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Multiple MyelomaPhase 1/2NCT04150965

Immuno-Oncology Drugs Elotuzumab, Anti-LAG-3 and Anti-TIGIT

A Phase 1/2 study testing Elotuzumab, pomalidomide, dexamethasone, Anti-LAG-3 and Anti-LAG-3 + Pomalidimide + Dexamethasone in people with Multiple Myeloma and Relapsed Refractory Multiple Myeloma, run by Multiple Myeloma Research Consortium at 10 sites 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 a Phase I/II randomized trial for patients with relapsed refractory Multiple Myeloma who have relapsed after treatment with prior therapies. The protocol is designed to evaluate two agents, Anti-LAG-3 and Anti-TIGIT, in order to understand their immunologic effects and safety both as single agents and in… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Elotuzumab, pomalidomide, dexamethasone, Anti-LAG-3 and Anti-LAG-3 + Pomalidimide + Dexamethasone
Could I receive a placebo?
No, everyone receives an active treatment
How many people
14 participants
Where
10 sitesUnited States
Study dates
10 Jul 2020to 30 Aug 2024
Phase
Phase 1/2
Are there results?
None posted in the registry

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

  • 18 years of age or greater.
  • Willing and able to provide informed consent
  • Patient has received at least 3 prior lines of therapy and must have received prior therapy including at least one drug from each drug class; IMiD, proteasome inhibitors, and anti-CD38 monoclonal antibody.
  • The following laboratory values obtained ≤ 14 days prior to initiation of therapy:
  • ANC ≥ 1000/ul (without growth factor support within 14 days of initiation of therapy)
  • Hgb ≥ 8 g/dl
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  • PLT ≥ 75,000/ul (without transfusion support within 14 days of initiation of therapy)
  • Total bilirubin <1.5 x upper limit of normal (ULN) or if total bilirubin is ≥1.5 x ULN, the direct bilirubin must be ≤ 2.0 mg/dL (patients with Gilberts syndrome may have total bilirubin ≤3.0 x ULN
  • AST and ALT < 2.5x ULN
  • Creatinine Clearance ≥ 30 mL/min by Cockcroft Gault Equation
  • Measurable disease of MM as defined by at least ONE of the following:
  • Serum monoclonal protein ≥1.0 g by protein electrophoresis
  • ≥200 mg of monoclonal protein in the urine on 24-hour electrophoresis
  • Serum immunoglobulin FLC ≥10 mg/dL AND abnormal serum immunoglobulin kappa to lambda FLC ratio.
  • Normal thyroid function, or stable on hormone supplementation per investigator assessment.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status 0, 1, or 2.
  • Willingness to return to enrolling institution for follow-up.
  • Disease free of prior malignancies for ≥ 3 year with exception of currently treated basal cell, squamous cell carcinoma of the skin, carcinoma "insitu" of the cervix or breast, or prostate cancer not requiring therapy
  • Ability to understand the purpose and risks of the study and provide signed and dated ICF and authorization to use protected health information.
  • All study participants must be willing to be registered into, and comply with, the mandatory pomalidomide (POMALYST®) Risk Evaluation and Mitigation Strategy (REMS®) program and be willing to use contraception 28 days prior to pomalidomide treatment and continue until 120 days after the last dose of pomalidomide.
  • Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation. For patient's intolerant to aspirin or for high-risk patients with prior history of thromboembolic events, thromboprophylaxis with other anti-coagulants agents, including low molecular weight heparin, warfarin, or novel oral anticoagulants such as apixaban or rivaroxaban, is allowed.
  • All females of child bearing potential (FCBP)* must have a negative pregnancy test (urine or serum) documented ≤7 days prior to start of therapy with repeat pregnancy test on Day 1 of each cycle and at the EoT visit. Note: Additional pregnancy testing is required as a condition of the POMALYST REMS® program prior to and while on treatment and following the last dose of pomalidomide. FCBP must have 2 negative pregnancy tests prior to initiating pomalidomide treatment. The first test should be performed within 10-14 days prior to prescribing POMALYST and the second test within 24 hours prior to prescribing POMALYST therapy and then weekly during the first 4 weeks, then every 4 weeks thereafter in females with regular menstrual cycles, or every 2 weeks in females with irregular menstrual cycles. Protocol section 8.1 provides guidelines on the use and required time frames of contraception. NOTE: *A female of childbearing potential (FCBP) is a sexually mature female who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).

