Gene therapy for patients with MAGE-C2-positive melanoma and head and neck cancer.

Phase 1

• Conditions: unresectable stage IIIc and IV melanoma (including unknown primary, mucosal and uveal melanoma), and unresectable recurrent/metastatic(R/M) HNSCC.; MedDRA version: 20.0Level: PTClassification code 10025670Term: Malignant melanoma stage IIISystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: PTClassification code 10071536Term: Head and neck cancer stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: PTClassification code 10071540Term: Head and neck cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0Level: PTClassification code 10025671Term: Malignant melanoma stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2019-000657-31-NL
• Lead Sponsor: Erasmus MC Cancer Institute

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-05-13
• Last Update Posted: 3 November 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

1)patients with inoperable stage IIIc/IV melanoma with progressive disease after standard therapy
2)patients with R/M HNSCC who are ineligible for or unwilling to get platinum-based chemotherapy or for whom no standard treatment is available.
4.2Inclusion criteria
Subjects eligible for inclusion in this study have to meet all of the following criteria:
•Written informed consent must be obtained prior to any screening procedures.
•Male or female must be = 18 years of age at time of providing informed consent.
•One of the following three malignancies:
1.Previously treated for unresectable or metastatic cutaneous or mucosal melanoma for whom no standard treatment is available (anymore):
2.Metastatic uveal melanoma, progressing after standard of care therapy, if available.
3.R/M HNSCC for whom no standard treatment is available anymore.
•Patients must be HLA-A*0201 positive.
•Primary tumor and/or metastasis (archival or fresh biopsy) is positive for MC2 (>1% 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:
oAbsolute neutrophil count greater than 1.5x109/L.
oPlatelet count greater than 75x109/L.
oHemoglobin greater than 5 mmol/L or 8.0 in g/dl.
•Chemistry:
oSerum ALAT/ASAT less than 3 times the upper limit of normal (ULN), unless patients have liver metastases (< 5 times ULN).
oSerum creatinine < 1.5 ULN
oTotal bilirubin less than or equal to 20 micromol/L, except in patients with Gilbert’s Syndrome who must have a total bilirubin less than 50 micromol/L.
•Serology:
oSeronegative for HIV antibody.
oSeronegative for hepatitis B antigen, and hepatitis C antibody.
oSeronegative for lues.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 20
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

•Subjects who meet any of the following criteria will be excluded from participation in this study:
•Presence symptomatic brain metastases. Note: Subjects with symptomatic brain
lesions who have been definitively treated with stereotactic radiation therapy, surgery or gamma knife therapy are eligible.
•Presence of malignant pleural effusion or ascites.
•Systemic chronic steroid therapy (? 10mg/day prednisone or equivalent) or any other immunosuppressive therapy a 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 I 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, cardiac 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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified