Combined Therapy of Nivolumab and Adoptive T Cell Therapy in Metastatic Melanoma Patients (Nivo-TIL)

  • End date
    Jan 11, 2024
  • participants needed
  • sponsor
    Nantes University Hospital
Updated on 11 May 2022
metastatic melanoma
gilbert's syndrome
neutrophil count
tumor cells
brain metastases
braf inhibitor
braf v600 mutation
immunologic adjuvant
ocular melanoma


To improve the efficacy of immunotherapy for cancer, recent studies focused on specific targets to redirect the immune network toward eradicating a variety of tumors and ameliorating the self-destructive process.

A clinically relevant immune escape mechanism in melanoma is the activation of the Programmed cell Death-1 (PD-1) receptor on infiltrating T cells. By blocking PD-1 receptors with anti-PD-1 monoclonal antibodies (mAbs), T-cells are unaffected by the PD-L1 expressed on tumor cells and the patients T cells are free to respond to melanoma antigens and attack tumor cells. So the objective of this trial is to evaluate the safety and the efficacy of a combined therapy Nivolumab and adoptive T cell therapy in metastatic melanoma patients.

Condition Melanoma
Treatment TIL + IL-2 + Nivolumab
Clinical Study IdentifierNCT03374839
SponsorNantes University Hospital
Last Modified on11 May 2022


Yes No Not Sure

Inclusion Criteria

over 18 years old with a weight ≥ 40 kg
Patients must have signed informed consent
Patients with stage IIIb, IIIc or IV metastatic melanoma (AJCC 6th edition) with at least two lesions (lymph nodes relapse, or in transit metastasis, or unresectable cutaneous metastases, or visceral metastases except bone and brain metastases) including one easily accessible and no more than 2 lines of treatment of melanoma at the metastatic stage
Patients with a melanoma expressing a Braf V600 mutation can be included
Measurable/assessable disease in 28 days which precede the first administration of the treatment
A negative pregnancy test for women with childbearing potential
Eastern Cooperative Oncology Group (ECOG) of 0-1, Karnofsky > 80%
Laboratory results
Haemoglobin ≥ 10 g/dl or ≥ 6,25 mmol/l; Neutrophils ≥ 1500/μl; Leukocytes ≥ 4000/μl
Lymphocytes ≥ 700/μl; Blood platelet ≥ 100.000/μl; Serum creatinine ≤ 1.5 x superior normal
value or creatinine clearance (CrCl) ≥ 40 mL/min (if using the Cockcroft-Gault formula)
Serum bilirubin ≤ 2.0 mg/dl or ≤ 34.2 mol/l; Total bilirubin ≤ 1.5 x superior normal value
(except subjects with Gilbert Syndrome, who can have total bilirubin < 3mg/dL); Aspartate
aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 2 x superior normal value
Lactate dehydrogenase (LDH) ≤ 1.5 x superior normal value
Subjects affiliated to an appropriate health insurance
Women of childbearing potential (WOCBP) must use appropriate method(s) of
contraception during the clinical trial. Furthermore WOCBP will be instructed to
adhere to contraception for a period of 5 months after the last dose of Nivolumab
Men who are sexually active with WOCBP will be instructed to adhere to contraception
Non inclusion Criteria
during the clinical trial and for a period of 7 months after the last dose of
Brain or bone metastases
Ocular melanoma
Women who are not of childbearing potential (ie, who are postmenopausal or surgically
sterile) as well as azoospermic men do not require contraception
Contraindication for the use of vasopressor agents
For female: the patient is pregnant or breastfeeding or not using contraception
For men: the patient is sexually active with WOCBP and not using contraception
Chemotherapy or radiotherapy within 4 weeks before baseline (6 weeks for nitroso-ureas
and mitomycin C)
History of allergies and Adverse Drug Reaction
Hypersensitivity to human albumin, TIL excipient
Hypersensitivity to Nivolumab or related excipients
History or current manifestations of severe progressive heart disease (congestive
History of severe hypersensitivity reaction to any monoclonal antibody
heart failure, coronary artery disease, uncontrolled arterial hypertension, serious
Hypersensitivity to aldesleukin or to one of Proleukin excipients
rhythm disorders or ECG signs of previous myocardial infarction)
Patients should be excluded if they have had prior treatment with an anti-PD-1
History of uveitis or melanoma-associated retinopathy
anti-PD-L1, anti-PD-L2, anti-CTLA4 antibody, or any other antibody or drug
specifically targeting T-cell costimulation or immune checkpoint pathways except in
Unchecked thyroid dysfunction
the context of adjuvant or neoadjuvant
History of chronic autoimmune disease (Addison's disease, multiple sclerosis, Graves'
disease, rheumatoid arthritis, systemic lupus erythematosus, etc…) except patient with
active vitiligo or a history of vitiligo
History of inflammatory bowel disease, celiac disease, or other chronic
gastrointestinal conditions associated with diarrhea
Presence of a second active cancer, with the exception of an in situ cervical cancer
or a skin cancer different from the treated melanoma
Any serious, acute or chronic illness id est active infection asking for antibiotics
administration, coagulation's disorders, or any state asking for an unauthorized
concomitant treatment described in this study
Patients should be excluded if they have a condition requiring systemic treatment with
either corticosteroids (> 10 mg daily prednisone equivalents) or other
immunosuppressive medications within 14 days before study drug administration. Inhaled
or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents
are permitted in the absence of active autoimmune disease. Subjects are permitted to
use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids
(with minimal systemic absorption). Physiologic replacement doses of systemic
corticosteroids are permitted, even if > 10 mg/day prednisone equivalents. A brief
course of corticosteroids for prophylaxis (eg, contrast dye allergy) or for treatment
of nonautoimmune conditions (eg, delayed-type hypersensitivity reaction caused by
contact allergen) is permitted
Adults under a legal protection regime (guardianship, trusteeship, "sauvegarde de

Exclusion Criteria

Positive viral serology for HIV (human immunodeficiency virus) 1/2, p24 Ag, HTLV1, HTLV2
B and C hepatitis or syphilis
Clear my responses

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