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

NCT06400264 | Withdrawn Phase 2 FDA Drug

• 3 other identifiers: NCI-2024-01195EAY131-Z1MU10CA180820
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief 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. 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.

Conditions

Advanced Lymphoma; Advanced Malignant Solid Neoplasm; Refractory Lymphoma; Refractory Malignant Solid Neoplasm; Refractory Multiple Myeloma

Outcome Measures

Primary Outcomes (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)

  Up to 3 years

Secondary Outcomes (3)

• Overall survival (OS)

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

• 6-month progression free survival (PFS)

  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

• Progression free survival

  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

Study Arms (1)

Treatment (nivolumab and BMS-986016 [relatlimab])

EXPERIMENTAL

Patients 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.

Procedure: Biopsy; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Procedure: Echocardiography; Procedure: Magnetic Resonance Imaging; Biological: Nivolumab; Biological: Relatlimab

Interventions

Biopsy PROCEDURE

Undergo biopsy

Also known as: BIOPSY_TYPE, Bx

Treatment (nivolumab and BMS-986016 [relatlimab])

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (nivolumab and BMS-986016 [relatlimab])

Computed Tomography PROCEDURE

Undergo CT scan

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, tomography

Treatment (nivolumab and BMS-986016 [relatlimab])

Echocardiography PROCEDURE

Undergo ECHO

Also known as: EC

Treatment (nivolumab and BMS-986016 [relatlimab])

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Treatment (nivolumab and BMS-986016 [relatlimab])

Nivolumab BIOLOGICAL

Given IV

Also known as: ABP 206, BCD-263, BMS-936558, CMAB819, MDX-1106, NIVO, Nivolumab Biosimilar ABP 206, Nivolumab Biosimilar BCD-263, Nivolumab Biosimilar CMAB819, ONO-4538, Opdivo

Treatment (nivolumab and BMS-986016 [relatlimab])

Relatlimab BIOLOGICAL

Given IV

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

Treatment (nivolumab and BMS-986016 [relatlimab])

Eligibility Criteria

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

You may qualify if:

• 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
• 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)

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

MeSH Terms

Conditions

Lymphoma; Multiple Myeloma

Interventions

Biopsy; Specimen Handling; Magnetic Resonance Spectroscopy; Nivolumab; relatlimab; Immunoglobulin G; Disulfides

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Spectrum Analysis; Chemistry Techniques, Analytical; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immunoglobulin Isotypes; Sulfides; Anions; Ions; Electrolytes; Inorganic Chemicals; Hydrogen Sulfide; Sulfur Compounds; Organic Chemicals

Study Officials

• Nilofer S Azad

  ECOG-ACRIN Cancer Research Group

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 3, 2024
• First Posted: May 6, 2024
• Study Start: February 22, 2022
• Primary Completion: January 17, 2023
• Study Completion: January 17, 2023
• Last Updated: May 6, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will share