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NCT06029270PHASE2Recruiting

Testing the Addition of BMS-986016 (Relatlimab) to the Usual Immunotherapy After Initial Treatment for Recurrent or Metastatic Nasopharyngeal Cancer

National Cancer Institute (NCI)

Start Date

7/15/2024

Completion Date

4/30/2029

Summary

This phase II trial tests the addition of BMS-986016 (relatlimab) to the usual immunotherapy after initial treatment for nasopharyngeal cancer that has come back after a period of improvement (recurrent) or that has spread from where it first started (primary site) to other places in the body (metastatic). Relatlimab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. The usual approach of treatment is initial treatment with chemotherapy such as the combination of cisplatin (or carboplatin) and gemcitabine, along with immunotherapy such as nivolumab. After the initial treatment is finished, patients may continue to receive additional immunotherapy. Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of tumor cells. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Gemcitabine is a chemotherapy drug that blocks the cells from making deoxyribonucleic acid (DNA) and may kill cancer cells. Giving BMS-986016 in addition to the usual immunotherapy after initial treatment may extend the time without the tumor cells growing or spreading longer than the usual approach in patients with recurrent or metastatic nasopharyngeal cancer.

Detailed Description

PRIMARY OBJECTIVE: I. To determine if adding BMS-986016 (relatlimab) to nivolumab maintenance therapy shows a signal of improved progression-free survival (PFS) according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 in patients who do not progress following treatment with platinum-gemcitabine-nivolumab combination in the first-line treatment of recurrent and/or metastatic nasopharyngeal carcinoma (R/M NPC). SECONDARY OBJECTIVES: I. To determine if adding BMS-986016 (relatlimab) to nivolumab maintenance improves overall survival (OS) compared to nivolumab maintenance alone. II. To compare patterns of failure (local-regional relapse and distant metastasis) between treatment arms. III. To determine if adding BMS-986016 (relatlimab) to nivolumab maintenance improves objective response, duration of response, and disease control rate compared to nivolumab maintenance alone. IV. To evaluate the tolerability of nivolumab-BMS-986016 (relatlimab) maintenance and assess and compare toxicity between arms based on the Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0) criteria. V. To evaluate baseline plasma Epstein-Barr virus (EBV) DNA (\< 2000 copies/mL versus \[vs.\] \>= 2000 copies/mL) as a prognostic biomarker. VI. To validate post-induction plasma EBV DNA (detectable \[\>= 1 copies/mL\] vs. undetectable \[0 copies/mL\]) as a prognostic biomarker. EXPLORATORY OBJECTIVES: I. To collect blood and tissue specimens for future translational science studies. II. To assess post-induction plasma EBV DNA (detectable \[\>= 1 copies/mL\] vs. undetectable \[0 copies/mL\]) as a predictive biomarker. OUTLINE: INDUCTION THERAPY: Patients receive nivolumab intravenously (IV) over 30 minutes on day 1 of each cycle, cisplatin IV or carboplatin IV over 30-60 minutes on day 1 of each cycle and gemcitabine IV over 30 minutes on days 1 and 8 of each cycle. Cycles repeat every 21 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT) or magnetic resonance imaging (MRI) and blood sample collection during screening and on study. MAINTENANCE THERAPY: Patients who do not progress radiologically are randomized to 1 of 2 arms. ARM I: Patients receive nivolumab IV over 30 minutes. Cycles repeat every 4 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo CT or MRI on study. Patients also undergo positron emission tomography (PET)/CT or bone scan as clinically indicated. ARM II: Patients receive nivolumab IV over 30 minutes and relatlimab IV over 30-90 minutes. Cycles repeat every 4 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients undergo CT or MRI on study. Patients also undergo PET/CT or bone scan as clinically indicated. After completion of study treatment, patients are followed up every 4 months for 2 years, every 6 months in years 3-5, and then annually.

