What side effects are associated with this type of intervention?

Common side effects of treatments for thyroid cancer, particularly those involving enzyme inhibitors like Encorafenib and Binimetinib, include gastrointestinal issues, increased liver enzymes, hypertension, and skin reactions. When combined with immune checkpoint inhibitors like Nivolumab, additional immune-related adverse events may occur, such as inflammation of the lungs (pneumonitis), liver (hepatitis), intestines (colitis), and endocrine organs (thyroiditis, adrenal insufficiency). These side effects result from the immune system attacking normal tissues along with cancer cells.

What prior FDA approvals exist?

The FDA has approved several treatments for thyroid cancer that involve enzyme inhibition and immune system activation. For instance, kinase inhibitors like Sorafenib and Lenvatinib have been approved for radioiodine-refractory differentiated thyroid cancer due to their ability to inhibit multiple kinases involved in tumor growth. Additionally, Pembrolizumab, an immune checkpoint inhibitor similar to Nivolumab, has been approved for tumors with specific genetic features, including some thyroid cancers. These treatments align with the mechanisms of action being studied in the trial involving Encorafenib, Binimetinib, and Nivolumab.

What other types of research exist?

Promising novel alternatives for thyroid cancer treatment in 2024 include: 1) PD-1/PD-L1 inhibitors such as Pembrolizumab and Avelumab, which have shown efficacy in various cancers including thyroid cancer. 2) Combination therapies involving other targeted agents like Lenvatinib or Sorafenib, which are kinase inhibitors used in thyroid cancer. 3) Emerging therapies like nonagonistic CD28 antibodies, which are in preclinical development and may offer new mechanisms of action. Patients should discuss these options with their oncologist to determine the best course of action based on their specific condition.

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Kinase Inhibitor

Encorafenib + Binimetinib +/- Nivolumab for Thyroid Cancer

Phase 2

Recruiting

Led By Matthew H Taylor

Research Sponsored by Providence Health & Services

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Eastern Cooperative Oncology Group (ECOG) performance status =< 1

Histologically (or cytologically) confirmed diagnosis of metastatic, radioiodine (RAI) refractory, BRAFV600E/M mutant differentiated thyroid cancer (DTC)

Must not have

Impaired cardiovascular function or clinically significant cardiovascular diseases

History of allergy or hypersensitivity to any monoclonal antibody

Timeline

Screening 3 weeks

Treatment Varies

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

Awards & highlights

No Placebo-Only Group

Summary

This trial studies how well encorafenib and binimetinib, with or without nivolumab, work in treating a specific type of thyroid cancer that has spread and doesn't respond to usual treatments. The drugs aim to stop cancer growth and help the immune system fight the cancer. Encorafenib and binimetinib are used in combination to treat BRAF V600 mutation-positive melanoma, showing improved response rates and survival.

Who is the study for?

This trial is for adults with metastatic, radioiodine-refractory thyroid cancer that has a BRAF V600 mutation. Participants must have measurable disease, be in good physical condition (ECOG status <=1), and not be pregnant or nursing. They should not have had certain prior treatments or conditions that could affect the study's safety.

What is being tested?

The effectiveness of encorafenib and binimetinib, with or without nivolumab, is being tested on patients with specific thyroid cancer. The goal is to see if these drugs can stop tumor growth by blocking enzymes needed for cell growth and boosting the immune system's ability to fight cancer.

What are the potential side effects?

Potential side effects include fatigue, skin reactions, heart issues like changes in heartbeat rhythm, liver problems such as hepatitis, muscle pain or weakness due to elevated creatine kinase levels, allergic reactions to monoclonal antibodies like nivolumab.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am fully active and can carry on all pre-disease activities without restriction.

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My thyroid cancer is advanced, does not respond to radioiodine, and has a specific BRAF mutation.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have heart problems or significant heart disease.

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I am allergic to some monoclonal antibody medications.

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I have a digestive condition that affects how I absorb medication.

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I have a history of pancreatitis.

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I have a muscle disorder that might increase my CK levels.

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I am on steroids or other drugs that affect my immune system.

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I have previously been treated with immunotherapy.