Who cannot join

  • Patient is known to be human immunodeficiency virus (HIV) positive, Hepatitis B surface antigen-positive, Hep B PCR positive or active Hepatitis C infection
  • Pregnant or breast feeding females;
  • Any clinically significant, uncontrolled medical conditions including, but not limited to, myocardial infarction or stroke/transient ischemic attack within the past 6 months, uncontrolled angina within the past 3 months, symptomatic congestive heart failure, cardiac arrhythmia (such as ventricular tachycardia, ventricular fibrillation, or torsades de pointes), pericarditis, myocarditis, cardiomyopathy, requirement for supplemental oxygen;
  • Any psychiatric illness/social situations that, in the Investigator's opinion, would impose excessive risk to the patient or may interfere with compliance or interpretation of the study results;
  • QT interval corrected for heart rate using Fridericia's formula (QTcF) prolongation > 480 msec, except for right bundle branch block;
  • Ongoing or active infection, that requires systemic antibacterial, antiviral, or antifungal therapy < 7 days prior to the initiation of therapy
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  • Inability to tolerate thromboprophylaxis ;
  • Known CNS involvement;
  • Known severe intolerance to steroid therapy (Grade 3 or above adverse event unresponsive to dose reduction and/or per investigators discretion);
  • History of autoimmune disease, requiring therapy including but not limited to systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Bell's palsy, Guillain-Barré syndrome, multiple sclerosis, vasculitis, glomerulonephritis, or suspected autoimmune disease. (Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, euthyroid with a history of Grave's disease (participants with suspected autoimmune thyroid disorders must be negative for thyroglobulin and thyroid peroxidase antibodies and thyroid stimulating Ig prior to the first dose of study drug), psoriasis not requiring systemic treatment, well controlled asthma and/or mild allergic rhinitis [seasonal allergies], or conditions not expected to recur in the absence of an external trigger);
  • NYHA Classification > Class 2;
  • Concurrent amyloidosis, plasma cell leukemia or POEMS syndrome [plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein (M-protein) and skin changes;
  • History of erythema multiforme or severe (≥ grade 3) hypersensitivity to prior IMiD's;
  • 14. Anti-cancer therapy within the specified time frames prior to initiation of therapy: cytotoxic investigational agents, within 3 weeks (6 weeks for nitrosoureas), IMiDs, Proteosome inhibitors or corticosteroids within 2 weeks, investigational therapies within 14 days or 5 half-lives of the investigational drug, whichever is longer, and monoclonal antibodies within 4 weeks, bispecifics (antibodies) within 4 weeks, CAR-T within 4 weeks post infusion. Prednisone up to but no more than 10 mg orally q.d. or its equivalent for symptom management of comorbid conditions is permitted but dose should be stable for at least 7 days. Live vaccines within 30 days (The inactivated seasonal influenza vaccine can be given to patients before treatment and while on therapy without restriction). Shorter time lines may be considered in consultation with the PI;
  • Prior major surgery or radiation therapy within 4 weeks of initiation of therapy;
  • Prior therapy with Anti-TIGIT or Anti-LAG-3 ; Elotuzumab
  • Any > Grade 1 adverse reaction unresolved from previous treatments according to the NCI CTC AE v 5.0. The presence of alopecia or peripheral neuropathy ≤ Grade 2 without pain is allowed;
  • Previous allogeneic stem cell transplantation;
  • Immunosuppressive therapy in the last 2 months prior to initiation of therapy;
  • Autologous stem cell transplant if < 12 weeks from initiation of therapy;
  • History of idiopathic pulmonary fibrosis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.);
  • Cardiac Troponin T (cTnT) or I(cTnI)≥2×institutional ULN.
  • Subjects with cTnT or cTnI levels between > 1 to 2 × ULN will be permitted if repeat levels within 24 hours are ≤ 1 ULN
  • If cTnT or cTnI levels are >1 ULN at 24 hours, the subject may undergo a cardiac evaluation and be considered for treatment, following a discussion with the Principal Investigator.

