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Advanced LymphomaPhase 2NCT06400264

Testing Nivolumab and BMS-986016 (Relatlimab) as Potentially Targeting Treatment in Cancers That Are LAG-3+ and Have Mismatch Repair Deficiency (MATCH - Subprotocol Z1M)

A Phase 2 study testing Biopsy, Biospecimen Collection and Computed Tomography in people with Advanced Lymphoma and Advanced Malignant Solid Neoplasm, run by National Cancer Institute (NCI).

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

This phase II MATCH treatment trial tests how well nivolumab and BMS-986016 (relatlimab) works in treating patients with cancer that has certain genetic changes called LAG-3 mutations with mismatch repair deficiency. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Biopsy, Biospecimen Collection and Computed Tomography
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
22 Feb 2022to 17 Jan 2023
Phase
Phase 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

  • Patients must have met applicable eligibility criteria in the Master MATCH Protocol EAY131/ NCI-2015-00054 prior to registration to treatment subprotocol
  • Patients must fulfill all eligibility criteria of MATCH Master Protocol at the time of registration to treatment step (Step 1, 3, 5, 7)
  • Patients must have mismatch repair deficiency based on one of the following:
  • Mismatch repair testing done in any laboratory under Clinical Laboratory Improvement Act (CLIA) conditions with immunohistochemistry (IHC) for MLH1/MSH2 +/-MSH6 +/-PMS2 OR
  • Polymerase chain reaction (PCR)-based microsatellite testing using a validated assay done in any laboratory under CLIA conditions OR
  • A MATCH designated laboratory determination of mismatch repair (MMR) status by deoxyribonucleic acid (DNA) sequencing
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  • Patients must have LAG-3 expression at >= 1% as determined via the MATCH Master Protocol
  • NOTE: For patients entering the study, all patients must have LAG-3 testing performed as described in the MATCH Master Protocol. This includes patients entering the study via the outside assay process
  • Patients with active melanoma are ineligible
  • Patients must have an electrocardiogram (ECG) within 8 weeks prior to treatment assignment and must have no clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g. complete left bundle branch block, third degree heart block)
  • Patients must have Troponin T (TnT) or I (TnI) < 2 x upper limit of normal (ULN). Patients with TnT or TnI levels between > 1 to 2 x ULN will be allowed to register if repeat levels within 24 hours are =< 1 x ULN. If TnT or TnI levels are > 1 to 2 x ULN within 24 hours, the patients may undergo a cardiac evaluation and be considered for treatment. 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 < 2 x ULN, the patient may undergo cardiac evaluation and be considered for treatment
  • Patients must not have known hypersensitivity to nivolumab and BMS-986016 or compounds of similar chemical or biologic composition
  • Patients must not have a history of severe hypersensitivity reaction to any monoclonal antibody
  • Patients must have had prior therapy on PD-1/PD-L1 therapy with progression on therapy or within 6 months of completion of PD-1/PD-L1 inhibitor therapy
  • Patients must not have a history of toxic epidermal necrolysis (Stevens-Johnson syndrome)
  • Patients must not have received growth factors, including but not limited to granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), erythropoietin, etc. within 2 weeks of study drug administration. Use of such agents while on study is also prohibited. Prior use of growth factors should be documented in the patient's medical history
  • Patients must not have a history of any autoimmune disease: inflammatory bowel disease, (including ulcerative colitis and Crohn's disease), rheumatoid arthritis, systemic progressive sclerosis (scleroderma), systemic lupus erythematosus (SLE) autoimmune vasculitis (e.g., Wegener's granulomatosis), central nervous system (CNS) or motor neuropathy considered to be of autoimmune origin (e.g., Guillian-Barre syndrome, myasthenia gravis, multiple sclerosis). Patients are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger (precipitating event). Entry of patients with autoimmune diagnoses not listed here must be approved by the protocol chair
  • Patients must not be on supplemental home oxygen
  • Patients must not have prior treatment with anti-LAG3 inhibitors
  • Patients must not have evidence of interstitial lung disease
  • Patients with a requirement for steroid treatment or other immunosuppressive treatment: Patients will be excluded if they have a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
  • Patients must not not expect to conceive or father children by using accepted and effective method(s) of contraception or by abstaining from sexual intercourse for at least one week prior to the start of treatment and for the duration of study participation. Patients of childbearing potential must continue to use accepted and effective methods of contraception for 5 months after the last dose of protocol treatment. In addition, patients of childbearing potential must have a negative serum pregnancy test within 2 weeks prior to registration with a minimum sensitivity of at least 50 IU/L and it must be repeated within 24 hours prior to the first dose of nivolumab and BMS-986016. Patients must also not donate sperm while on study treatment. These supersede the requirements in the EAY131 MASTER protocol eligibility section regarding pregnancy testing and contraception requirements.
  • Patients with hepatitis B virus (HBV) or hepatitis C virus (HCV) infection may be eligible provided they have the following:
  • There must be no evidence of clinically significant hepatic injury from hepatitis virus infection
  • For HBV, patients must be on suppressive therapy and have undetectable HBV viral load
  • For HCV, patients must either be on suppressive therapy for HCV or have already completed therapy thought to have eradicated HCV
  • Patients must meet one of the following criteria:
  • Patients must have tumor amenable to image guided or direct vision biopsy and be willing and able to undergo a tumor biopsy to obtain tissue for research. Biopsy must not be considered to be more than minimal risk to the patient OR
  • Patient will be undergoing a procedure due to medical necessity prior to start of treatment during which the tissue may be collected OR
  • Formalin-fixed paraffin-embedded tumor tissue block(s) or unstained sectioned slides are available for submission following pre-registration. Criteria for the submission of formalin-fixed paraffin-embedded (FFPE) tissue are:
  • Tissue must have been collected within 6 months prior to pre-registration to step 0
  • Collection of the tissue was after the completion of PD-1/PD-L1 therapy
  • Formalin-fixed paraffin-embedded tumor tissue block(s) must meet the minimum requirements outlined in the Master Protocol.
  • NOTE: If tissue submitted for central LAG-3 testing meets this criteria, additional tissue is not necessary