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I have been treated with specific drugs for cancer mutation.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

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

Screening ~ 3 weeks

Treatment ~ Varies

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

This trial's timeline: 3 weeks for screening, Varies for treatment, and from date of randomization until the date of death from any cause, assessed for up to 1 year for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Overall response rate (ORR)

Secondary study objectives

Duration of response (DOR)

Incidence of grade >= 3 toxicities

Overall survival

+1 more

Side effects data

From 2022 Phase 3 trial • 702 Patients • NCT02928224

78%

Diarrhoea

68%

Dermatitis acneiform

59%

Nausea

54%

Fatigue

51%

Vomiting

51%

Dry Skin

43%

Pyrexia

43%

Anaemia

41%

Decreased appetite

38%

Abdominal pain

38%

Constipation

35%

Dyspnoea

32%

Vision blurred

30%

Blood creatine increased

30%

Blood creatine phosphokinase increased

24%

Arthralgia

24%

Myalgia

24%

Skin fissures

22%

Back Pain

22%

Dizziness

19%

Malaise

19%

Urinary tract infection

19%

Headache

19%

Aspartate aminotransferase increased

16%

Asthenia

16%

Stomatitis

16%

Oedema peripheral

16%

PPE syndrome

16%

Hypomagnesaemia

16%

Rash maculo-papular

16%

Palmar-planar erythrodysaesthesia

16%

Chills

16%

Paronychia

16%

Rash pustular

16%

Alanine aminotransferase increased

16%

Dysgeusia

16%

Peripheral sensory neuropathy

14%

Cough

14%

Abdominal pain upper

14%

Infusion-related reaction

14%

Ejection fraction decreased

14%

Dry eye

11%

Trichiasis

11%

Pollakiuria

11%

Vitreous floaters

11%

Dyspepsia

11%

Hypoalbuminaemia

11%

Hypertension

11%

Tumour Pain

Rhinitis allergic

Hypokalaemia

Visual impairment

Infusion related reaction

Macular oedema

Hypertrichosis

Iron deficiency

Nasopharyngitis

Weight decreased

Flank pain

Proteinuria

Rash

Pruritus

Pain in extremity

Blood bilirubin increased

Rhinnorrhoea

Hypotension

Pleural effusion

Restless legs syndrome

Nervous system disorder

Wound

Trichomegaly

Infection

Hypocalcaemia

Hypophosphataemia

Rectal haemorrhage

Musculoskeletal pain

Anal haemorrhage

Ascites

Colitis

Abdominal pain lower

Nail disorder

Pruritus generalised

Bone pain

Musculoskeletal chest pain

Chorioretinopathy

Urinary incontinence

Insomnia

Gastroesophageal reflux disease

Abdominal distension

Eczema

Cystitis

Renal failure

Conjunctivitis

Syncope

Dehydration

Dry Mouth

Skin hyperpigmentation

Muscle spasms

Erythema

Retinal detachment

Pulmonary embolism

Dysphonia

Haematuria

Blood creatinine increased

Depression

Palpitations

Tumour pain

Melanocytic naevus

Large intestinal ulcer

Kidney infection

Large intestinal ulcer hemorrhage

Urinary tract infection bacterial

Epistaxis

Hyperkeratosis

Rectal hemorrhage

Streptococcal infection

Alopecia

Upper respiratory tract infection

Skin papilloma

Large intestine perforation

Bacterial sepsis

Cholangitis

Urinary tract obstruction

Confusional state

Device occlusion

Back pain

Rhabdomyolysis

Colon cancer

Sepsis

Acute kidney injury

Large intestine ulcer

Neutropenia

Bacteria sepsis

Hydronephrosis

Neuropathy peripheral

Abdominal abscess

Hyperglycaemia

100%

80%

60%

40%

20%

Study treatment Arm

Combined Safety Lead-in

Phase 3: Triplet Arm

Phase 3: Doublet Arm

Phase 3: Control Arm

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: Arm II (encorafenib, binimetinib, nivolumab) - CLOSEDExperimental Treatment3 Interventions

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.

Group II: Arm I (encorafenib, binimetinib)Experimental Treatment2 Interventions

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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Encorafenib

2022

Completed Phase 3

~970

Binimetinib

2018

Completed Phase 3

~1250

Nivolumab

2014

Completed Phase 3

~5220

0 / 10Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for thyroid cancer, such as encorafenib and binimetinib, work by inhibiting specific enzymes that are essential for cancer cell growth and proliferation. Encorafenib targets the BRAF V600 mutation, while binimetinib inhibits MEK enzymes, both of which are part of the MAPK/ERK signaling pathway. Nivolumab, on the other hand, is an immunotherapy that enhances the body's immune response against cancer cells by blocking the PD-1 protein on immune cells, thereby preventing cancer cells from evading immune detection. These treatments are particularly important for thyroid cancer patients with metastatic and radioiodine-refractory disease, as they provide new avenues for controlling tumor growth and improving patient outcomes.

Nivolumab-induced hypothyoidism with consequent hypothyroid related myopathy.