Trial locations and contacts

10 sites in 1 country.

10 sites in 1 country

United States10 sites

  • University of Michigan

    Ann Arbor, Michigan, 48109

  • Emory University

    Atlanta, Georgia, 30322

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02115

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02115

  • Levine Cancer Institute

    Charlotte, North Carolina, 28204

  • UT Southwestern Medical Center

    Dallas, Texas, 75390

  • Hackensack Meridian Medical Center

    Hackensack, New Jersey, 07601

  • Mount Sinai School of Medicine

    New York, New York, 10029

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • Washington University School of Medicine Division of Medical Oncology

    St Louis, Missouri, 63110

Other trials in United States

About this study

Official title: A Phase I/II Assessment of Combination Immuno-Oncology Drugs Elotuzumab, Anti-LAG-3 (BMS-986016) and Anti-TIGIT (BMS-986207)

This a Phase I/II randomized trial for patients with relapsed refractory Multiple Myeloma who have relapsed after treatment with prior therapies. The protocol is designed to evaluate two agents, Anti-LAG-3 and Anti-TIGIT, in order to understand their immunologic effects and safety both as single agents and in combination with pomalidomide and dexamethasone. In these arms, patients will be treated with either Anti-LAG-3 or Anti-TIGIT respectively for one cycle as single agent followed by the addition of pomalidomide and dexamethasone in combination for subsequent cycles.

A third arm allows patients to be treated with the FDA approved combination of elotuzumab plus pomalidomide and dexamethsone as a control. This arm will thus allow a concurrent standard of care comparator for the experimental arms.

Read the detailed description

This study will enroll 104 patients to one of three treatment arms. The study is open to patients relapsing with refractory Multiple Myeloma who have:

  • received 3 prior lines of therapy
  • exposed to each of these 3 drug classes:
  • IMiD
  • proteasome inhibitors, and
  • anti-CD38 monoclonal antibody
  • relapsed and refractory are defined using the IMWG criteria:
  • disease that is non-responsive while on salvage therapy or progresses within 60 days of last therapy in patients who have achieved minimal response or better at some point previously to then progressing in their disease course.
Being tested
Elotuzumab, pomalidomide, dexamethasone, Anti-LAG-3, Anti-LAG-3 + Pomalidimide + Dexamethasone, Anti-TIGIT, Anti-TIGIT + Pomalidimide + Dexamethasone
Keywords
Multiple Myeloma, Relapsed, Refractory, MM, Multiple Myeloma Research Consortium, Multiple Myeloma Research Foundation, MMRC, MMRF
Medical subject headings
Multiple Myeloma, Recurrence

What participants receive

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

  • Elotuzumab, pomalidomide, dexamethasoneDrug

    Also called Empliciti

    Study Patients with relapsed Multiple Myeloma will receive: Elotuzumab, Pomalidomide, and Dexamethasone Starting in Phase 2 Cycle 1 Day 1 forward. Each cycle is 28 days long.

  • Anti-LAG-3Drug

    Also called BMS-986016, Anti LAG-3, Relatlimab

    Patients with relapsed Multiple Myeloma will receive: Anti -LAG-3 single agent for Cycle 1. Each Cycle is 28 days

    Cycle 2 forward patients will receive Anti-LAG-3 in combination with pomalidomide and dexamethasone from Cycle 2 forward. Each cycle is 28 days long.

  • Anti-LAG-3 + Pomalidimide + DexamethasoneDrug

    Also called BMS-986016, Anti-LAG-3, Pomalidomide, Dexamethasone

    Patients with Relapsed \& Refractory Multiple Myeloma will receive: Anti-LAG-3 in combination with pomalidomide and dexamethasone from Cycle 2 forward. Each cycle is 28 days.

  • Anti-TIGITDrug

    Also called BMS-986207

    Patients with relapsed Multiple Myeloma will receive: Anti -TIGIT single agent for Cycle 1.

    Each cycle is 28 days.

