Anti-Lag-3 (Relatlimab) and Anti-PD-1 Blockade (Nivolumab) Versus Standard of Care (Lomustine) for the Treatment of Patients With Recurrent Glioblastoma

Get Involved

Anti-Lag-3 (Relatlimab) and Anti-PD-1 Blockade (Nivolumab) Versus Standard of Care (Lomustine) for the Treatment of Patients With Recurrent Glioblastoma

Study Purpose

This phase II trial compares the safety, side effects and effectiveness of anti-lag-3 (relatlimab) and anti-PD-1 blockade (nivolumab) to standard of care lomustine for the treatment of patients with glioblastoma that has come back after a period of improvement (recurrent). Relatlimab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. 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, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Lomustine is a chemotherapy drug and in a class of medications called alkylating agents. It damages the cell's deoxyribonucleic acid and may kill tumor cells. Giving relatlimab and nivolumab may be safe, tolerable, and/or effective compared to standard of care lomustine in treating patients with recurrent glioblastoma.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years and Over
Gender	All

More Inclusion & Exclusion Criteria

Inclusion Criteria:

- Histologically-proven glioblastoma (World Health Organization [WHO] 2021 criteria) - Progressive or recurrent disease per Response Assessment in Neuro-Oncology (RANO) criteria.

- No IDH mutation (IDH1 R132H negative by immunohistochemistry [IHC] or sequencing) - Patients must be in first recurrence of glioblastoma following radiation therapy and temozolomide.

- No prior therapies except radiation, surgery, temozolomide, Tumor Treating Fields (TTFields), and/or Gliadel wafers (placed during the first surgery at diagnosis of glioblastoma multiforme [GBM]).

Prior radiation therapy, TTFields, or placement of Gliadel wafers must be completed at least 2 weeks prior to registration. Prior temozolomide must be completed at least 3 weeks prior to registration.

- No prior use of nivolumab or other anti-PD1 agents.

- Patients must be neurologically stable off corticosteroids for at least 5 days prior to registration.

- Age: ≥ 18 years.

- Karnofsky Performance Status: ≥ 60% (i.e. patient must be able to care for themselves with occasional help from others) - Absolute lymphocyte count (ALC): ≥ 1000/mm^3.

- Absolute neutrophil count (ANC): ≥ 1500/mm^3.

- Platelet count: ≥ 100,000/mm^3.

- Hemoglobin: ≥ 9.0 g/dL.

- Activated partial thromboplastin time (APTT) or partial thromboplastin time (PTT): ≤ 1.5 x upper limit of normal (ULN) - Total bilirubin: < 2.0 x ULN (Except for patients with Gilbert's syndrome, who must have direct bilirubin < 2.0 x ULN) - Aspartate aminotransferase (AST) / alanine aminotransferase (ALT): < 3.0 x ULN.

- Calculated (calc.

) creatinine clearance (CrCl): ≥ 50 mL/min.

- Calculated by Cockcroft-Gault equation.

- Not pregnant and not nursing, because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown and an agent that has known genotoxic, mutagenic and teratogenic effects.

Therefore, for women of childbearing potential only, a negative pregnancy test done within 14 days prior to registration is required.

- Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.

- No active brain metastases or leptomeningeal disease.

- HIV: HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months prior to registration are eligible for this trial.

- Hepatitis B: For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.

- Hepatitis C: Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured.

For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.

- No known medical condition causing an inability to swallow oral formulations of agents.

- No current symptomatic pulmonary disease.

- No autoimmune disorders that require systemic treatment (except hyperthyroidism or diabetes mellitus)

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT06325683
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 2
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	National Cancer Institute (NCI)
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Michael Lim
Principal Investigator Affiliation	Alliance for Clinical Trials in Oncology
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	NIH
Overall Status	Recruiting
Countries	United States
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Progressive Glioblastoma, Recurrent Glioblastoma

Additional Details

PRIMARY OBJECTIVE:

I. To compare the restricted mean survival time (RMST) for overall survival (OS) between patients receiving the combination of relatlimab (BMS-986016) and nivolumab versus patients receiving standard of care chloroethylcyclohexylnitrosourea (CCNU) (lomustine).

SECONDARY OBJECTIVES:

I. To compare the 12-month OS rates between patients receiving the combination of relatlimab (BMS-986016) and nivolumab versus patients receiving standard of care CCNU (lomustine).

II. To compare the restricted mean survival times for progression-free survival (PFS) between patients receiving the combination of relatlimab (BMS-986016) and nivolumab versus patients receiving standard of care CCNU (lomustine).

III. To compare the radiographic response rate between patients receiving the combination of relatlimab (BMS-986016) and nivolumab versus patients receiving standard of care CCNU (lomustine).

IV. To compare the safety/adverse event rate between patients receiving the combination of relatlimab (BMS-986016) and nivolumab versus patients receiving standard of care CCNU (lomustine).

OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive nivolumab intravenously (IV) over 30 minutes followed by relatlimab IV 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 surgery or biopsy, magnetic resonance imaging (MRI), and blood sample collection throughout study. ARM II: Patients receive lomustine orally (PO) on day 1 of each cycle. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo surgery or biopsy, MRI, and blood sample collection throughout study. After completion of study treatment, patients are followed up every 6 months for up to 5 years from time of randomization.

Arms & Interventions

Arms

Experimental: Arm I (nivolumab, relatlimab)

Patients receive nivolumab IV over 30 minutes followed by relatlimab IV 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 surgery or biopsy, MRI, and blood sample collection throughout study.

Active Comparator: Arm II (lomustine)

Patients receive lomustine PO on day 1 of each cycle. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo surgery or biopsy, MRI, and blood sample collection throughout study.

Interventions

Procedure: - Biopsy Procedure

Undergo biopsy

Procedure: - Biospecimen Collection

Undergo blood sample collection

Drug: - Lomustine

Given PO

Procedure: - Magnetic Resonance Imaging

Undergo MRI

Biological: - Nivolumab

Given IV

Biological: - Relatlimab

Given IV

Procedure: - Surgical Procedure

Undergo surgery

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Sutter Auburn Faith Hospital, Auburn 5325223, California 5332921

Status

Recruiting

Address

Sutter Auburn Faith Hospital

Auburn 5325223, California 5332921, 95602

Site Contact

Site Public Contact

Clinical Trial Finder