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

PHASE2RECRUITING

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.

Study details:

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

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

Inclusion criteria

  1. Pathologically (histologically or cytologically) proven diagnosis of nasopharyngeal carcinoma (NPC) that has recurred locoregionally and/or is present at distant sites.
  2. 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.
  3. Measurable disease as defined by RECIST 1.1 criteria.
  4. Age >= 18 years.
  5. Eastern Cooperative Oncology Group (ECOG) (Zubrod) performance status of 0-2.
  6. Negative urine or serum pregnancy test (in persons of childbearing potential) within 14 days prior to registration.
  7. Absolute neutrophil count (ANC) >= 1500 cells/mm^3.
  8. Platelets >= 100,000 cells/mm^3.
  9. Hemoglobin (Hgb) >= 8.0 g/dL.
  10. Total bilirubin =< 1.5 × institutional upper limit of normal (ULN) or direct bilirubin =< ULN for patients with total bilirubin levels > 1.5 × ULN.
  11. Alanine transaminase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 3 × ULN (=< 5 × ULN for patients with liver metastases).
  12. Serum creatinine =< 1.5 × ULN or calculated creatinine clearance (CrCl) based on Cockcroft-Gault equation >= 30 mL/min.
  13. Albumin-adjusted calcium level based on corrected calcium equation =< 1.5 × ULN.
  14. No prior systemic treatment for recurrent/metastatic (R/M) NPC including cytotoxic chemotherapy.
  15. 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.
  16. The interval between the last dose of curative-intent treatment for non-recurrent, non-metastatic NPC must be > 6 months.
  17. 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.
  18. No prior palliative RT within 30 days prior to registration.
  19. No major surgical procedures within 30 days prior to registration.
  20. No history of unstable angina requiring hospitalization within the last 6 months.
  21. No history of myocardial infarction within the last 6 months.
  22. New York Heart Association Functional Classification II or better.
  23. No prior history of myocarditis.
  24. No active infection requiring IV antibiotics, IV antiviral, or IV antifungal treatments at the time of study registration.
  25. No history of (non-infectious) pneumonitis that required steroids or current pneumonitis requiring steroids and/or immunosuppressive therapy.
  26. No history of multi-drug resistant mycobacterium tuberculosis (TB) or active TB, as defined by systemic treatment received =< 2 years prior to registration.
  27. No prior solid organ transplant or bone marrow transplant.
  28. 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.
  29. No active autoimmune disease requiring systemic treatment (i.e., disease modifying agents, corticosteroids, or immunosuppressive drugs) within the past 2 years.
  30. No prior live vaccine within 30 days prior to registration.
  31. No known history of grade 3-4 allergic reaction or hypersensitivity reaction to cisplatin, carboplatin, or gemcitabine.
  32. No known history of grade 4 hypersensitivity (or infusion) reaction to any monoclonal antibody.

Exclusion criteria

  1. No prior systemic treatment for recurrent/metastatic (R/M) NPC including cytotoxic chemotherapy.
  2. 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.
  3. No prior palliative RT within 30 days prior to registration.
  4. No major surgical procedures within 30 days prior to registration.
  5. No history of unstable angina requiring hospitalization within the last 6 months.
  6. No history of myocardial infarction within the last 6 months.
  7. No prior history of myocarditis.
  8. No active infection requiring IV antibiotics, IV antiviral, or IV antifungal treatments at the time of study registration.
  9. No history of (non-infectious) pneumonitis that required steroids or current pneumonitis requiring steroids and/or immunosuppressive therapy.
  10. No history of multi-drug resistant mycobacterium tuberculosis (TB) or active TB, as defined by systemic treatment received =< 2 years prior to registration.
  11. No prior solid organ transplant or bone marrow transplant.
  12. 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.
  13. No active autoimmune disease requiring systemic treatment (i.e., disease modifying agents, corticosteroids, or immunosuppressive drugs) within the past 2 years.
  14. No prior live vaccine within 30 days prior to registration.
  15. No known history of grade 3-4 allergic reaction or hypersensitivity reaction to cisplatin, carboplatin, or gemcitabine.
  16. No known history of grade 4 hypersensitivity (or infusion) reaction to any monoclonal antibody.

