Encorafenib and Binimetinib With or Without Nivolumab in Treating Patients With Metastatic Radioiodine Refractory BRAF V600 Mutant Thyroid Cancer

NCT04061980 | Active Not Recruiting Phase 2 FDA Drug

• 3 other identifiers: 2020000039IST-818-210XCA209-73R
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well encorafenib and binimetinib given with or without nivolumab works in treating patients with BRAF V600 mutation positive thyroid cancer that has spread to other places in the body (metastatic) and does not respond to radioiodine treatment (refractory). Encorafenib and 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. The trial aims to find out if the combination of encorafenib and binimetinib, with and without study nivolumab, is a safe and effective way to treat metastatic radioiodine refractory thyroid cancer.

Conditions

BRAF NP_004324.2:p.V600M; BRAF V600E Mutation Present; Metastatic Thyroid Gland Carcinoma; Refractory Thyroid Gland Carcinoma; Stage IV Differentiated Thyroid Gland Carcinoma AJCC v8; Stage IVB Differentiated Thyroid Gland Carcinoma AJCC v8; Stage IVA Differentiated Thyroid Gland Carcinoma AJCC v8

Keywords

Encorafenib; Binimetinib; Nivolumab; BRAF V600; Thyroid cancer; Radiodine refractory Thyroid Cancer; Phase 2; IST-818-210X; CA209-73R

Outcome Measures

Primary Outcomes (1)

• Overall response rate (ORR)

  ORR is defined as the proportion of participants with best overall response of complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 criteria. ORR at 6 months will be assessed using the efficacy evaluable analysis set. A point and 90% exact binomial confidence interval will be provided for each arm.

  From the start of randomization up to 6 months from first dose of study drugs

Secondary Outcomes (4)

• Progression free survival (PFS)

  From date of randomization until either tumor progression (per RECIST v1.1) or death, assessed for up to 12 months

• Overall survival

  From date of randomization until the date of death from any cause, assessed for up to 1 year

• Duration of response (DOR)

  From date of first documented CR or PR up to first documented progression or death due to any cause, assessed for up to 1 year

• Incidence of grade >= 3 toxicities

  From the first dose of assigned study intervention until 90 days from the last dose of assigned study intervention

Study Arms (2)

Arm I (encorafenib, binimetinib)

EXPERIMENTAL

Patients receive encorafenib PO QD and binimetinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Binimetinib; Drug: Encorafenib

Arm II (encorafenib, binimetinib, nivolumab) - CLOSED

EXPERIMENTAL

Patients receive encorafenib PO QD and binimetinib PO BID as in arm I. Patients also receive nivolumab IV over 30 minutes on day 1. Cycles with nivolumab repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

Drug: Binimetinib; Drug: Encorafenib; Biological: Nivolumab

Interventions

Binimetinib DRUG

Given PO

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

Arm I (encorafenib, binimetinib); Arm II (encorafenib, binimetinib, nivolumab) - CLOSED

Encorafenib DRUG

Given PO

Also known as: Braftovi, LGX 818, LGX-818, LGX818

Arm I (encorafenib, binimetinib); Arm II (encorafenib, binimetinib, nivolumab) - CLOSED

Nivolumab BIOLOGICAL

Given IV

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

Arm II (encorafenib, binimetinib, nivolumab) - CLOSED

Eligibility Criteria

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

You may qualify if:

• Ability to understand and the willingness to sign a written informed consent document
• Histologically (or cytologically) confirmed diagnosis of metastatic, radioiodine (RAI) refractory, BRAFV600E/M mutant differentiated thyroid cancer (DTC)
• Note: RAI refractoriness is defined as:
• The absence of uptake of RAI on either a low-dose diagnostic whole body scan, or a post-treatment RAI scan in measurable lesions
• Radiographic progression of disease within 12 months of the last course of RAI treatment, or
• Having a cumulative lifetime administered dose of \> 600 mCi of RAI
• Measurable disease meeting the following criteria and confirmed by radiography review:
• At least 1 lesion of \>= 1.0 cm in the longest diameter for a non-lymph node or \> 1.5 cm in the short-axis diameter for a lymph node metastasis that is serially measurable according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 using computed tomography/magnetic resonance imaging (CT/MRI). If there is only 1 target lesion and it is a non-lymph node, it should have a longest diameter of \>= 1.5 cm
• Lesions that have had external beam radiotherapy or locoregional therapies such as radiofrequency (RF) ablation must show evidence of progressive disease based on RECIST 1.1 to be deemed a target lesion.
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 1
• Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L
• Hemoglobin (Hgb) \>= 9 g/dL
• Platelets (PLT) \>= 75 x 10\^9/L
• Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) =\< 2.5 x upper limit of normal (ULN); participants with liver metastases =\< 5 x ULN
• Total bilirubin =\< 1.5 x ULN

You may not qualify if:

• Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational agent/device within 4 weeks of first dose of study intervention
• Note: Individuals in the follow-up phase of a prior investigational study may participate as long as it has been 4 weeks since last dose of the previous investigational agent of device
• Participants with active, known, or suspected autoimmune disease. Participants with type I diabetes mellitus, residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment are permitted to enroll
• Prior treatment with selective/potent BRAF/MEK inhibitors including vemurafenib, dabrafenib, encorafenib, selumetinib, trametinib, cobimetinib, binimetinib.
• Note: Prior therapy with oral multikinase inhibitors (e.g., lenvatinib, sorafenib, cabozantinib, pazopanib, sunitinib, etc.) remain eligible for study participation.
• Prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody (including ipilimumab or any other antibody or drug specifically targeting T cell co-stimulation or immune checkpoint pathways)
• Participants with a condition requiring systemic treatment with either corticosteroids (\>= 10 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids are permitted in the absence of active autoimmune disease
• History of allergy or hypersensitivity to any monoclonal antibody
• History or current evidence of retinal vein occlusion (RVO) or current risk factors to RVO (e.g. uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes); history of retinal degenerative disease
• Previous or concurrent malignancy within 3 years of study entry, with the following exceptions:
• Adequately treated basal or squamous cell skin cancer, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in-situ of the cervix, or other noninvasive or indolent malignancy; OR
• Other solid tumors treated curatively in which the expected rate of recurrence within 5 years is \< 5%
• Impaired cardiovascular function or clinically significant cardiovascular diseases, including 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 screening
• Symptomatic congestive heart failure (i.e. grade 2 or higher), history or current evidence of clinically significant cardiac arrhythmia and/or conduction abnormality \< 6 months prior to screening. Exceptions include asymptomatic/well-controlled atrial fibrillation/flutter or paroxysmal supraventricular tachycardia

Sponsors & Collaborators

• Providence Health & Services: lead
• Providence Cancer Center, Earle A. Chiles Research Institute: collaborator

Study Sites (1)

Providence Portland Medical Center

Portland, Oregon, 97213, United States

Location

MeSH Terms

Conditions

Thyroid Neoplasms

Interventions

binimetinib; encorafenib; Nivolumab

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Endocrine System Diseases; Thyroid 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

• Matthew H Taylor

  Providence Health & Services

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: August 18, 2019
• First Posted: August 20, 2019
• Study Start: October 30, 2020
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): December 30, 2028
• Last Updated: April 13, 2026

Record last verified: 2026-04

Locations

US (1)