Eligibility Criteria

Age Range: 18 years to No maximum

Inclusion Criteria: * PRIOR TO STEP 1 REGISTRATION: * Pathologically (histologically or cytologically) proven diagnosis of nasopharyngeal carcinoma (NPC) that has recurred locoregionally and/or is present at distant sites. Patients who present with metastatic disease (de novo) at diagnosis are also eligible. For locoregional recurrence, the disease must not be amenable to potentially curative surgery or re-irradiation. Eligible patient must have the following characteristics: * Tumor showing (histological/cytological) Epstein-Barr encoded ribonucleic acid (EBER)-positivity (e.g., In situ hybridization, immunohistochemistry) or * A known history of detectable plasma EBV DNA (via a polymerase chain reaction \[PCR\]-based assay) at any time point since the initial diagnosis of NPC. * Measurable disease as defined by RECIST 1.1 criteria. Lesion(s) that have been irradiated previously can be counted as measurable as long as radiological progression after the prior radiation therapy has been demonstrated. * Contrast enhanced CT scan of the chest. The contrast enhanced CT component of a whole-body PET-CT is also acceptable. The plain (non-contrast) CT component of a PET-CT is not acceptable. * CT the abdomen and pelvis, if clinically indicated (diagnostic quality with contrast, unless contraindicated). * Patients with known locoregional disease must have contrast enhanced MRI or CT of the nasopharynx and neck as this disease site(s) may be assessed as target lesions. For patients without known locoregional disease, imaging of the nasopharynx and neck is optional. * Symptomatic and active brain metastases and/or leptomeningeal metastasis on CT and/or MRI imaging: Patients who have prior therapies for brain and leptomeningeal metastasis or cord/cauda compression who are clinically stable for \>= 2 months prior to registration and have discontinued systemic steroids therapy (\> 10 mg/day prednisone or equivalent) \> 4 weeks prior to registration are eligible. * Patients with base of skull involvement by NPC are allowed unless their disease is directly invading the brain parenchyma, associated with clinical symptoms and/or significant vasogenic edema on radiological imaging. * Age \>= 18 years. * Eastern Cooperative Oncology Group (ECOG) (Zubrod) performance status of 0-2. * Negative urine or serum pregnancy test (in persons of childbearing potential) within 14 days prior to registration. Childbearing potential is defined as any person who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal. * Absolute neutrophil count (ANC) \>= 1500 cells/mm\^3. * Platelets \>= 100,000 cells/mm\^3. * Hemoglobin (Hgb) \>= 8.0 g/dL (Transfusion is accepted. Erythropoietin dependency not accepted.). * Total bilirubin =\< 1.5 × institutional upper limit of normal (ULN) or direct bilirubin =\< ULN for patients with total bilirubin levels \> 1.5 × ULN. Patients with known Gilbert's disease who have serum bilirubin level =\< 3 × ULN may be enrolled. * Alanine transaminase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) =\< 3 × ULN (=\< 5 × ULN for patients with liver metastases). * Serum creatinine =\< 1.5 × ULN or calculated creatinine clearance (CrCl) based on Cockcroft-Gault equation \>= 30 mL/min for patients with serum creatinine levels \> 1.5 × ULN. Cisplatin or carboplatin may be used at the discretion of the investigator - except for patients with CrCl between 30-50 mL/min, for whom carboplatin should be used instead of cisplatin. CrCl must be \> 50 mL/min for cisplatin to be used. * Albumin-adjusted calcium level based on corrected calcium equation =\< 1.5 × ULN (patients are allowed to have treatment for hypercalcemia prior to starting treatment). * No prior systemic treatment of palliative intent for recurrent/metastatic (R/M) NPC including cytotoxic chemotherapy. Prior treatment for non-recurrent and non-metastatic NPC is allowed. Systemic therapy given prior to curative intent re-irradiation or surgery is allowed for potentially curable locoregional recurrence. * No prior treatment with a PD-1 inhibitor (except if given as adjuvant or neoadjuvant therapy for NPC), PD-L1 inhibitor, anti-PD-L2 inhibitor, LAG-3 inhibitor, CTLA-4 inhibitor (except if given as adjuvant or neoadjuvant therapy for non-recurrent and non-metastatic NPC), or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways. * The interval between the last dose of curative-intent treatment for non-recurrent, non-metastatic NPC, including definitive radiotherapy (RT) and/or induction, concurrent, or adjuvant chemotherapy and recurrence must be ˃ 6 months. * Clinically significant toxicities from any prior systemic therapy or radiotherapy must have resolved to grade 0 or 1 as per National Cancer Institute (NCI) CTCAE v 5.0 - except alopecia, dry mouth, dysgeusia, dysphagia, and fatigue. Patients with a history of grade 3-4 cisplatin related neuropathy must have recovered to grade 0-2 prior to registration. Patients with a history of hearing impairment, or ototoxicity from prior cisplatin, of any grade are allowed. * No prior palliative RT within 30 days prior to registration unless the irradiated site(s) are not the target lesions. The irradiated site(s) also must not be the only sites of measurable recurrent disease. * No major