraindication to any component of binimetinib or encorafenib or their excipients
• Patient must not have impaired cardiovascular function or clinically significant cardiovascular disease including, but not limited to, any of the following:
• History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty or stenting) \< 6 months prior to registration

Sponsors & Collaborators

• ECOG-ACRIN Cancer Research Group: lead
• National Cancer Institute (NCI): collaborator

Study Sites (10)

Los Angeles County-USC Medical Center

Los Angeles, California, 90033, United States

Location

USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Siteman Cancer Center at Saint Peters Hospital

City of Saint Peters, Missouri, 63376, United States

Location

Siteman Cancer Center at West County Hospital

Creve Coeur, Missouri, 63141, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Siteman Cancer Center-South County

St Louis, Missouri, 63129, United States

Location

Siteman Cancer Center at Christian Hospital

St Louis, Missouri, 63136, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, 53792, United States

Location

MeSH Terms

Conditions

Lymphatic Metastasis; Melanoma

Interventions

binimetinib; encorafenib; alovudine

Condition Hierarchy (Ancestors)

Neoplasm Metastasis; Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Study Statistician
• Organization: ECOG-ACRIN Statistical Office

eatrials@jimmy.harvard.edu

617-632-3012

Study Officials

• Leslie A Fecher

  ECOG-ACRIN Cancer Research Group

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 6, 2020
• First Posted: January 9, 2020
• Study Start: September 22, 2021
• Primary Completion: June 10, 2024
• Study Completion: January 31, 2025
• Last Updated: April 1, 2026
• Results First Posted: June 8, 2025

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

US (10)