Tests engineered T cells for melanoma and head and neck cancer

Trial details

Who runs it

Erasmus Medical Center

Trial code

NCT04729543EU 2024-516922-70-00

Record updated

4 December 2023

Original description

Single-centre, first-in-man phase I/II trial to demonstrate safety and efficacy of MAGE-C2/HLA-A2 TCR T cells (MC2 TCR T cells) in advanced melanoma (MEL) and head-and-neck carcinoma (HNSCC).Read full original descriptionShow less

Adoptive Therapy With TCR Gene-engineered T Cells to Treat Patients With MAGE-C2-positive Melanoma and Head and Neck Cancer

Single-centre, first-in-man phase I/II trial to demonstrate safety and efficacy of MAGE-C2/HLA-A2 TCR T cells (MC2 TCR T cells) in advanced melanoma (MEL) and head-and-neck carcinoma (HNSCC).

Inclusion: 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: 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; 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; 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; 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; Presence of malignant pleural effusion or ascites; 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; Use of any live vaccines against infectious diseases within the last 3 months; Active infection requiring systemic antibiotic therapy at start of study treatment; Women who are pregnant or breastfeeding. A negative pregnancy test before inclusion in the trial is required for all women of child bearing age; Subjects who meet any of the following criteria will be excluded from participation of this study:; 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.

ClinicalTrials.gov NCT04729543 · EU CTIS 2024-516922-70-00