Testing the Addition of BMS-986016 (Relatlimab) to the Usual Immunotherapy After Initial Treatment for Recurrent or Metastatic Nasopharyngeal Cancer
NCT06029270 · Phase 2 · Dublin, California, United States
- Condition
- Head and Neck Cancer
- Disease stage
- Stage I-IV
- Phase
- Phase 2
- Study type
- PROCEDURE, DRUG, BIOLOGICAL
- Intervention
- Carboplatin, Cisplatin, Gemcitabine
- Age
- 18 Years to
- Gender
- All
- Sponsor
- National Cancer Institute (NCI)
- Research institution
- National Cancer Institute (NCI)
- Facility
- Kaiser Permanente Dublin
- Research center
- Kaiser Permanente Dublin
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.
Inclusion criteria
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. Syste
Primary outcomes
Progression-free survival (PFS)
Secondary outcomes
Overall survival (OS); Tumor response; Locoregional failure