Who cannot join

None listed.

About this study

Official title: MATCH Treatment Subprotocol Z1M: Phase 2 Study of Nivolumab and BMS-986016 (Relatlimab) in Patients With LAG-3+ Tumors With Mismatch Repair Deficiency (MMR-d) After Progression on Anti-PD-1/PD-L1 Therapy

This phase II MATCH treatment trial tests how well nivolumab and BMS-986016 (relatlimab) works in treating patients with cancer that has certain genetic changes called LAG-3 mutations with mismatch repair deficiency. A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Immunotherapy with monoclonal antibodies, such as nivolumab and BMS-986016 (relatlimab), may help the body's immune system attack the cancer, and may interfere with the ability of cancer cells to grow and spread.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To evaluate the proportion of patients with objective response (OR) to targeted study agent(s) in patients with advanced refractory cancers/lymphomas/multiple myeloma.

SECONDARY OBJECTIVES:

  1. To evaluate the proportion of patients alive and progression free at 6 months of treatment with targeted study agent in patients with advanced refractory cancers/lymphomas/multiple myeloma.

II. To evaluate time until death or disease progression. III. To identify potential predictive biomarkers beyond the genomic alteration by which treatment is assigned or resistance mechanisms using additional genomic, ribonucleic acid (RNA), protein and imaging-based assessment platforms.

IV. To assess whether radiomic phenotypes obtained from pre-treatment imaging and changes from pre- through post-therapy imaging can predict objective response and progression free survival and to evaluate the association between pre-treatment radiomic phenotypes and targeted gene mutation patterns of tumor biopsy specimens.

OUTLINE:

Patients receive nivolumab intravenously (IV) over 30 minutes on day 1 and BMS-986016 (relatlimab) over 30 minutes on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo computed tomography (CT) or magnetic resonance imaging (MRI) during screening and on study, as well as during follow-up as clinically necessary. Patients also undergo echocardiography (ECHO) during screening as clinically indicated. Patients undergo a biopsy during screening and blood sample collection during screening and on study.

After completion of study treatment, patients are followed every 3 months for 2 years and then every 6 months for 1 year.

