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

NCT06029270 | Recruiting Phase 2 FDA Drug

• 3 other identifiers: NCI-2023-06678NRG-HN011U10CA180868
• Study Type: interventional
• Target: 156
• Locations: 5 countries
• Sites: 88

Brief 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.

Conditions

Stage IV Nasopharyngeal Carcinoma AJCC v8; Recurrent Nasopharyngeal Carcinoma; Metastatic Nasopharyngeal Carcinoma

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS)

  Will be assessed in both treatment arms and will be estimated using the Kaplan-Meier method. The comparison of PFS distributions between treatment arms will be performed using the log-rank test. Additional analyses of treatment effect will be performed using Cox models with the stratification factors included as a fixed covariates, as well as other tumor and patient characteristics, listed below. Median PFS and the corresponding 95% confidence intervals (CIs) for each arm will be estimated with the Brookmeyer-Crowley method. Multivariable analysis will be performed using a Cox proportional hazards model and relevant patient and tumor characteristics (country \[Asian sites versus (vs.) Non-Asian sites\], keratinizing squamous carcinoma, sex, age, and baseline Epstein-Barr virus (EBV) deoxyribonucleic acid \[DNA\]). Hazard ratios and their respective 85% lower confidence bound, and 95% confidence intervals will be provided.

  Time from randomization to progressive disease (PD) or death due to any cause, assessed up to 6 years

Secondary Outcomes (8)

• Overall survival (OS)

  Time from randomization to death due to any cause, assessed up to 6 years

• Tumor response

  Up to 6 years

• Locoregional failure

  Up to 6 years

• Distant metastasis

  Up to 6 years

• Incidence of adverse events (AEs)

  Up to 6 years

Other Outcomes (1)

• Post-induction EBV DNA as a predictive biomarker

  Up to 6 years

Study Arms (3)

Arm I (Nivolumab)

ACTIVE COMPARATOR

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 PET/CT or bone scan as clinically indicated.

Procedure: Bone Scan; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Biological: Nivolumab; Procedure: Positron Emission Tomography

Arm II (Nivolumab, relatlimab)

EXPERIMENTAL

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.

Procedure: Bone Scan; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Biological: Nivolumab; Procedure: Positron Emission Tomography; Biological: Relatlimab

Induction therapy (Platinum-gemcitabine-nivolumab)

EXPERIMENTAL

Patients receive nivolumab 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 CT or MRI and blood sample collection during screening and on study.

Procedure: Biospecimen Collection; Drug: Carboplatin; Drug: Cisplatin; Procedure: Computed Tomography; Drug: Gemcitabine; Procedure: Magnetic Resonance Imaging; Biological: Nivolumab

Interventions

Carboplatin DRUG

Given IV

Also known as: Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carboplatinum, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, JM8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, Ribocarbo

Induction therapy (Platinum-gemcitabine-nivolumab)

Cisplatin DRUG

Given IV

Also known as: Abiplatin, Blastolem, Briplatin, CDDP, Cis-diammine-dichloroplatinum, Cis-diamminedichloridoplatinum, Cis-diamminedichloro Platinum (II), Cis-diamminedichloroplatinum, Cis-dichloroammine Platinum (II), Cis-platinous Diamine Dichloride, Cis-platinum, Cis-platinum II, Cis-platinum II Diamine Dichloride, Cismaplat, Cisplatina, Cisplatinum, Cisplatyl, Citoplatino, Citosin, Cysplatyna, DDP, Lederplatin, Metaplatin, Neoplatin, Peyrone's Chloride, Peyrone's Salt, Placis, Plastistil, Platamine, Platiblastin, Platiblastin-S, Platinex, Platinol, Platinol- AQ, Platinol-AQ, Platinol-AQ VHA Plus, Platinoxan, Platinum, Platinum Diamminodichloride, Platiran, Platistin, Platosin

Induction therapy (Platinum-gemcitabine-nivolumab)

Bone Scan PROCEDURE

Undergo bone scan

Also known as: Bone Scintigraphy

Arm I (Nivolumab); Arm II (Nivolumab, relatlimab)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

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

Induction therapy (Platinum-gemcitabine-nivolumab)

Computed Tomography PROCEDURE

Undergo CT or PET/CT

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, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Arm I (Nivolumab); Arm II (Nivolumab, relatlimab); Induction therapy (Platinum-gemcitabine-nivolumab)

Gemcitabine DRUG

Given IV

Also known as: dFdC, dFdCyd, Difluorodeoxycytidine

Induction therapy (Platinum-gemcitabine-nivolumab)

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

Arm I (Nivolumab); Arm II (Nivolumab, relatlimab); Induction therapy (Platinum-gemcitabine-nivolumab)

Nivolumab BIOLOGICAL

Given IV

Also known as: ABP 206, BCD-263, BMS 936558, BMS-936558, BMS936558, CMAB819, MDX 1106, MDX-1106, MDX1106, NIVO, Nivolumab Biosimilar ABP 206, Nivolumab Biosimilar BCD-263, Nivolumab Biosimilar CMAB819, ONO 4538, ONO-4538, ONO4538, Opdivo

