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Metastatic MelanomaPhase 2NCT03724968

Nivolumab Plus Relatlimab or Ipilimumab in Metastatic Melanoma Stratified by MHC-II Expression

A Phase 2 study testing Nivolumab, Relatlimab and Ipilimumab in people with Metastatic Melanoma and Advanced Melanoma, run by Elizabeth Davis at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This is an open-label, non-randomized two arm Phase 2 study of intravenous nivolumab plus intravenous ipilimumab or intravenous relatlimab in patients with metastatic melanoma stratified by MHC-II expression. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Nivolumab, Relatlimab and Ipilimumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
2 participants
Where
1 siteUnited States
Study dates
17 Jan 2019to 28 May 2020
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Signed and dated written informed consent.
  • ≥ 18 years of age at the time of informed consent.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Histologically confirmed locally advanced/unresectable or metastatic melanoma.
  • Patients who have received prior anti-CTLA-4 or anti-PD-1/PD-L1 for adjuvant treatment of melanoma are eligible if > 6 months have elapsed between the last dose of adjuvant treatment and starting this study - provided there is no history of life-threatening toxicity related to such prior treatment, or such toxicity is unlikely to re-occur with standard countermeasures (e.g. hormone replacement after endocrinopathy).
  • Patients who have received adjuvant therapy with interferon and/or a BRAF inhibitor and/or MEK inhibitor for adjuvant therapy are permitted to enroll.
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  • At least one measureable target lesion as defined by RECIST 1.1 which can be followed byCT or MRI.
  • If located in a previously irradiated area, a tumor lesion is considered a measurable/target lesion only if subsequent disease progression in the lesion has been documented at least 90 days following completion of radiotherapy.
  • Adequate organ and bone marrow function ≤ 14 days prior to first dose of protocol-indicated treatment:
  • White blood cell count (WBC) ≥ 2,000/mm3
  • Absolute neutrophil count (ANC) ≥ 1,500/mm3
  • Platelets ≥ 75,000/mm3
  • Hemoglobin ≥ 8.0 g/dL.
  • Serum creatinine ≤ 2.0x upper limit of normal (ULN), or calculated creatinine clearance (CrCl) > 40 mL/min per the Cockcroft-Gault formula (Appendix 1).
  • Total bilirubin ≤ 1.5x ULN (except patients with Gilbert Syndrome, who must have total bilirubin < 3.0 mg/dL).
  • AST (aspartate aminotransferase) and ALT (alanine aminotransferase) ≤ 3.0x ULN (≤ 5.0x ULN in those with hepatic metastases)
  • Acceptable troponin level ≤ 14 days prior to first dose of protocol-indicated treatment:
  • Troponin T (TnT) or I (TnI) ≤ 2× institutional ULN.
  • Subjects with TnT or TnI levels between >1 to 2× ULN will be permitted if repeat levels within 24 hours are ≤ 1x ULN.
  • If TnT or TnI levels are >1 to 2× ULN within 24 hours, the subject may undergo a cardiac evaluation and be considered for treatment based on the discretion of the PI.
  • When repeat levels within 24 hours are not available, a repeat test should be conducted as soon as possible.
  • If TnT or TnI repeat levels beyond 24 hours are < 2x ULN, the subject may undergo a cardiac evaluation and be considered for treatment, based on the discretion of the PI.
  • Arm A: Corrected QT interval (QTc) by Fridericia's method (QTcF) assessed by electrocardiogram (ECG) completed ≤ 28 days before initiation of protocol treatment
  • QTcF ≤ 480 msec
  • Tumor tissue from a biopsy or resection obtained since completion of the last systemic therapy must be available for analysis of MHC-II status and for biomarker analysis. If a sample is not available or if the quantity or quality of tissue is insufficient to provide adequate results, an additional biopsy may be performed for MHC-II analysis. Patients cannot be enrolled on the study unless MHC-II is known.
  • Women must not be breastfeeding
  • A woman of childbearing potential must have a negative serum pregnancy test within 14 days prior to receiving first dose of protocol-indicated treatment, and must agree to follow instructions for using acceptable contraception (Appendix 4) from the time of signing consent, and for 165 days (24 weeks) after her last dose of protocol-indicated treatment.
  • A man able to father children who is sexually active with a woman of childbearing potential must agree to follow instructions for using acceptable contraception from the time of signing consent, and for 225 days (33 weeks) after his last dose of protocol-indicated treatment.

