Personalized and Cell-based Antitumor Immunization MVX-ONCO-1 in Advanced HNSCC
Personalized and Cell-based Antitumor Immunization MVX-ONCO-1 in Advanced HNSCC
The purpose of this trial is to determine the efficacy of the immunotherapy with MVX-ONCO-1
 in patients with advanced head and neck squamous cell carcinoma. MVX-ONCO-1 consists of dead
 tumor cells from the patient itself and genetically modified cells within a capsule. The
 whole treatment takes 9 weeks. At weeks 1, 2, 3, 4, 6 and 8, the tumor cells are injected
 underneath the skin and two capsules are implanted for a week. At weeks 2, 3, 4, 5, 7 and 9
 the capsules are removed again. The patients are then followed-up for 5 years.
Patients with advanced HNSCC after platinum-based palliative chemotherapy have a poor
 prognosis, with no well-defined standard treatment and a survival between 6 to 9 months.

 MVX-ONCO-1 is a patient specific, cell-based, active immunotherapy, where the patient's
 immune response to tumor cells is stimulated and/or increased by triggering an immune
 response against the patients' cancer cells.

 Rationale for this trial is:

 1. HNSCC: there is a clear medical need in this patient population,

 2. Relapsing HNSCC often have accessible tumor tissue,

 3. HNSCC is considered an immunogenic tumor.

 This phase II study is a first step towards a potentially innovative immunotherapy for HNSCC.

 MVX-ONCO-1 is composed of:

 1. An immune-modulator (GM-CSF: granulocyte-macrophage colony stimulating factor) released
 from an immuno-protected, encapsulated, allogeneic, genetically modified cell line
 (MVX-1), and

 2. Irradiated, autologous tumor cells as source of antigen.

 Each treatment consists of two macrocapsules containing the MVX-1 cell line implanted
 subcutaneously and lethally irradiated autologous tumor cells injected subcutaneously.
 Eligible patients will receive a treatment once weekly starting on week 1 for 4 weeks
 followed by two additional treatments 2 weeks apart (total 6 treatments over 8 weeks). Each
 pair of macrocapsules is removed after 1 week, and the last implanted capsules are removed in
 week 9. The patients are then followed-up for 5 years.
Inclusion Criteria for pre-registration:

 -  Written informed consent according to ICH/GCP regulations before pre-registration

 -  Histologically confirmed diagnosis of head and neck squamous carcinoma (oral cavity,
 pharynx, larynx), Stage III/IV in recurrent or metastatic stage. Patients with local
 relapse for whom a curative treatment is available cannot be enrolled. Furthermore,
 all patients should have no other therapeutic option left.

 -  One line of prior anticancer therapy for recurrent or metastatic disease. Patients
 with locally advanced disease experiencing local relapse within 6 months of last dose
 of curative intended, platinum-based chemo-radiation with or without prior surgery can
 also be included.

 -  Primary tumor and/or metastasis amenable for partial/total surgery or tap

 -  Measurable or evaluable disease according to RECIST 1.1 criteria

 -  Patients age ≥ 18 years

 -  WHO performance status 0-2

 -  Adequate hematological values: neutrophils ≥1x10^9/L, platelets ≥70x10^9/L

 -  Adequate hepatic function: bilirubin ≤2 x ULN; AST and ALT and AP ≤2.5 x ULN (except
 for patients with liver metastasis: ≤5 x ULN)

 -  Adequate renal function (creatinine clearance >40mL/min/1.73m^2, calculated according
 to the corrected formula of Cockcroft-Gault

 -  Foreign protein DTH test positive to at least one antigen

 -  Women with child-bearing potential are using effective contraception, are not pregnant
 and agree not to become pregnant after pre-registration, during trial treatment and
 during the 6 months thereafter. A negative blood pregnancy test before inclusion into
 the trial is required for all women with child-bearing potential

 -  Men agree not to father a child during trial treatment and during 6 months thereafter

 Exclusion Criteria for pre-registration:

 -  Known or suspected CNS metastases or active leptomeningeal disease

 -  History of hematologic or primary solid tumor malignancy, unless in remission for at
 least 3 years from registration with the exception of T1-2 prostate cancer Gleason
 score <6 (PSA<10 ng/mL), adequately treated cervical carcinoma in situ or localized
 non-melanoma skin cancer

 -  Participated in any other investigational study or received an experimental
 therapeutic procedure considered to interfere with the study in the 4 preceding weeks
 of the pre-registration

 -  Any chemotherapy treatment in the 4 preceding weeks of the pre-registration

 -  Concomitant use of other anti-cancer drugs

 -  Planned radiotherapy (other than symptom control)

 -  Severe or uncontrolled cardiovascular disease uncontrolled hypertension (sustained
 systolic blood pressure > 150 mm Hg and/or diastolic > 100 mm Hg despite
 antihypertensive therapy)

 -  History of cerebrovascular accident or intracranial hemorrhage within 6 months prior
 to pre-registration

 -  Positive HIV test

 -  Known history of HTLV-1, HTLV-2, or active chronic Hepatitis C or Hepatitis B Virus
 infection or any uncontrolled active systemic infection requiring intravenous (iv)
 antimicrobial treatment

 -  Known severe allergy to reagents in the study product (MVX-ONCO-1) such as penicillin,
 streptomycin

 -  Systemic disease other than cancer that is not controlled by approved medication

 -  Patient with active autoimmune disease

 -  Chronic immunosuppressive treatment exceeding 20 mg/day of prednisone or an equivalent
 corticosteroid. Note: In acute situations prednison exceeding 20mg/day or
 equivalent(day is allowed during 7 days)

 -  Women who are pregnant or breast feeding

 -  Any other serious underlying medical, psychiatric, psychological, familial or
 geographical condition, which in the judgment of the investigator may interfere with
 the planned staging, treatment and follow-up, affect patient compliance or place the
 patient at high risk from treatment-related complications

 Inclusion criteria for registration:

 -  Primary tumor and/or metastasis amenable for partial/total surgery or tap and
 subsequent cell harvest > 26x10^6 cells

 -  Measurable or evaluable disease according to RECIST 1.1 criteria

 -  WHO performance status 0-2

 -  Baseline QoL forms have been completed

 -  Adequate hematological values: neutrophils ≥1x10^9/L, platelets ≥70x10^9/L

 -  Adequate hepatic function: bilirubin ≤2 x ULN; AST and ALT and AP ≤ 2.5 x ULN (except
 for patients with liver metastasis: ≤5 x ULN)

 -  Adequate renal function (creatinine clearance >40 mL/min/1.73m^2, calculated according
 to the corrected formula of Cockcroft-Gault

 -  Women with child-bearing potential are using effective contraception, are not pregnant
 or lactating and agree not to become pregnant after registration, during trial
 treatment, and during the 6 months thereafter. A negative blood pregnancy

 Exclusion criteria for registration:

 -  Known or suspected CNS metastases or active leptomeningeal disease

 -  Concomitant use of other anti-cancer drugs

 -  Planned radiotherapy (other than symptom control)

 -  Systemic disease other than cancer, that is not controlled by approved medication

 -  Chronic immunosuppressive treatment exceeding 20 mg/day of prednisone or an equivalent
 corticosteroid. Note: In acute situations prednisone exceeding 20 mg/day or equivalent
 is allowed during 7 days

 -  Any other serious underlying medical, psychiatric, psychological, familial or
 geographical condition, which in the judgment of the investigator may interfere with
 the planned staging, treatment and follow-up, affect patient compliance or place the
 patient at high risk from treatment-related complications

 -  Women who are pregnant or breastfeeding