Education and Training

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

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 grow or spread longer than the usual approach in patients with recurrent or metastatic nasopharyngeal cancer.

Stanford is currently accepting patients for this trial.

Intervention(s):

  • 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

Eligibility


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 for recurrent/metastatic (R/M) NPC including cytotoxic
   chemotherapy. Prior treatment for non-recurrent and non-metastatic NPC is allowed.

   - 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. This includes RT given
   with palliative intent to recurrent/metastatic sites. The irradiated sites 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.

Ages Eligible for Study

18 Years - N/A

Genders Eligible for Study

All

Now accepting new patients

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Elizabeth Winters
650-721-6509
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