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

NCT04150965 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: MyCheckpoint (MMRC-089)
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 10

Brief 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 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.

Conditions

Multiple Myeloma; Relapsed Refractory Multiple Myeloma

Keywords

Multiple Myeloma; Relapsed; Refractory; MM; Multiple Myeloma Research Consortium; Multiple Myeloma Research Foundation; MMRC; MMRF

Outcome Measures

Primary Outcomes (2)

• 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).

  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.

• 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.

  Cycle 1 (28 days)

Study Arms (5)

Arm A - Elotuzumab

ACTIVE COMPARATOR

Patients receive Elotuzumab in combination with pomalidomide and dexamethasone. Arm A begings in Phase 2 portion.

Drug: Elotuzumab, pomalidomide, dexamethasone

Arm B - Anti LAG-3 Single Agent

EXPERIMENTAL

Patients receive Anti-LAG-3 as a single agent for 1 Cycle in Phase 1 portion.

Drug: Anti-LAG-3

Arm B:Combination Anti LAG-3 +Pomalidomide+Dexamethasone

EXPERIMENTAL

Cycle 2 and beyond Patients receive Anti-LAG-3 in combination with pomalidomide and dexamethasone.

Drug: Anti-LAG-3 + Pomalidimide + Dexamethasone

Arm C - Anti-TIGIT Single Agent

EXPERIMENTAL

Patients receive Anti-TIGIT as a single agent for 1 Cycle in Phase 1 portion.

Drug: Anti-TIGIT

ARM C: Anti-TIGIT +Pomalidomide+Dexamethasone

EXPERIMENTAL

Cycle 2 and beyond Patients receive Anti-TIGIT in combination with pomalidomide and dexamethasone.

Drug: Anti-TIGIT + Pomalidimide + Dexamethasone

Interventions

Elotuzumab, pomalidomide, dexamethasone DRUG

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.

Also known as: Empliciti

Arm A - Elotuzumab

Anti-LAG-3 DRUG

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.

Also known as: BMS-986016, Anti LAG-3, Relatlimab

Arm B - Anti LAG-3 Single Agent

Anti-LAG-3 + Pomalidimide + Dexamethasone DRUG

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.

Also known as: BMS-986016, Anti-LAG-3, Pomalidomide, Dexamethasone

Arm B:Combination Anti LAG-3 +Pomalidomide+Dexamethasone

Anti-TIGIT DRUG

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

Also known as: BMS-986207

Arm C - Anti-TIGIT Single Agent

Anti-TIGIT + Pomalidimide + Dexamethasone DRUG

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

Also known as: BMS-986207

ARM C: Anti-TIGIT +Pomalidomide+Dexamethasone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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
• 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;
• \. 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;

Sponsors & Collaborators

• Multiple Myeloma Research Consortium: lead
• Bristol-Myers Squibb: collaborator
• Emory University: collaborator
• Washington University School of Medicine: collaborator
• Beth Israel Deaconess Medical Center: collaborator
• Dana-Farber Cancer Institute: collaborator
• Wake Forest University Health Sciences: collaborator
• Memorial Sloan Kettering Cancer Center: collaborator
• Icahn School of Medicine at Mount Sinai: collaborator
• University of Texas: collaborator
• Hackensack Meridian Health: collaborator
• University of Michigan: collaborator

Study Sites (10)

Emory University

Atlanta, Georgia, 30322, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02115, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Washington University School of Medicine Division of Medical Oncology

St Louis, Missouri, 63110, United States

Location

Hackensack Meridian Medical Center

Hackensack, New Jersey, 07601, United States

Location

Mount Sinai School of Medicine

New York, New York, 10029, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

Location

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Related Publications (1)

• 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.

  PMID: 39187595 DERIVED

MeSH Terms

Conditions

Multiple Myeloma; Recurrence

Interventions

elotuzumab; pomalidomide; Dexamethasone; relatlimab

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Madhav V. Dhodapkar, M.D.

  Medical Monitor

  PRINCIPAL INVESTIGATOR

• Hearn J. Cho, M.D., Ph.D.

  Chief Medical Officer

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: November 1, 2019
• First Posted: November 5, 2019
• Study Start: July 10, 2020
• Primary Completion: August 30, 2024
• Study Completion: August 30, 2024
• Last Updated: February 14, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (10)