Arm I (Nivolumab); Arm II (Nivolumab, relatlimab); Induction therapy (Platinum-gemcitabine-nivolumab)

Positron Emission Tomography PROCEDURE

Undergo PET/CT

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, PT

Arm I (Nivolumab); Arm II (Nivolumab, relatlimab)

Relatlimab BIOLOGICAL

Given IV

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

Arm II (Nivolumab, relatlimab)

Eligibility Criteria

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

You may qualify if:

• 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.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (88)

Kaiser Permanente Dublin

Dublin, California, 94568, United States

RECRUITING

Kaiser Permanente-Fremont

Fremont, California, 94538, United States

RECRUITING

Kaiser Permanente Fresno Orchard Plaza

Fresno, California, 93720, United States

RECRUITING

Kaiser Permanente-Fresno

Fresno, California, 93720, United States

RECRUITING

Keck Medicine of USC Koreatown

Los Angeles, California, 90020, United States

RECRUITING

Los Angeles General Medical Center

Los Angeles, California, 90033, United States

RECRUITING

USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

RECRUITING

Kaiser Permanente- Modesto MOB II

Modesto, California, 95356, United States

RECRUITING

Kaiser Permanente-Modesto

Modesto, California, 95356, United States

RECRUITING

USC Norris Oncology/Hematology-Newport Beach

Newport Beach, California, 92663, United States

RECRUITING

Kaiser Permanente-Oakland

Oakland, California, 94611, United States

RECRUITING

Stanford Cancer Institute Palo Alto

Palo Alto, California, 94304, United States

RECRUITING

Kaiser Permanente-Roseville

Roseville, California, 95661, United States

RECRUITING

Kaiser Permanente Downtown Commons

Sacramento, California, 95814, United States

RECRUITING

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

RECRUITING

Kaiser Permanente-South Sacramento

Sacramento, California, 95823, United States

RECRUITING

Kaiser Permanente-San Francisco

San Francisco, California, 94115, United States

RECRUITING

Kaiser Permanente-Santa Teresa-San Jose

San Jose, California, 95119, United States

RECRUITING

Kaiser Permanente San Leandro

San Leandro, California, 94577, United States

RECRUITING

Kaiser San Rafael-Gallinas

San Rafael, California, 94903, United States

RECRUITING

Kaiser Permanente Medical Center - Santa Clara

Santa Clara, California, 95051, United States

RECRUITING

Kaiser Permanente-Santa Rosa

Santa Rosa, California, 95403, United States

RECRUITING

Kaiser Permanente-South San Francisco

South San Francisco, California, 94080, United States

RECRUITING

Kaiser Permanente-Vallejo

Vallejo, California, 94589, United States

RECRUITING

Kaiser Permanente-Walnut Creek

Walnut Creek, California, 94596, United States

RECRUITING

Emory University Hospital Midtown

Atlanta, Georgia, 30308, United States

RECRUITING

Kaiser Permanente Moanalua Medical Center

Honolulu, Hawaii, 96819, United States

RECRUITING

Saint Alphonsus Cancer Care Center-Boise

Boise, Idaho, 83706, United States

SUSPENDED

Saint Alphonsus Cancer Care Center-Caldwell

Caldwell, Idaho, 83605, United States

SUSPENDED

Kootenai Health - Coeur d'Alene

Coeur d'Alene, Idaho, 83814, United States

RECRUITING

Saint Alphonsus Cancer Care Center-Nampa

Nampa, Idaho, 83687, United States

SUSPENDED

Kootenai Clinic Cancer Services - Post Falls

Post Falls, Idaho, 83854, United States

RECRUITING

Kootenai Clinic Cancer Services - Sandpoint

Sandpoint, Idaho, 83864, United States

RECRUITING

Northwestern University

Chicago, Illinois, 60611, United States

RECRUITING

University of Illinois

Chicago, Illinois, 60612, United States

RECRUITING

Carle at The Riverfront

Danville, Illinois, 61832, United States

RECRUITING

Northwestern Medicine Cancer Center Kishwaukee

DeKalb, Illinois, 60115, United States

RECRUITING

Carle Physician Group-Effingham

Effingham, Illinois, 62401, United States

RECRUITING

Northwestern Medicine Cancer Center Delnor

Geneva, Illinois, 60134, United States

RECRUITING

Northwestern Medicine Glenview Outpatient Center

Glenview, Illinois, 60026, United States

RECRUITING

Northwestern Medicine Grayslake Outpatient Center

Grayslake, Illinois, 60030, United States

RECRUITING

Northwestern Medicine Lake Forest Hospital

Lake Forest, Illinois, 60045, United States

RECRUITING

Carle Physician Group-Mattoon/Charleston

Mattoon, Illinois, 61938, United States

RECRUITING

Northwestern Medicine Orland Park

Orland Park, Illinois, 60462, United States

RECRUITING

Carle Cancer Center

Urbana, Illinois, 61801, United States

RECRUITING

Northwestern Medicine Cancer Center Warrenville

Warrenville, Illinois, 60555, United States

RECRUITING

UI Health Care Mission Cancer and Blood - Ankeny Clinic