surgical procedures within 30 days prior to registration. * No history of unstable angina requiring hospitalization within the last 6 months. * No history of myocardial infarction within the last 6 months. * New York Heart Association Functional Classification II or better (New York Heart Association \[NYHA\] Functional Classification III/IV are not eligible). Patients with symptomatic coronary artery disease, congestive heart failure or a known history of having a left ventricular ejection fraction \< 50% must be stably controlled with medication in the opinion of the treating physician, in consultation with a cardiologist if appropriate. * No prior history of myocarditis. * No active infection requiring IV antibiotics, IV antiviral, or IV antifungal treatments at the time of study registration. * No history of (non-infectious) pneumonitis that required steroids or current pneumonitis requiring steroids and/or immunosuppressive therapy, idiopathic pulmonary fibrosis, drug-induced pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans), or idiopathic pneumonitis. * No history of multi-drug resistant mycobacterium tuberculosis (TB) or active TB, as defined by systemic treatment received =\< 2 years prior to registration. Note: Patients who had a history of treated TB ˃ 2 years prior to registration are allowed. * No prior solid organ transplant or bone marrow transplant. * No conditions requiring systemic treatment with either immunosuppressive doses of corticosteroids (\> 10 mg daily prednisone or equivalents) or other immunosuppressive medications within 14 days of registration. Inhaled or topical steroids and adrenal replacement doses \< 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. Steroid premedication for the prophylaxis of CT contrast-related allergies is allowed. The use of dexamethasone as an anti-emetic premedication prior to chemotherapy is also allowed. * No active autoimmune disease requiring systemic treatment (i.e., disease modifying agents, corticosteroids, or immunosuppressive drugs) within the past 2 years. These may include (but not limited to) patients with a history of immune-related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE), rheumatoid arthritis, connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's disease, ulcerative colitis, autoimmune hepatitis, glomerulonephritis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome. * Note: Patients are permitted to enroll if they have vitiligo; type I diabetes mellitus; hypothyroidism, pituitary or adrenal insufficiency requiring only hormone replacement; alopecia; and/or psoriasis not requiring systemic treatment. Conditions not expected to recur in the absence of an external trigger are permitted to enroll. * No prior live vaccine within 30 days prior to registration. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster, yellow fever, rabies, Bacillus Calmette-Guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist \[registered trademark\]) are live attenuated vaccines and are not allowed. Coronavirus disease 2019 (COVID-19) vaccines that are approved by the local drug regulatory authority of the participating region are allowed. * No known history of grade 3-4 allergic reaction or hypersensitivity reaction to cisplatin, carboplatin, or gemcitabine. * No known history of grade 4 hypersensitivity (or infusion) reaction to any monoclonal antibody. Patients who had prior grade 3 hypersensitivity (or infusion) reaction but could tolerate resumption of the antibody treatment after appropriate pre-medication are eligible. * PRIOR TO STEP 2 REGISTRATION: * Collection of plasma EBV DNA at baseline is mandatory for all patients prior to Step 2 registration and induction treatment. * Note: Submission of the baseline sample will be batch shipped. * PRIOR TO STEP 3 REGISTRATION/RANDOMIZATION: PATIENTS WITHOUT PROGRESSIVE DISEASE (PD) ONLY: * All patients must have received minimum of 3 cycles, and up to a maximum of 6 cycles of induction treatment within 20 weeks from cycle 1, day 1 of induction treatment (i.e., patients must have completed all induction treatment within 20 weeks from cycle 1 day 1, including the treatment breaks). Patients must have completed 6 cycles of induction treatment, except in the following circumstances: * Significant dose delays as a result of treatment-related toxicities. * Intercurrent illness(s), that rendered the patient unable to continue induction treatment. * Note: If a patient received \< 6 cycles of induction treatment for reasons other than the above circumstances, they will not be eligible for randomization. * A CT scan within 30 days prior to Step 3 registration/randomization is required. If the most recent scan performed is not within this time frame, a repeat scan is required to assess response. * Did not meet any criteria that result in permanent discontinuation of study treatment during induction treatment phase. * Must meet the criteria for starting/resuming a new cycle of maintenance treatment. * Did not experience any nivolumab-related autoimmune toxicities that would result in permanent discontinuation of nivolumab during the induction treatment phase. * Collection of the plasma EBV DNA post-induction treatment is mandatory. * Note: Submission of the post-induction sample will be batch shipped.

