What is the mechanism of action of this treatment?

The most common treatments for Chordoma, particularly those being studied like Nivolumab and Relatlimab, work by enhancing the body's immune response against cancer cells. Nivolumab blocks the PD-1 receptor, preventing tumor cells from evading the immune system. Relatlimab targets the LAG-3 protein, reducing inhibitory signals that dampen the immune response. This combination is crucial for Chordoma patients as it aims to boost the immune system's ability to recognize and attack tumor cells, potentially improving disease control.

What side effects are associated with this type of intervention?

Common side effects of treatments for Chordoma, particularly those involving immune checkpoint inhibitors like Nivolumab (PD-1 inhibitor) and Relatlimab (LAG-3 inhibitor), include immune-related adverse events. These can manifest as pneumonitis, colitis, hepatitis, endocrinopathies (such as hypothyroidism and adrenal insufficiency), and skin reactions like rash and pruritus. Severe but less common side effects may include myocarditis and nephritis.

What prior FDA approvals exist?

As of now, there are no specific FDA-approved treatments for Chordoma that involve immune checkpoint inhibitors like Nivolumab (PD-1 inhibitor) and Relatlimab (LAG-3 inhibitor). However, immune checkpoint inhibitors have been approved for various other cancers, such as melanoma and non-small cell lung cancer, where drugs like Nivolumab and Pembrolizumab (another PD-1 inhibitor) have shown efficacy. The ongoing trial studying Nivolumab and Relatlimab for Chordoma aims to explore the potential of these drugs in enhancing the immune response against this rare cancer.

What other types of research exist?

Promising novel alternatives for Chordoma patients in 2024 may include other PD-1/PD-L1 inhibitors such as Pembrolizumab or Atezolizumab, CTLA-4 inhibitors like Ipilimumab, and emerging therapies targeting new immune checkpoints such as TIM-3 or TIGIT. Combination therapies involving these agents or novel small molecules could also be considered.

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Checkpoint Inhibitor

Nivolumab + Relatlimab for Advanced Chordoma

Phase 2

Waitlist Available

Led By Arun Singh

Research Sponsored by Jonsson Comprehensive Cancer Center

Eligibility Criteria Checklist

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

Must have

Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1

Males and their female partner(s) of child-bearing potential must use 2 forms of effective contraception (condom or vasectomy for males) from the last menstrual period of the female partner during the study treatment and agree to continue use for 6 months after the final dose of study treatment

Must not have

Active or prior documented inflammatory bowel disease (e.g. Crohn?s disease, ulcerative colitis) or a history of primary immunodeficiency

Unresolved toxicities from prior anticancer therapy, defined as having not resolved to National Cancer Institute?s (NCI?s) Common Terminology Criteria for Adverse Events (CTCAE) (NCI CTCAE version [v]4.03) grade 0 or 1, or to levels dictated in the inclusion/exclusion criteria with the exception of alopecia. Subjects with irreversible toxicity that is not reasonably expected to be exacerbated by nivolumab may be included (eg, hearing loss) after consultation with the Bristol-Myers Squibb (BMS) medical monitor

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial studies how well nivolumab and relatlimab work in treating patients with advanced chordoma. These special proteins help the immune system recognize and attack cancer cells. The trial aims to see if this combination can stop the cancer from growing and spreading. Nivolumab plus relatlimab is a fixed-dose combination immunotherapy developed by Bristol Myers Squibb for treating multiple types of advanced cancers.

Who is the study for?

This trial is for adults with advanced chordoma, a type of bone cancer. Participants must have tumors that can be measured, not be pregnant or breastfeeding, and agree to use effective contraception. They should have good physical function (ECOG PS 0-1) and adequate organ function. Those with recent surgery, certain heart conditions, previous anti-LAG3 antibody treatment, active infections or other serious health issues cannot join.

What is being tested?

The study tests nivolumab and relatlimab—monoclonal antibodies designed to stop tumor growth in patients with chordoma that has spread. It's a phase II trial aiming to see how well these drugs work together against this rare cancer type.

What are the potential side effects?

Potential side effects include immune-related reactions such as inflammation in various organs, skin rash or endocrine disorders; infusion-related symptoms like fever or chills; fatigue; possible liver enzyme changes; and an increased risk of infection.

Eligibility Criteria

Inclusion Criteria

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

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I am fully active or can carry out light work.

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I am using two effective birth control methods during and for 6 months after the study.

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My cancer is confirmed to be chordoma.

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I have a recent tumor sample large enough for testing.

Exclusion Criteria

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

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I have or had inflammatory bowel disease or a primary immunodeficiency.

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My side effects from previous cancer treatments are mild or gone, except for hair loss.

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I am currently being treated for a serious infection.

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I haven't taken any cancer treatment drugs in the last 7 days.

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I haven't had palliative surgery or radiation, nor taken steroids, in the last 28 days.

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I have a history of tuberculosis.

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I do not have active hepatitis B or C, nor HIV.

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I have had an autoimmune disease in the last 3 years.

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I have had an organ transplant and take drugs to suppress my immune system.

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I do not have significant heart problems or recent serious heart issues.

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I am unable to understand or sign the consent form.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 2 years for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Objective response rate (ORR) defined as the number of subjects with a best objective response (BOR) of confirmed complete response (CR) or partial response (PR) divided by the number of subjects

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

1Treatment groups

Experimental Treatment

Group I: Treatment (nivolumab and relatlimab)Experimental Treatment2 Interventions

Participants receive nivolumab intravenously (IV) over 60 minutes and relatlimab via infusion over 60 minutes on day 1. Courses repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Relatlimab

2019

Completed Phase 2

~1150

Nivolumab

2015

Completed Phase 3

~4010

0 / 15Eligibility 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 Chordoma, particularly those being studied like Nivolumab and Relatlimab, work by enhancing the body's immune response against cancer cells. Nivolumab blocks the PD-1 receptor, preventing tumor cells from evading the immune system. Relatlimab targets the LAG-3 protein, reducing inhibitory signals that dampen the immune response. This combination is crucial for Chordoma patients as it aims to boost the immune system's ability to recognize and attack tumor cells, potentially improving disease control.

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