personalized and cell-based antitumor immunization mvx-onco-1 in advanced hnscc

Conditions: Head and Neck Squamous Cell Carcinoma

Summary: 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

Keywords: head and neck squamous cell carcinoma cancer hnscc immunotherapy mvx-onco-1