Binimetinib and Nivolumab for the Treatment of Locally Advanced Unresectable or Metastatic BRAF V600 Wildtype Melanoma

NCT04375527 | Terminated Phase 2 DMC FDA Drug

• 2 other identifiers: 19-002060NCI-2020-02590
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well binimetinib and nivolumab work in treating patients with BRAF V600 wildtype melanoma that has spread to nearby tissues or lymph nodes and cannot be removed by surgery (locally advanced unresectable) or has spread to other places in the body (metastatic). Binimetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving binimetinib and nivolumab together may work better in treating patients with melanoma compared to nivolumab alone.

Conditions

Clinical Stage III Cutaneous Melanoma AJCC V8; Clinical Stage IV Cutaneous Melanoma AJCC V8; Locally Advanced Cutaneous Melanoma; Metastatic Cutaneous Melanoma; Pathologic Stage III Cutaneous Melanoma AJCC V8; Pathologic Stage IIIA Cutaneous Melanoma AJCC V8; Pathologic Stage IIIB Cutaneous Melanoma AJCC V8; Pathologic Stage IIIC Cutaneous Melanoma AJCC V8; Pathologic Stage IIID Cutaneous Melanoma AJCC V8; Pathologic Stage IV Cutaneous Melanoma AJCC V8; Unresectable Cutaneous Melanoma

Outcome Measures

Primary Outcomes (1)

• Objective response rate

  Will be defined as the total number of patients with confirmed responses of either complete response or partial response divided by the total number of subjects in the enrolled population per Response Evaluation Criteria in Solid Tumors 1.1 by investigator assessment. Will be calculated along with the corresponding exact one-sided 95% Clopper-Pearson confidence interval.

  Up to 26 months

Secondary Outcomes (4)

• Progression-free survival

  From first dose of study drug to the date of progressive disease first documented disease progression or death due to any cause by investigator assessment, or the start of secondary antitumor therapy, whichever occurs first, assessed up to 26 months

• Clinical benefit rate

  Up to 26 months

• Overall survival

  From first dose of study drug and death due to any cause, assessed up to 26 months

• Duration of response

  From the time measurement criteria is met for complete response/partial response (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 26 months

Other Outcomes (1)

• Pharmacodynamic marker analysis

  Up to disease progression, assessed up to 26 months

Study Arms (1)

Treatment (binimetinib, nivolumab)

EXPERIMENTAL

Patients receive binimetinib PO BID on days 1-28 and nivolumab IV over 30 minutes on day 1. Treatment repeats every 4 weeks for up to 12 cycles in the absence of disease progression or unacceptable toxicity.

Drug: Binimetinib; Biological: Nivolumab; Other: Questionnaire Administration

Interventions

Binimetinib DRUG

Given PO

Also known as: ARRY-162, ARRY-438162, MEK162, Mektovi

Treatment (binimetinib, nivolumab)

Nivolumab BIOLOGICAL

Given IV

Also known as: BMS-936558, MDX-1106, NIVO, ONO-4538, Opdivo

Treatment (binimetinib, nivolumab)

Questionnaire Administration OTHER

Ancillary studies

Treatment (binimetinib, nivolumab)

Eligibility Criteria

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

You may qualify if:

• Males or females age \>= 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1
• Histologically confirmed locally advanced/unresectable or metastatic cutaneous melanoma
• Measurable disease per RECIST version (v.) 1.1 criteria using imaging scans, OR peripheral lesions that can be adequately documented with a picture and a ruler even if they do not meet RECIST criteria
• Patient must have failed prior alphaPD-1 or alphaPD-1 + alphaCTLA-4 therapy in the metastatic setting
• V600BRAF wildtype tumor status confirmed by Clinical Laboratory Improvement Act (CLIA) approved lab
• Hemoglobin \>= 8.0 g/dL
• Whole blood cell count (WBC) \>= 2,000/mm\^3
• Absolute neutrophil count \>= 1,500/mm\^3
• Platelet count \>= 75,000/mm\^3
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 3.0 x institutional upper limit of normal (ULN), (=\< 5.0 x ULN in those with hepatic metastases)
• Bilirubin =\< 1.5 x ULN; for subjects with documented/suspected Gilbert's disease, bilirubin =\< 3 x ULN
• Albumin \>= 2.5 g/dl
• Serum creatinine =\< 2.0 x upper limit of normal (ULN)
• Left ventricular ejection fraction (LVEF) \>= 50% assessed by echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scan completed =\< 180 days (6 months) before initiation of protocol treatment

You may not qualify if:

• Contraindications to tumor biopsy (coagulopathy, known history of keloid formation, etc.)
• Women who are pregnant or breastfeeding
• Prior therapy with a MEK inhibitor (e.g., binimetinib, trametinib, cobimetinib)
• Known hypersensitivity or contraindication to any component of binimetinib or its excipients
• Inability to swallow and retain study drug
• Patients who have received prior lines of systemic therapy in the advanced/metastatic setting (not including, neoadjuvant, adjuvant, or maintenance therapy)
• Received anticancer therapy including chemotherapy, immunotherapy, or antineoplastic biologic therapy (e.g., erlotinib, cetuximab, bevacizumab etc.), within 14 days prior to start of study treatment or exposure to any investigational drug within 7 days prior to screening visit or for which 5 half-lives have not elapsed
• Participants who have undergone major surgery (e.g., in-patient procedures) =\< 6 weeks prior to start of study treatment or who have not recovered from side effects of such procedure
• Participants who have had radiotherapy =\< 14 days prior to start of study treatment or who have not recovered from side effects of such procedure. Note: Palliative radiation therapy must be complete 7 days prior to the first dose of study treatment
• Participants who have not recovered to =\< grade 1 from toxic effects of prior therapy before starting study treatment
• Note: Stable chronic conditions (=\< grade 2) that are not expected to resolve (such as neuropathy, myalgia, alopecia, prior therapy-related endocrinopathies) are exceptions and may enroll
• Uncontrolled or symptomatic brain metastases or leptomeningeal carcinomatosis that are not stable, require steroids, are potentially life-threatening or have required radiation within 28 days prior to starting study drug. Note: Patients with previously treated brain metastases may participate provided they are stable (e.g., without evidence of progression by radiographic imaging for at least 28 days before the first dose of study treatment and neurologic symptoms have returned to baseline), and have no evidence of new or enlarging brain metastases or central nervous system (CNS) edema, and does not require steroids at least 7 days before the first dose of study treatment
• Subjects with active, known, or suspected autoimmune disease. Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll
• Uncontrolled or significant cardiovascular disease including, but not limited to, any of the following:
• Myocardial infarction (MI) or stroke/transient ischemic attack (TIA) within the 6 months prior to consent

Sponsors & Collaborators

• Jonsson Comprehensive Cancer Center: lead
• Array BioPharma: collaborator
• Bristol-Myers Squibb: collaborator

Study Sites (1)

University of California at Los Angeles

Los Angeles, California, 90095, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

binimetinib; Nivolumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Roger Lo, MD

  UCLA / Jonsson Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: May 1, 2020
• First Posted: May 5, 2020
• Study Start: December 3, 2020
• Primary Completion: November 22, 2024
• Study Completion: November 22, 2024
• Last Updated: December 4, 2024

Record last verified: 2024-11

Locations

US (1)