What side effects are associated with this type of intervention?

The most common treatments for thyroid cancer involving immune checkpoint inhibitors like Nivolumab (PD-1 inhibitor) and Ipilimumab (CTLA-4 inhibitor) are associated with several immune-related adverse events. Common side effects include fatigue, rash, diarrhea, and pruritus. More severe but less frequent side effects can include pneumonitis, colitis, hepatitis, various endocrinopathies (such as thyroiditis, hypophysitis, and adrenal insufficiency), and nephritis. These side effects require careful monitoring and management during treatment.

What prior FDA approvals exist?

The FDA has approved several treatments for thyroid cancer, including targeted therapies and immunotherapies. While specific approvals for Nivolumab and Ipilimumab in thyroid cancer are not detailed, these drugs are being studied for their potential benefits. Nivolumab is a PD-1 inhibitor, and Ipilimumab is a CTLA-4 inhibitor, both of which are types of immune checkpoint inhibitors. These drugs work by enhancing the body's immune response against cancer cells. Other FDA-approved treatments for thyroid cancer include targeted therapies like dabrafenib and trametinib for BRAF-mutated anaplastic thyroid carcinoma.

What other types of research exist?

Currently, the provided context does not mention specific novel alternatives to Nivolumab and Ipilimumab for thyroid cancer. However, other PD-1 inhibitors like Pembrolizumab and PD-L1 inhibitors such as Avelumab, which have shown efficacy in other cancers, could be considered. Additionally, ongoing research into combination therapies involving checkpoint inhibitors and other agents may offer new options in the near future.

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Checkpoint Inhibitor

Nivolumab + Ipilimumab for Thyroid Cancer

Phase 2

Waitlist Available

Led By Jochen Lorch, MD

Research Sponsored by Dana-Farber Cancer Institute

Eligibility Criteria Checklist

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

Must have

ECOG performance status ≤2 (Karnofsky ≥60%)

Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year

Must not have

Uncontrolled intercurrent illness including ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

Patients with active brain metastases

Timeline

Screening 3 weeks

Treatment Varies

Follow Up median (range) follow-up (months) for dtc cohort was 24.0 (1.84 - 24.7), for mtc cohort was 24.0 (23.0-24.2), and for atc cohort was 22.2 (0.46 - 26.1).

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing two drugs, nivolumab and ipilimumab, to see if they can help treat thyroid cancer by boosting the immune system to fight cancer cells. These drugs have shown promising results in treating various cancers by enhancing the immune system's response to tumors.

Who is the study for?

This trial is for adults with thyroid cancer, including those who've had prior treatments. It's open to patients with medullary thyroid cancer after TKI failure and anaplastic thyroid cancer, as well as metastatic RAI refractory differentiated thyroid cancer. Participants must be in good health otherwise, able to consent, and use effective contraception if of childbearing potential.

What is being tested?

The study tests a combination of two investigational drugs: Nivolumab (Opdivo™) and Ipilimumab (Yervoy™), for treating different types of advanced or aggressive thyroid cancers that have not responded well to previous treatments.

What are the potential side effects?

Potential side effects include immune-related reactions such as inflammation in various organs, skin rash, hormone gland problems (like the thyroid), digestive issues like diarrhea or colitis, liver inflammation, fatigue and can affect how other organs function.

Eligibility Criteria

Inclusion Criteria

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

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I can care for myself but may not be able to do active work.

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I use a highly effective birth control method.

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I am 18 years old or older.

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I can take care of myself but might not be able to do active work.

Exclusion Criteria

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

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I do not have any severe illnesses or social situations that would stop me from following the study's requirements.

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I have active cancer spread to my brain.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ median (range) follow-up (months) for dtc cohort was 24.0 (1.84 - 24.7), for mtc cohort was 24.0 (23.0-24.2), and for atc cohort was 22.2 (0.46 - 26.1).

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~median (range) follow-up (months) for dtc cohort was 24.0 (1.84 - 24.7), for mtc cohort was 24.0 (23.0-24.2), and for atc cohort was 22.2 (0.46 - 26.1).

