Adoptive Therapy With TCR Gene-engineered T Cells to Treat Patients With MAGE-C2-positive Melanoma and Head and Neck Cancer (MC2TCR)

Ziekenhuizen

• Erasmus Medisch Centrum Rotterdam

Doel van het onderzoek

Gecombineerde fase I/II studie.

Fase 1: vaststellen van de maximum tolereerbare dosering van MC2 TCR T cellen.
Fase II: de werkzaamheid (anti-tumor respons) van MC2TCR T cellen

status: open voor inclusie

Behandeling

Toediening van autologe MC2TCR T cellen

Belangrijkste in/exclusiecriteria

Belangrijkste inclusiecriteria:

1. Previously treated for unresectable or metastatic cutaneous, mucosal or uveal melanoma for whom no standard treatment is available (anymore).
   
2. Measurable disease according to RECIST v1.1;
3. At least one lesion, suitable for sequential mandatory tumor biopsies;
4. ECOG performance status of 0 or 1. Life expectancy ≥ 12 weeks;
5. 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;
6. Patients must be HLA-A2*0201 positive*
7. Primary tumor and/or metastasis (archival or fresh biopsy) is positive for MC2 (>5% of tumor cells) according to immunohistochemistry*;

*Deze criteria zullen gedurende de screening in het Erasmus MC onderzocht worden.

Belangrijkste exclusiecriteria:

1. Presence of brain or leptomeningal metastasis. Note: subjects with symptomatic brain lesions who have been definitively treated with stereotactic radiation therapy, surgery, or gamma knife therapy are eligible;
2. Presence of malignant pleural effusion or ascites;
3. 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;
4. 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;
5. 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;
6. 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.

Contactpersoon

Dr. A. van der Veldt, Erasmus MC
Prof. dr. R. Debets, Erasmus MC