  • Anti-TIGIT + Pomalidimide + DexamethasoneDrug

    Also called BMS-986207

    Cycle 2 and beyond patients will receive Anti-TIGIT in combination with pomalidomide and dexamethasone from Cycle 2 forward. Each cycle is 28 days..

Study groups in NCT04150965
Study groupRoleWhat they receive
Arm A - ElotuzumabActive comparatorPatients receive Elotuzumab in combination with pomalidomide and dexamethasone. Arm A begings in Phase 2 portion.
Receives: Drug: Elotuzumab, pomalidomide, dexamethasone
Arm B - Anti LAG-3 Single AgentExperimentalPatients receive Anti-LAG-3 as a single agent for 1 Cycle in Phase 1 portion.
Receives: Drug: Anti-LAG-3
Arm B:Combination Anti LAG-3 +Pomalidomide+DexamethasoneExperimentalCycle 2 and beyond Patients receive Anti-LAG-3 in combination with pomalidomide and dexamethasone.
Receives: Drug: Anti-LAG-3 + Pomalidimide + Dexamethasone
Arm C - Anti-TIGIT Single AgentExperimentalPatients receive Anti-TIGIT as a single agent for 1 Cycle in Phase 1 portion.
Receives: Drug: Anti-TIGIT
ARM C: Anti-TIGIT +Pomalidomide+DexamethasoneExperimentalCycle 2 and beyond Patients receive Anti-TIGIT in combination with pomalidomide and dexamethasone.
Receives: Drug: Anti-TIGIT + Pomalidimide + Dexamethasone

What is being measured

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

  1. Overall Response Rate

    The overall response rate of the drug combination, in each Arm for RRMM, which is defined as the proportion of subjects who achieved a response (≥ VGPR).

    Measured: Patients will be evaluated monthly for response from the start of the study until the date of documented disease progression, assessed up to 18 months.

  2. Frequency, type and grade of Adverse Events and Serious Adverse Events

    Frequency, type and grade of Adverse Events and Serious Adverse Events during Cycle 1 of Single agent Arms B and C. In Combination for all Arms.

    Measured: Cycle 1 (28 days)

Timeline

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

  1. First posted5 Nov 2019
  2. Study start10 Jul 2020
  3. Primary completion30 Aug 2024
  4. Study completion30 Aug 2024

Why it stopped: Pharmaceutical support has been discontinued.

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 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Sequential
Model description
The trial is designed for patients with functionally high-risk MM (early relapse after initial therapy as defined above), who will be assigned to a targeted agent in the presence of an actionable mutation or an agent in the absence of an actionable genetic alteration, both in combination with a common backbone. This is a MMRC Sponsored multicenter, open label Phase 1/2 study of several different drugs in patients with relapsed myeloma, with treatment assignment guided by genomic studies.
Masking
None (open label)
Enrolment
14 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04150965
Sponsor's protocol ID
MyCheckpoint (MMRC-089)
Status last verified
Feb 2025
First submitted
1 Nov 2019
Last updated
14 Feb 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Richard S, Lesokhin AM, Paul B, Kaufman JL, Pianko M, Biran N, Vij R, Doxie DB, Azeem MI, Martillo M, Wozniak K, Cho HJ, Dhodapkar KM, Dhodapkar MV. Clinical response and pathway-specific correlates following TIGIT-LAG3 blockade in myeloma: the MyCheckpoint randomized clinical trial. Nat Cancer. 2024 Oct;5(10):1459-1464. doi: 10.1038/s43018-024-00818-w. Epub 2024 Aug 26.

    PubMed 39187595

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Elotuzumab, pomalidomide, dexamethasone, Anti-LAG-3 and Anti-LAG-3 + Pomalidimide + Dexamethasone in people with Multiple Myeloma and Relapsed Refractory Multiple Myeloma, run by Multiple Myeloma Research Consortium at 10 sites 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 22 inclusion and 24 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 14 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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?

The study was stopped early (reason given: Pharmaceutical support has been discontinued.). Results are not available in the source record.

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?

Overall Response Rate (time frame: Patients will be evaluated monthly for response from the start of the study until the date of documented disease progression, assessed up to 18 months.). The study lists 2 primary outcomes in all. 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 NCT04150965, which also lists 1 linked publication.

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 14 Feb 2025.

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