Interventions

PROCEDURE

Biospecimen Collection

PROCEDURE

Bone Scan

DRUG

Carboplatin

DRUG

Cisplatin

PROCEDURE

Computed Tomography

DRUG

Gemcitabine

PROCEDURE

Magnetic Resonance Imaging

BIOLOGICAL

Nivolumab

PROCEDURE

Positron Emission Tomography

BIOLOGICAL

Relatlimab

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Conditions

Metastatic Nasopharyngeal CarcinomaRecurrent Nasopharyngeal CarcinomaStage IV Nasopharyngeal Carcinoma AJCC v8

Locations

Kaiser Permanente Dublin

Dublin, California 94568

United States

Kaiser Permanente-Fremont

Fremont, California 94538

United States

Kaiser Permanente Fresno Orchard Plaza

Fresno, California 93720

United States

Kaiser Permanente-Fresno

Fresno, California 93720

United States

Keck Medicine of USC Koreatown

Los Angeles, California 90020

United States

Los Angeles General Medical Center

Los Angeles, California 90033

United States

USC / Norris Comprehensive Cancer Center

Los Angeles, California 90033

United States

Kaiser Permanente- Modesto MOB II

Modesto, California 95356

United States

Kaiser Permanente-Modesto

Modesto, California 95356

United States

USC Norris Oncology/Hematology-Newport Beach

Newport Beach, California 92663

United States

Kaiser Permanente-Oakland

Oakland, California 94611

United States

Stanford Cancer Institute Palo Alto

Palo Alto, California 94304

United States

Kaiser Permanente-Roseville

Roseville, California 95661

United States

Kaiser Permanente Downtown Commons

Sacramento, California 95814

United States

University of California Davis Comprehensive Cancer Center

Sacramento, California 95817

United States

Kaiser Permanente-South Sacramento

Sacramento, California 95823

United States

Kaiser Permanente-San Francisco

San Francisco, California 94115

United States

Kaiser Permanente-Santa Teresa-San Jose

San Jose, California 95119

United States

Kaiser Permanente San Leandro

San Leandro, California 94577

United States

Kaiser San Rafael-Gallinas

San Rafael, California 94903

United States

Kaiser Permanente Medical Center - Santa Clara

Santa Clara, California 95051

United States

Kaiser Permanente-Santa Rosa

Santa Rosa, California 95403

United States

Kaiser Permanente-South San Francisco

South San Francisco, California 94080

United States

Kaiser Permanente-Vallejo

Vallejo, California 94589

United States

Kaiser Permanente-Walnut Creek

Walnut Creek, California 94596

United States

Emory University Hospital Midtown

Atlanta, Georgia 30308

United States

Kaiser Permanente Moanalua Medical Center

Honolulu, Hawaii 96819

United States

Saint Alphonsus Cancer Care Center-Boise

Boise, Idaho 83706

United States

Saint Alphonsus Cancer Care Center-Caldwell

Caldwell, Idaho 83605

United States

Kootenai Health - Coeur d'Alene

Coeur d'Alene, Idaho 83814

United States

Saint Alphonsus Cancer Care Center-Nampa

Nampa, Idaho 83687

United States

Kootenai Clinic Cancer Services - Post Falls

Post Falls, Idaho 83854

United States

Kootenai Clinic Cancer Services - Sandpoint

Sandpoint, Idaho 83864

United States

Northwestern University

Chicago, Illinois 60611

United States

University of Illinois

Chicago, Illinois 60612

United States

Carle at The Riverfront

Danville, Illinois 61832

United States

Northwestern Medicine Cancer Center Kishwaukee

DeKalb, Illinois 60115

United States

Carle Physician Group-Effingham

Effingham, Illinois 62401

United States

Northwestern Medicine Cancer Center Delnor

Geneva, Illinois 60134

United States

Northwestern Medicine Glenview Outpatient Center

Glenview, Illinois 60026

United States

Northwestern Medicine Grayslake Outpatient Center

Grayslake, Illinois 60030

United States

