Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Melanoma

Melanoma, Cutaneous Malignant

Skin Neoplasms

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Nivolumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

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.

Binimetinib

Questionnaire Administration

Roger Lo, MD

Roger Lo

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.

PRIMARY OBJECTIVE:

I. Objective response rate (ORR), which is defined as the proportion of response-evaluable participants either with a confirmed complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, as determined by the investigator assessment, at best overall response.

SECONDARY OBJECTIVE:

I. Progression-free survival (PFS), clinical benefit rate (CR + PR + stable disease \[SD\] among response-evaluable participants, per RECIST 1.1), overall survival (OS) and duration of response (DOR).

EXPLORATORY OBJECTIVE:

I. Evaluation of histologic evidence of response (p-ERK reduction in residual tumor cells and CD8 T cell or tumor infiltrating lymphocytes or tumor infiltrating lymphocyte \[TIL\] infiltration induced by combination treatment) using pretreatment and early on-treatment tumor biopsies.

OUTLINE:

Patients receive binimetinib orally (PO) twice daily (BID) on days 1-28 and nivolumab intravenously (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.

After completion of study treatment, patients are followed up every 3 months for up to 1 year, then annually thereafter.

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

A Phase 2 Study of Combination Treatment of Binimetinib and Nivolumab for Advanced V600BRAF Wildtype Melanoma With Innate Anti-PD-1 Resistance

Will use purely descriptive analysis to assess biomarkers (PDL1 status at baseline, baseline mutational load, presence of tumor infiltrating lymphocytes, hormone receptor status, T-cell receptor repertoire in tumor infiltrating lymphocytes and peripheral blood mononuclear cells). They will be further related to individual subject tumor responses.

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.

Will be assessed per Response Evaluation Criteria in Solid Tumors 1.1. Will be summarized using the Kaplan Meier method. Will be summarized descriptively (mean, standard deviation, median, first and third quartiles, minimum, maximum). Figures showing the Kaplan-Meier estimates will also be presented.

Will be defined as the proportion of response-evaluable participants who have achieved a confirmed complete response, partial response, and stable disease per Response Evaluation Criteria in Solid Tumors 1.1, as determined by the investigator assessment. Clinical benefit rate and the individual rates for complete response/partial response/stable disease will be summarized with the frequency count and the percentage of subjects in each category along with a 2-sided 95% exact confidence interval.

Will be summarized using the Kaplan Meier method. The Kaplan Meier estimates for the 1 year OS rates and the 2-sided 95% confidence interval of the rates using the Greenwood's formula will be reported. Will be summarized descriptively (mean, standard deviation, median, first and third quartiles, minimum, maximum). Figures showing the Kaplan-Meier estimates will also be presented.

Will be summarized using the Kaplan Meier method. Will be summarized descriptively (mean, standard deviation, median, first and third quartiles, minimum, maximum). Figures showing the Kaplan-Meier estimates will also be presented.

Spots Global Cancer Trial Database for locally advanced cutaneous melanoma