Patient case: 60-year-old female with gastric cancer; genetic feature: EGFR

Clinical trial: Reactivating NK Cells in Treating Refractory Head and Neck Cancer

Summary: This study aims to determine the safety and efficacy of expanded activated autologous NK cells administered after cetuximab in patients with EGFR-positive nasopharyngeal carcinoma or head and neck squamous cell carcinoma.

Detailed description: Natural killer (NK) cells are cytotoxic lymphocytes of the innate immune system that are responsible for direct and indirect cytolytic killing of virally-transformed and/or cancer cells. Harnessing NK cells in cancer immunotherapy therefore, provides a direct cytotoxic effect on cancer cells which further stimulates further downstream adaptive anti-tumor immune responses against the cancer. In order to effect a more targeted killing of these tumor cells, using a monoclonal antibody (mAb) to direct these NK cells to the target site is feasible, provided a specific tumor antigen can be identified. In nasopharyngeal Carcinoma (NPC) and head and neck squamous cell carcinoma (HNSCC) where epidermal growth factor receptor (EGFR) is ubiquitously expressed, combining NK cell therapy with cetuximab (a chimeric mouse/human anti-EGFR monoclonal antibody) to direct these NK cells against these EGFR tumor targets is possible. In this study, we seek to enhance the antitumor activity of cetuximab to treat EGFR-positive head and neck cancers by combing infusion of activated expanded autologous NK cells with cetuximab. Patients selected for this trial are those with refractory NPC and HNSCC where no feasible therapeutic options are available. This is a lead-in phase I followed by a phase II study. The phase I study will enroll 9 patients and will test the feasibility and safety of this combination strategy and determine the tolerated dose of NK cell infusion (1x1^06/kg or 1x10^7/kg NK cells) in adult EGFR positive NPC and HNSCC patients. For the first 3 patients, each new patient will only be enrolled at least 3 weeks after treatment of the preceding patient to allow sufficient time to monitor toxicities. Initial phase of treatment consists of 7 weeks of cetuximab monotherapy. At week 8, clinical evaluation will be done to determine patients who are suitable to continue this study with NK cell therapy, based on the severity of toxicities encountered. Eligible patients will undergo apheresis (Day -10) to harvest NK cells. The collected NK cells will be expanded and activated in the laboratory. During cycle 1, cetuximab will be given on day 1 with subcutaneous IL-2 (three times per week for 2 weeks); followed by expanded NK cells on day 2. The purpose of IL-2 is to sustain activity of these NK cells in-vivo. Cetuximab will be administered weekly for additional 2 weeks following the NK cell infusion during cycle 1. For cycle 2 and 3, cetuximab monotherapy will be administered every 21 days. Clinical evaluation will be performed upon completion of cycle 3. Patients with stable disease or with partial response will be allowed to continue with a second NK infusion dose as per cycle 1, followed by additional 2 more cycles of cetuximab monotherapy (every 21 days).

Eligibility: Inclusion Criteria:
  1. Age >21
  2. Histologically confirmed diagnosis of WHO type III (undifferentiated) EGFR-positive nasopharyngeal carcinoma or EGFR-positive head and neck squamous cell carcinoma (based on >80% immunohistochemistry stain on tissue biopsy)
  3. Recurrent cancer that is not surgically salvageable
  4. Metastatic disease (after one course of palliative chemotherapy has been completed)
  5. Presence of measurable tumor by RECIST 1.1 criteria
  6. At least two weeks since receipt of any biological therapy, chemotherapy, and/or radiation
  7. Adequate organ function:
  -  ANC ≥ 1500/µL
  -  Platelet count ≥ 100,000/µL
  -  Creatinine clearance ≥60ml/minute
  -  Total bilirubin ≤ 1.5 x upper limit normal
  -  AST ≤ 5 x upper limit normal
  -  ALT ≤ 5 x upper limit normal
  8. ECOG performance status of 0-1
  9. Life expectancy of at least 60 days
  Exclusion Criteria:
  1. Treatment within the last 30 days with any investigational drug
  2. Concurrent administration of any other tumor therapy, including cytotoxic chemotherapy, hormonal therapy, and immunotherapy
  3. Major surgery within 28 days of study drug administration
  4. Active infection that in the opinion of the investigator would compromise the patient's ability to tolerate therapy
  5. Lactating or pregnant
  6. Second primary malignancy that is clinically detectable at the time of consideration for study enrolment
  7. Receipt of steroids during time period of 3 days prior to expanded NK cell infusion to 30 days after infusion (i.e. day -3 to day +30).
  8. Symptomatic brain metastases
  9. Serious concomitant disorders that would compromise the safety of the patient or compromise the patient's ability to complete the study, at the discretion of the investigator; serious cardiac illness or medical conditions including but not limited to:
  -  Patients with dyspnea at rest.
  -  History of documented congestive heart failure
  -  High risk uncontrolled arrhythmias
  -  Angina pectoris requiring a medicinal product
  -  Clinically significant valvular disease
  -  Poorly controlled hypertension

Relevance to patient case: not relevant