Being tested
Biopsy, Biospecimen Collection, Computed Tomography, Echocardiography, Magnetic Resonance Imaging
Medical subject headings
Lymphoma, Multiple Myeloma

What participants receive

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

  • BiopsyProcedure or surgery

    Also called BIOPSY_TYPE, Bx

    Undergo biopsy

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection

    Undergo blood sample collection

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo CT scan

  • EchocardiographyProcedure or surgery

    Also called EC

    Undergo ECHO

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan

    Undergo MRI

  • NivolumabBiological

    Also called ABP 206, BCD-263, BMS-936558, CMAB819

    Given IV

  • RelatlimabBiological

    Also called BMS-986016, BMS986016, Immunoglobulin G4, Anti-(human Lymphocyte Activation Gene-3 Protein) (Human Heavy Chain), Disulfide with Human Light Chain, Dimer

    Given IV

Study groups in NCT06400264
Study groupRoleWhat they receive
Treatment (nivolumab and BMS-986016 [relatlimab])ExperimentalPatients receive nivolumab IV over 30 minutes on day 1 and BMS-986016 (relatlimab) over 30 minutes on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT or MRI during screening and on study, as well as during follow-up as clinically necessary. Patients also undergo ECHO during screening as clinically indicated. Patients undergo a biopsy during screening and blood sample collection during screening and on study.
Receives: Procedure: Biopsy; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Echocardiography; Procedure: Magnetic Resonance Imaging; Biological: Nivolumab; Biological: Relatlimab

What is being measured

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

  1. Objective response rate (ORR)

    ORR is defined as the percentage of patients whose tumors have a complete or partial response to treatment among analyzable patients. Objective response is defined consistent with Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. 90% two-sided confidence interval is calculated for ORR. For the purposes of this study, patients should be re-evaluated for response:

    • For treatments given in 21 day (3 week) cycles: every 3 cycles (9 weeks) for the first 33 cycles, and every 4 cycles thereafter (12 weeks)
    • For treatments given in 28 day (4 week) cycles: every 2 cycles (8 weeks) for the first 26 cycles, and every three cycles thereafter (12 weeks)
    • For treatments given in 42 day (6 week) cycles: every 2 cycles (12 weeks)

    Measured: Up to 3 years

Secondary outcomes (3)

  1. Overall survival (OS)

    Will be evaluated specifically for each drug (or step). OS will be estimated using the Kaplan-Meier method.

    Measured: From start of treatment on that step until death, or censored at the date of last contact, assessed up to 3 years

  2. 6-month progression free survival (PFS)

    Progression free survival is defined as time from treatment start date to date of progression or death from any cause, whichever occurs first. Disease progression was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. Please refer to the protocol for detailed definitions of disease progression. 6 month PFS rate was estimated using the Kaplan-Meier method, which can provide a point estimate for any specific time point.

    Measured: From start of treatment on that step until determination of disease progression or death from any cause, censored at the date of last disease assessment for patients who have not progressed, assessed at 6 months

  3. Progression free survival

    PFS was defined as time from treatment start date to date of disease progression or death from any causes, whichever occurred first. Median PFS was estimated using the Kaplan-Meier method. Disease progression was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. Please refer to the protocol for detailed definitions of disease progression.

    Measured: From start of treatment on that step until determination of disease progression or death from any cause, censored at the date of last disease assessment for patients who have not progressed, assessed up to 3 years

Timeline

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

  1. First posted6 May 2024
  2. Study start22 Feb 2022
  3. Primary completion17 Jan 2023
  4. Study completion17 Jan 2023

Why it stopped: No result will be reported- no patient accrued. Status Withdrawn: Study halted prematurely, prior to enrollment of first participant."

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06400264
Sponsor's protocol ID
NCI-2024-01195
Other IDs
NCI-2024-01195, EAY131-Z1M, EAY131-Z1M, U10CA180820
Status last verified
Apr 2024
First submitted
3 May 2024
Last updated
6 May 2024
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Biopsy, Biospecimen Collection and Computed Tomography in people with Advanced Lymphoma and Advanced Malignant Solid Neoplasm, run by National Cancer Institute (NCI).

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 34 inclusion and 0 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: withdrawn, as of the sponsor's last update on 6 May 2024. Status can change between updates, so confirm with the study contact before making plans.

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?

The study was withdrawn before enrolling participants, so there are no results.

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?

Objective response rate (ORR) (time frame: Up to 3 years). 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 NCT06400264.

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 6 May 2024.

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