Northwestern Medicine Lake Forest Hospital

Lake Forest, Illinois 60045

United States

Carle Physician Group-Mattoon/Charleston

Mattoon, Illinois 61938

United States

Northwestern Medicine Orland Park

Orland Park, Illinois 60462

United States

Carle Cancer Center

Urbana, Illinois 61801

United States

Northwestern Medicine Cancer Center Warrenville

Warrenville, Illinois 60555

United States

UI Health Care Mission Cancer and Blood - Ankeny Clinic

Ankeny, Iowa 50023

United States

Saint Anthony Regional Hospital

Carroll, Iowa 51401

United States

UI Health Care Mission Cancer and Blood - West Des Moines Clinic

Clive, Iowa 50325

United States

Heartland Oncology and Hematology LLP

Council Bluffs, Iowa 51503

United States

Methodist Jennie Edmundson Hospital

Council Bluffs, Iowa 51503

United States

Nebraska Cancer Specialists/Oncology Hematology West PC - MEJ

Council Bluffs, Iowa 51503

United States

Iowa Methodist Medical Center

Des Moines, Iowa 50309

United States

UI Health Care Mission Cancer and Blood - Des Moines Clinic

Des Moines, Iowa 50309

United States

Broadlawns Medical Center

Des Moines, Iowa 50314

United States

Mercy Medical Center - Des Moines

Des Moines, Iowa 50314

United States

UI Health Care Mission Cancer and Blood - Laurel Clinic

Des Moines, Iowa 50314

United States

UI Healthcare Mission Cancer and Blood - Fort Dodge

Fort Dodge, Iowa 50501

United States

UI Health Care Mission Cancer and Blood - Waukee Clinic

Waukee, Iowa 50263

United States

Mercy Hospital South

St Louis, Missouri 63128

United States

Mercy Hospital Saint Louis

St Louis, Missouri 63141

United States

Community Hospital of Anaconda

Anaconda, Montana 59711

United States

Billings Clinic Cancer Center

Billings, Montana 59101

United States

Bozeman Health Deaconess Hospital

Bozeman, Montana 59715

United States

Benefis Sletten Cancer Institute

Great Falls, Montana 59405

United States

Logan Health Medical Center

Kalispell, Montana 59901

United States

Community Medical Center

Missoula, Montana 59804

United States

Nebraska Cancer Specialists/Oncology Hematology West PC - MECC

Omaha, Nebraska 68114

United States

Nebraska Methodist Hospital

Omaha, Nebraska 68114

United States

Oncology Associates PC

Omaha, Nebraska 68114

United States

University of Cincinnati Cancer Center-UC Medical Center

Cincinnati, Ohio 45219

United States

University of Cincinnati Cancer Center-West Chester

West Chester, Ohio 45069

United States

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma 73104

United States

Oklahoma Cancer Specialists and Research Institute-Tulsa

Tulsa, Oklahoma 74146

United States

Saint Alphonsus Cancer Care Center-Ontario

Ontario, Oregon 97914

United States

Providence Portland Medical Center

Portland, Oregon 97213

United States

Providence Saint Vincent Medical Center

Portland, Oregon 97225

United States

Medical University of South Carolina

Charleston, South Carolina 29425

United States

Swedish Medical Center-First Hill

Seattle, Washington 98122

United States

ProHealth D N Greenwald Center

Mukwonago, Wisconsin 53149

United States

ProHealth Oconomowoc Memorial Hospital

Oconomowoc, Wisconsin 53066

United States

ProHealth Waukesha Memorial Hospital

Waukesha, Wisconsin 53188

United States

UW Cancer Center at ProHealth Care

Waukesha, Wisconsin 53188

United States

Peter MacCallum Cancer Centre

Melbourne, Victoria 3000

Australia

University Health Network-Princess Margaret Hospital

Toronto, Ontario M5G 2M9

Canada

Chinese University of Hong Kong-Prince of Wales Hospital

Shatin,

Hong Kong

National University Hospital Singapore

Singapore, 119074

Singapore

National Cancer Centre Singapore

Singapore, 168583

Singapore