This trial's timeline: 3 weeks for screening, Varies for treatment, and median (range) follow-up (months) for dtc cohort was 24.0 (1.84 - 24.7), for mtc cohort was 24.0 (23.0-24.2), and for atc cohort was 22.2 (0.46 - 26.1). for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Best Overall Response Rate

Secondary study objectives

Median Progression Free Survival

Overall Survival at 2 Years (OS2)

Treatment-Related Adverse Events Rate

Side effects data

From 2024 Phase 3 trial • 529 Patients • NCT02017717

80%

Fatigue

70%

Diarrhoea

70%

Headache

40%

Vomiting

40%

Aspartate aminotransferase increased

40%

Rash maculo-papular

40%

Alanine aminotransferase increased

40%

Lipase increased

30%

Partial seizures

30%

Hemiparesis

30%

Gait disturbance

30%

Fall

30%

Cough

30%

Dry skin

30%

Amylase increased

30%

Nausea

30%

Confusional state

20%

Malignant neoplasm progression

20%

Pyrexia

20%

Candida infection

20%

Mucosal infection

20%

Decreased appetite

20%

Back pain

20%

Dysphonia

20%

Hypotension

20%

Colitis

20%

Hyperthyroidism

20%

Oedema peripheral

20%

Muscular weakness

20%

Hypothyroidism

10%

Tinnitus

10%

Cushingoid

10%

Diabetic ketoacidosis

10%

Procedural haemorrhage

10%

Blood bilirubin increased

10%

Bradycardia

10%

Sinus tachycardia

10%

Hyperglycaemia

10%

Hypocalcaemia

10%

Neck pain

10%

Brain oedema

10%

Hydrocephalus

10%

Lethargy

10%

Seizure

10%

Hypertension

10%

Palpitations

10%

Cheilitis

10%

Presyncope

10%

Face oedema

10%

Oedema

10%

Conjunctivitis

10%

Enterocolitis infectious

10%

Oral candidiasis

10%

Pneumonia

10%

Sinusitis

10%

Staphylococcal infection

10%

Blood alkaline phosphatase increased

10%

Spinal pain

10%

Tremor

10%

Dizziness

10%

Dysarthria

10%

Urinary retention

10%

Dyspnoea exertional

10%

Nasal congestion

10%

Pneumonitis

10%

Dermatitis

10%

Erythema

10%

Rash

10%

Klebsiella infection

10%

Hypomagnesaemia

10%

Syncope

10%

Haemorrhage intracranial

10%

Pancreatitis

10%

Cholecystitis

10%

Upper respiratory tract infection

10%

Acute kidney injury

10%

Dermatitis bullous

10%

Lymphopenia

10%

Optic nerve disorder

10%

Visual impairment

10%

Dehydration

10%

Hypokalaemia

10%

Scoliosis

10%

Cognitive disorder

10%

Memory impairment

10%

Hallucination

10%

Insomnia

10%

Irritability

10%

Urinary incontinence

10%

Dyspnoea

10%

Dermatitis acneiform

10%

Pelvic venous thrombosis

10%

Sepsis

100%

80%

60%

40%

20%

Study treatment Arm

Cohort 1: Arm N1+I3

Cohort 2: Arm B

Part A Cohort 1c: Arm N3+RT+TMZ

Part A Cohort 1d: Arm N3+RT

Part B Cohort 1c: Arm N3+RT+TMZ

Part B Cohort 1d: Arm N3+RT

Cohort 1: Arm N3

Cohort 1b: Arm N3+I1

Cohort 2: Arm N3

Awards & Highlights

No Placebo-Only Group

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

Trial Design

10Treatment groups

Experimental Treatment

Group I: Medullary Thyroid Cancer (Exploratory Cohort)Experimental Treatment2 Interventions

Medullary Thyroid Cancer (MTC) participants received Ipilimumab (Ipi) 1mg/kg q6 weeks and Nivolumab (Nivo) 3mg/kg q6 weeks sequentially either Ipi or Nivo first with 2 weeks apart prior to start of either Ipi or Nivo second, or started Ipi or Nivo together. Per protocol order in sequential design was not expected to impact efficacy rather was for exploratory correlative analyses. Participants were treated indefinitely until disease progression or withdrawal for other reasons.