Who cannot join

  • Patients with uveal melanoma.
  • Prior systemic anticancer therapy for unresectable or metastatic melanoma.
  • Prior treatment with LAG-3 targeted agents.
  • Subjects with active, known, or suspected autoimmune disease. Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
  • Uncontrolled or significant cardiovascular disease including, but not limited to, any of the following:
  • Myocardial infarction (MI) or stroke/transient ischemic attack (TIA) within the 6 months prior to consent.
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  • Uncontrolled angina within the 3 months prior to consent.
  • Any history of clinically significant arrhythmias (such as ventricular tachycardia, ventricular fibrillation, torsades de pointes, or poorly controlled atrial fibrillation).
  • QTc prolongation > 480 msec.
  • History of other clinically significant cardiovascular disease (i.e., cardiomyopathy, congestive heart failure with New York Heart Association [NYHA] functional classification III-IV, pericarditis, significant pericardial effusion, significant coronary stent occlusion, poorly controlled deep venous thrombosis, etc).
  • Cardiovascular disease-related requirement for daily supplemental oxygen.
  • History of two or more myocardial infarctions OR two or more coronary revascularization procedures.
  • Subjects with history of myocarditis, regardless of etiology.
  • A confirmed history of encephalitis, meningitis, or uncontrolled seizures in the year prior to informed consent.
  • Participants with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days of enrollment. Inhaled or topical steroids, and adrenal replacement steroid doses >10 mg daily prednisone or equivalent, are permitted in the absence of active autoimmune disease.
  • Subjects with active central nervous system (CNS) metastases, active brain metastases or leptomeningeal metastatic foci. For the subjects with brain metastases, if they are asymptomatic, they are eligible to participate in this study. If participants have received treatment for brain metastases and have no clinical evidence of progressive disease at least 1 week after completion of treatment for brain metastases and within 28 days prior to the first dose of protocol-indicated treatment on this study, they are eligible to participate in this study.
  • Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
  • Known history of hepatitis B or hepatitis C.
  • Any significant medical condition, laboratory abnormality, or psychiatric illness, that would prevent the subject from participating in the study or place the subject at unacceptable risk if he/she were to participate in the study, or any condition that confounds the ability to interpret data from the study.
  • Subjects with life expectancy < 6 months.
  • Subjects receiving any other investigational or standard antineoplastic agents.
  • Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast.
  • Prisoners or participants who are involuntarily incarcerated.
  • Participants who are compulsorily detained for treatment of either a psychiatric or physical (e.g. infectious disease) illness.
  • Psychological, familial, sociological, or geographical conditions that potentially hamper compliance with the study protocol and follow-up schedule; those conditions should be discussed with the participant before registration in the trial.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Vanderbilt-Ingram Cancer Center

    Nashville, Tennessee, 37232

Other trials in United States

About this study

Official title: A Phase II Two-Arm Open-Label Study of Nivolumab Plus Relatlimab or Ipilimumab in Metastatic Melanoma Stratified by MHC-II Expression

This is an open-label, non-randomized two arm Phase 2 study of intravenous nivolumab plus intravenous ipilimumab or intravenous relatlimab in patients with metastatic melanoma stratified by MHC-II expression.

Read the detailed description

Primary Objective:

  • To evaluate the efficacy, measured by change in activated GZMB+ CD8+ T-cell density intratumorally, of two immunotherapy regimens in patients with advanced melanoma:
  • nivolumab plus relatlimab in patients with MHC-II (+) melanoma, and
  • nivolumab plus ipilimumab in patients with MHC-II (-) melanoma.

Secondary Objectives:

  • To evaluate the response rate, median progression free survival, overall survival, and safety and tolerability of nivolumab plus relatlimab in patients with MHC-II (+) melanoma, and of nivolumab plus ipilimumab in patients with MHC-II (-) melanoma.

Exploratory Objectives

  • To explore potential associations of biomarkers with clinical efficacy and/or incidence of adverse events due to study drug by analyzing biomarker measures within the peripheral blood and tumor microenvironment.
Being tested
Nivolumab, Relatlimab, Ipilimumab
Medical subject headings
Melanoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NivolumabDrug

    Nivolumab will be given by vein on day 1 of each cycle.

  • RelatlimabDrug

    Relatlimab will be given by vein on day 1 of each 28-day cycle

  • IpilimumabDrug

    Ipilimumab will be given by vein on day 1 during cycles 1-4 (cycles are 21 days).

Study groups in NCT03724968
Study groupRoleWhat they receive
Arm AExperimentalNivolumab and Relatlimab
Receives: Drug: Nivolumab; Drug: Relatlimab
Arm BExperimentalNivolumab and Ipilimumab
Receives: Drug: Nivolumab; Drug: Ipilimumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in Activated GZMB+ CD8+T-cell Density Intratumorally, of Two Immunotherapy Regimens

    Measured: Approximately 16 months

Secondary outcomes (4)

  1. Response Rate

    Measured: Approximately 16 months

  2. Median Progression Free Survival

    Measured: Approximately 16 months

  3. Median Overall Survival

    Measured: Approximately 16 months

  4. Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE Version 5.0

    Measured: Up to 30 days from last dose of drugs (average of 13 cycles)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Oct 2018
  2. Study start17 Jan 2019
  3. Primary completion28 May 2020
  4. Study completion28 May 2020

Why it stopped: Loss of funding

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
2 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03724968
Sponsor's protocol ID
VICC MEL 18114
Other IDs
NCI-2018-02469
Status last verified
Mar 2021
First submitted
26 Oct 2018
Last updated
20 Apr 2021
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Nivolumab, Relatlimab and Ipilimumab in people with Metastatic Melanoma and Advanced Melanoma, run by Elizabeth Davis at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 28 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 20 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 5 Mar 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Activated GZMB+ CD8+T-cell Density Intratumorally, of Two Immunotherapy Regimens (time frame: Approximately 16 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03724968.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Apr 2021.

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