MAGE-C2 TCR T Cell Trial to Treat Melanoma and Head and Neck Cancer

Inclusion criteria

• Written informed consent;
• Age ≥ 18 years;
• One of the following three malignancies:
• Previously treated for unresectable or metastatic cutaneous or mucosal melanoma for whom no standard treatment is available (anymore);
• Metastatic uveal melanoma, progressing after standard of care therapy, if available;
• R/M HSNCC for whom no standard treatment is available anymore;
• Patients must be HLA-A2\*0201 positive;
• Primary tumor and/or metastasis (archival or fresh biopsy) is positive for MC2 (\>5% of tumor cells) according to immunohistochemistry;
• Measurable disease according to RECIST v1.1;
• At least one lesion, suitable for sequential mandatory tumor biopsies;
• ECOG performance status of 0 or 1. Life expectancy ≥ 12 weeks;
• Patients with melanoma must have had objective evidence of disease progression while on or after standard systemic therapy. The last dose of prior therapy (e.g. anti- PD-1, chemotherapy) must have been received more than 4 weeks prior to the start of study treatment. For melanoma patients who are treated with BRAF- and MEK inhibitors, an interval of 2 weeks between discontinuation of BRAF- and MEK inhibition and start of study treatment is sufficient;
• Patients with R/M HNSCC must have had objective evidence of disease progression and are ineligible for or unwilling to get platinum-based chemotherapy or for whom no standard treatment is available;
• Patients of both genders must be willing to practice a highly effective method of birth control during treatment and for four months after receiving the preparative regimen;
• Patients must meet the following laboratory values at the screening visit in the absence of growth factors and/or transfusion support:
• Hematology:
• absolute neutrophil count greater than 1.5x10\^9/L;
• platelet count greater than 75x10\^9/L;
• hemoglobin greater than 5 mmol/L or 8.0 in g/dl;
• Chemistry:
• serum ALAT/ASAT less than 3 times the upper limit of normal (ULN), unless patients have liver metastasis (\<5 times ULN);
• serum creatinine \< 1.5 ULN;
• total bilirubin ≤ 20 micromol/L, except in patients with Gilbert's Syndrome who must have a total bilirubin ≤ 50 micromol/L;
• Serology:
• seronegative for HIV antibody;
• seronegative for hepatitis B antigen, and hepatitis C antibody;
• seronegative for lues.

Exclusion criteria

• Subjects who meet any of the following criteria will be excluded from participation of this study:
• presence of symptomatic brain metastasis. Note: subjects with symptomatic brain lesions who have been definitively treated with stereotactic radiation therapy, surgery, or gamma knife therapy are eligible;
• Presence of active brain metastasis defined as new or progressive brain metastasis at the time of study entry. Note: subjects with treated or stable brain metastasis are eligible;
• Presence of leptomeningeal metastasis;
• Presence of malignant pleural effusion or ascites;
• Systemic chronic steroid therapy (\>10 mg/day prednisone or equivalent) or any other immunosuppressive therapy within 7 days prior to leukapheresis or 72 hours prior to infusion of the MC2 TCR T cells. Note: local steroids such as topical, inhaled, nasal and ophthalmic steroids are allowed;
• Active, known or suspected autoimmune disease or a documented history of autoimmune disease. Note: subjects with vitiligo, controlled type 1 diabetes mellitus on stable insulin dose, residual autoimmune-related hypothyroidism only requiring hormone replacement or psoriasis not requiring systemic treatment are permitted;
• Any active systemic infections, coagulation disorders or other active major medical illnesses, such as active autoimmune diseases requiring anti-TNF treatment;
• History of myocardial infarction, cardial angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 6 months of enrollment;
• AEs of previous treatment. Toxicities associated with prior systemic and non- systemic treatment must have recovered to a grade 1 or less. Patients may have undergone minor surgical procedures or palliative radiotherapy (for non-target lesions) within the past 4 weeks, as long as all toxicities have recovered to grade 1 or less;
• Women who are pregnant or breastfeeding. A negative pregnancy test before inclusion in the trial is required for all women of child bearing age;
• Use of any live vaccines against infectious diseases within the last 3 months;
• Active infection requiring systemic antibiotic therapy at start of study treatment;
• Prior allogenic bone marrow or solid organ transplant;
• History of known hypersensitivity to any of the investigational drugs used in this study;
• Malignant disease, other than being treated in this study. Exceptions to this exclusion include the following: malignancies that were treated curatively and have not recurred within 2 years prior to start of study treatment, completely resected basal cell and squamous cell skin cancers and any completely resected carcinoma in situ.