Eligibility

Age eligible for study : NA

Healthy volunteers accepted : No

Gender eligible for study: ALL

Things to know

Study dates

Study start:

Primary completion:

Study completion finish:

study type

Study type

TREATMENT

phase

Phase

    PHASE2

trial

Study ID

NCT06029270

Intervention or treatment

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

Conditions

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

  • Condition: Metastatic Nasopharyngeal Carcinoma, Recurrent Nasopharyngeal Carcinoma and more

  • PROCEDURE: Biospecimen Collection and other drugs

  • Melbourne, Victoria, Australia

  • Sponsor: National Cancer Institute (NCI)

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Research sites nearby

Closest Location:

Peter MacCallum Cancer Centre

Select from list below to view details:

  • Peter MacCallum Cancer Centre

    Melbourne, Victoria, Australia

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Who is running the clinical trial?

NCI(

National Cancer Institute (NCI)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Participant Group/ArmIntervention/Treatment
ACTIVE_COMPARATOR: Arm I (Nivolumab)
  • 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
    EXPERIMENTAL: Arm II (Nivolumab, relatlimab)
    • 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
      EXPERIMENTAL: Induction therapy (Platinum-gemcitabine-nivolumab)
      • 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

        What is the study measuring?

        Primary Outcome

        MeasureDescriptionTime Frame
        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 Outcome

        MeasureDescriptionTime Frame
        Overall survival (OS)Will be estimated using the Kaplan-Meier method and between-arm differences will be assessed using the log-rank test. Median OS and the corresponding 95% CIs using log-log transformation to survival function for each arm will be estimated with the Brookmeyer-Crowley method.Time from randomization to death due to any cause, assessed up to 6 years
        Tumor responseWill be assessed using Response Evaluation Criteria in Solid Tumors version 1.1. Cox proportional hazards models will be used to determine hazard ratios (cause-specific hazard ratios in the case of endpoints with competing risks) and to assess the effects of covariates of interest. Fine-Gray sub-distribution hazards Cox model will be used to complement the competing risk analyses.Up to 6 years
        Locoregional failureCox proportional hazards models will be used to determine hazard ratios (cause-specific hazard ratios in the case of endpoints with competing risks) and to assess the effects of covariates of interest. Fine-Gray sub-distribution hazards Cox model will be used to complement the competing risk analyses.Up to 6 years
        Distant metastasisCox proportional hazards models will be used to determine hazard ratios (cause-specific hazard ratios in the case of endpoints with competing risks) and to assess the effects of covariates of interest. Fine-Gray sub-distribution hazards Cox model will be used to complement the competing risk analyses.Up to 6 years
        Incidence of adverse events (AEs)Will be graded using Common Terminology Criteria for Adverse Events version 5.0. Counts of all AEs by grade will be provided by treatment arm. Counts and frequencies will be provided for the worst grade AE experienced by the patient by treatment arm. The rate of patients with at least 1 grade 3 or higher AE will be compared between the treatment arms using a chi-square test for proportions and confidence intervals for rate difference will be computed using Miettinen-Nurminen (score) methodUp to 6 years
        Post-induction plasma EBV DNA as a prognostic biomarkerWill be defined as a binary biomarker (detectable: \>= 1 copies/mL vs. undetectable: 0 copies/mL). Biomarker effect HRs from multivariable Cox models, including key tumor and patient characteristics will also be reported.Up to 6 years
        Pre-induction plasma EBV DNA vs. progressive disease (PD) during induction treatmentWill include all patients treated with concurrent (induction) treatment and a binary biomarker based on pre-induction plasma EBV DNA (\< 2000 vs. ≥2000 copies/mL). PD rates during induction for each biomarker subgroup will be computed assuming a binomial distribution and compared between biomarker subgroups using a chi-square test. Multivariable Cox models, including key tumor and patient characteristics will also be included.Up to 6 years
        Persistent plasma EBV DNA vs. PFSWill examine the association between persistent EBV DNA after induction treatment and PFS. Only randomized patients with positive pre-induction plasma EBV DNA will be included (\~90-95%). Patients will be classified into "EBV DNA positive to negative" and "EBV DNA consistently positive" based on the pre-induction and post-induction EBV DNA. Multivariable Cox models, including key tumor and patient characteristics will also be included.Up to 6 years
        Are you running this trial?If you're a clinic or sponsor, you can claim this study.
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        References

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

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