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.

The project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 880194.

Eligibility Criteria:
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.
* At least 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
* 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
* 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
* Any history of HIV
* 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)
* 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)
* Any one full cycle of anti-cancer chemotherapy treatment in the 3 preceding weeks of the registration
* 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