Group II: MTC - Nivolumab alone for two weekExperimental Treatment2 Interventions

Medullary Thyroid Cancer (MTC)participants received Ipilimumab 1mg/kg q6 weeks via IV infusion, starting two weeks after Nivolumab 3mg/kg q6 weeks.

Group III: MTC - Ipilimumab alone for two weeksExperimental Treatment2 Interventions

Medullary Thyroid Cancer (MTC) participants received Nivolumab 3mg/kg q6 weeks via IV infusion, starting two weeks after Ipilimumab 1mg/kg q6 weeks.

Group IV: Differentiated Thyroid Cancer (Primary cohort)Experimental Treatment2 Interventions

Differentiated Thyroid Cancer (DTC) participants received Ipilimumab (Ipi) 1mg/kg q6 weeks and Nivolumab (Nivo) 3mg/kg q6 weeks sequentially either Ipi or Nivo first with 2 weeks apart prior to start of either Ipi or Nivo second. Per protocol order in sequential design was not expected to impact efficacy rather was for exploratory correlative analyses. Participants were treated indefinitely until disease progression or withdrawal for other reasons.

Group V: DTC - Nivolumab alone for two weeksExperimental Treatment2 Interventions

Differentiated Thyroid Cancer (DTC) participants received Ipilimumab 1mg/kg q6 weeks via IV infusion, starting two weeks after Nivolumab 3mg/kg q6 weeks.

Group VI: DTC - Ipilimumab alone for two weeksExperimental Treatment2 Interventions

Differentiated Thyroid Cancer (DTC) participants received Nivolumab 3mg/kg q6 weeks via IV infusion, starting two weeks after Ipilimumab 1mg/kg q6 weeks.

Group VII: Anaplastic Thyroid Cancer (Exploratory Cohort)Experimental Treatment2 Interventions

Anaplastic Thyroid Cancer (ATC) participants received Ipilimumab (Ipi) 1mg/kg q6 weeks and Nivolumab (Nivo) 3mg/kg q6 weeks sequentially either Ipi or Nivo first with 2 weeks apart prior to start of either Ipi or Nivo second prior to study amendment or in combination from the start after study amendment due to aggressive nature of the disease in this cohort. Per protocol order in sequential design was not expected to impact efficacy rather was for exploratory correlative analyses. Participants were treated indefinitely until disease progression or withdrawal for other reasons.

Group VIII: ATC - Nivolumab alone for two weekExperimental Treatment2 Interventions

Anaplastic Thyroid Cancer (ATC) received Ipilimumab 1mg/kg q6 weeks via IV infusion, starting two weeks after Nivolumab 3mg/kg q6 weeks.

Group IX: ATC - Ipilimumab alone for two weekExperimental Treatment2 Interventions

Anaplastic Thyroid Cancer (ATC) received Nivolumab 3mg/kg q6 weeks via IV infusion, starting two weeks after Ipilimumab 1mg/kg q6 weeks.

Group X: ATC - Ipilimumab + NivolumabExperimental Treatment2 Interventions

Anaplastic Thyroid Cancer (ATC) received Nivolumab 3mg/kg q6 weeks and Ipilimumab 1mg/kg q6 weeks via IV infusion.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Ipilimumab

2015

Completed Phase 3

~3070

Nivolumab

2015

Completed Phase 3

~4010

0 / 6Eligibility 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

Nivolumab is a PD-1 inhibitor that works by blocking the programmed cell death protein 1 (PD-1) pathway, which cancer cells exploit to evade immune detection. By inhibiting this pathway, Nivolumab enhances the body's immune response against cancer cells. Ipilimumab, on the other hand, is a CTLA-4 inhibitor that blocks the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) pathway, which also downregulates immune responses. By inhibiting CTLA-4, Ipilimumab promotes a stronger immune attack on cancer cells. For thyroid cancer patients, these mechanisms are crucial as they can potentially lead to more effective targeting and destruction of cancer cells by the immune system, offering a promising therapeutic approach for those with advanced or refractory disease.