Ankeny, Iowa, 50023, United States

RECRUITING

Saint Anthony Regional Hospital

Carroll, Iowa, 51401, United States

RECRUITING

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

Clive, Iowa, 50325, United States

RECRUITING

Heartland Oncology and Hematology LLP

Council Bluffs, Iowa, 51503, United States

SUSPENDED

Methodist Jennie Edmundson Hospital

Council Bluffs, Iowa, 51503, United States

RECRUITING

Nebraska Cancer Specialists/Oncology Hematology West PC - MEJ

Council Bluffs, Iowa, 51503, United States

RECRUITING

Iowa Methodist Medical Center

Des Moines, Iowa, 50309, United States

RECRUITING

UI Health Care Mission Cancer and Blood - Des Moines Clinic

Des Moines, Iowa, 50309, United States

RECRUITING

Broadlawns Medical Center

Des Moines, Iowa, 50314, United States

RECRUITING

Mercy Medical Center - Des Moines

Des Moines, Iowa, 50314, United States

RECRUITING

UI Health Care Mission Cancer and Blood - Laurel Clinic

Des Moines, Iowa, 50314, United States

RECRUITING

UI Healthcare Mission Cancer and Blood - Fort Dodge

Fort Dodge, Iowa, 50501, United States

RECRUITING

UI Health Care Mission Cancer and Blood - Waukee Clinic

Waukee, Iowa, 50263, United States

RECRUITING

Mercy Hospital South

St Louis, Missouri, 63128, United States

RECRUITING

Mercy Hospital Saint Louis

St Louis, Missouri, 63141, United States

RECRUITING

Community Hospital of Anaconda

Anaconda, Montana, 59711, United States

RECRUITING

Billings Clinic Cancer Center

Billings, Montana, 59101, United States

RECRUITING

Bozeman Health Deaconess Hospital

Bozeman, Montana, 59715, United States

RECRUITING

Benefis Sletten Cancer Institute

Great Falls, Montana, 59405, United States

RECRUITING

Logan Health Medical Center

Kalispell, Montana, 59901, United States

RECRUITING

Community Medical Center

Missoula, Montana, 59804, United States

RECRUITING

Nebraska Cancer Specialists/Oncology Hematology West PC - MECC

Omaha, Nebraska, 68114, United States

RECRUITING

Nebraska Methodist Hospital

Omaha, Nebraska, 68114, United States

RECRUITING

Oncology Associates PC

Omaha, Nebraska, 68114, United States

SUSPENDED

University of Cincinnati Cancer Center-UC Medical Center

Cincinnati, Ohio, 45219, United States

ACTIVE NOT RECRUITING

University of Cincinnati Cancer Center-West Chester

West Chester, Ohio, 45069, United States

ACTIVE NOT RECRUITING

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

RECRUITING

Oklahoma Cancer Specialists and Research Institute-Tulsa

Tulsa, Oklahoma, 74146, United States

SUSPENDED

Saint Alphonsus Cancer Care Center-Ontario

Ontario, Oregon, 97914, United States

SUSPENDED

Providence Portland Medical Center

Portland, Oregon, 97213, United States

RECRUITING

Providence Saint Vincent Medical Center

Portland, Oregon, 97225, United States

RECRUITING

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

RECRUITING

Swedish Medical Center-First Hill

Seattle, Washington, 98122, United States

RECRUITING

ProHealth D N Greenwald Center

Mukwonago, Wisconsin, 53149, United States

RECRUITING

ProHealth Oconomowoc Memorial Hospital

Oconomowoc, Wisconsin, 53066, United States

RECRUITING

ProHealth Waukesha Memorial Hospital

Waukesha, Wisconsin, 53188, United States

RECRUITING

UW Cancer Center at ProHealth Care

Waukesha, Wisconsin, 53188, United States

RECRUITING

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

SUSPENDED

University Health Network-Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

RECRUITING

Chinese University of Hong Kong-Prince of Wales Hospital

Shatin, Hong Kong

SUSPENDED

National University Hospital Singapore

Singapore, 119074, Singapore

SUSPENDED

National Cancer Centre Singapore

Singapore, 168583, Singapore

SUSPENDED

MeSH Terms

Conditions

Nasopharyngeal Carcinoma

Interventions

Specimen Handling; Carboplatin; Cisplatin; 1,2-diaminocyclohexaneplatinum II citrate; Platinum; Gemcitabine; Magnetic Resonance Spectroscopy; Nivolumab; relatlimab; Immunoglobulin G; Disulfides

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Nasopharyngeal Neoplasms; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Coordination Complexes; Organic Chemicals; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Metals, Heavy; Elements; Transition Elements; Metals; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; 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; Hydrogen Sulfide; Sulfur Compounds

Study Officials

• Brigette B Ma

  NRG Oncology

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: September 7, 2023
• First Posted: September 8, 2023
• Study Start: July 15, 2024
• Primary Completion (Estimated): April 30, 2029
• Study Completion (Estimated): April 30, 2029
• Last Updated: June 11, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

CA (1); US (83); SG (2); AU (1); HK (1)