Inclusion Criteria:
* \- Woman older than 18 years
* Low-risk gestational trophoblastic neoplasia according to FIGO score (FIGO score ≤ 6) with indication of methotrexate as first line treatment
* Patients with Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
* Patients with adequate bone marrow function measured within 28 days prior to administration of study treatment as defined below
* Absolute granulocyte count ≥ 1.5 x 10 9 /L
* Platelet count ≥ 100 x 10 9 /L
* Haemoglobin ≥ 9.0 g/dL (may have been blood transfused)
* Patients with adequate renal function:
\* Calculated creatinine clearance ≥ 30 ml/min according to the Cockcroft-Gault formula (or local institutional standard method)
* Patients with adequate hepatic function
\*Serum bilirubin ≤ 1.5 x UNL and AST/ALT ≤ 2.5 X UNL (≤ 5 X UNL for patients with liver metastases)
* Patients must have a life expectancy ≥ 16 weeks
* Confirmation of non-childbearing status for women of childbearing potential.
An evolutive pregnancy can be ruled out in the following cases:
* in case of a previous hysterectomy
* if serum hCG level ≥ 2 000 IU/L and no intra or extra-uterine gestational sac is detected on pelvic ultrasound
* if serum hCG level \< 2 000 IU/L on a first measurement and serum hCG increases \<100% on a second measurement performed 3 days later.
* Highly effective contraception if the risk of conception exists. (Note: The effects of the trial drug on the developing human fetus are unknown; thus, women of childbearing potential must agree to use 2 highly effective contraceptions, defined as methods with a failure rate of less than 1 % per year. Highly effective contraception is required at least 28 days prior, throughout and for at least 12 months after avelumab treatment.
* Patients who gave its written informed consent to participate to the study
* Patients affiliated to a social insurance regime
* Patient is willing and able to comply with the protocol for the duration of the treatment
Exclusion Criteria:
* Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti- CTLA 4 antibody (including ipilimumab, tremelimumab or any other antibody or drug specifically targeting T-cell costimulation or immune checkpoint pathways).
* Illness, incompatible with avelumab, such as congestive heart failure; respiratory distress; liver failure; uncontrolled epilepsy; allergy.
* Patients with a known allergic hypersensitivity to methotrexate or any of the other ingredients (sodium chloride, sodium hydroxide, and hydrochloric acid if excipient)
* Patients with second primary cancer, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for ≥ 5 years.
* All subjects with brain metastases, except those meeting the following criteria:
* Brain metastases that have been treated locally and are clinically stable for at least 2 weeks prior to enrolment, No ongoing neurological symptoms that are related to the brain localization of the disease (sequelae that are a consequence of the treatment of the brain metastases are acceptable).
* Subjects with brain metastases must be either off steroids except a stable or decreasing dose of \<10mg daily prednisone (or equivalent).
* Patients receiving any systemic chemotherapy, radiotherapy (except for palliative reasons), within 2 weeks from the last dose prior to study treatment (or a longer period depending on the defined characteristics of the agents used). The patient can receive a stable dose of bisphosphonates for bone metastases, before and during the study as long as these were started at least 4 weeks prior to treatment with study drug.
* Persistent toxicities (\>=CTCAE grade 2) with the exception of alopecia and sensory neuropathy, caused by previous cancer therapy.
* Treatment with other investigational agents.
* Bowel occlusive syndrome, inflammatory bowel disease, immune colitis, or other gastro-intestinal disorder that does not allow oral medication such as malabsorption.
* Stomatitis, ulcers of the oral cavity and known active gastrointestinal ulcer disease
* Clinically significant (i.e., active) and severe cardiovascular disease according to investigator opinion such as myocardial infarction (\< 6 months prior to enrollment)
* Patients with immune pneumonitis, pulmonary fibrosis
* Known severe hypersensitivity reactions to monoclonal antibodies, any history of anaphylaxis, or uncontrolled asthma (ie, 3 or more features of partially controlled asthma Global Initiative for Asthma 2011).
* Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness.
* Active infection requiring systemic therapy.
* Positive test for HBV surface antigen and / or confirmatory HCV RNA (if anti-HCV antibody tested positive)
* Administration of a live vaccine within 30 days prior to study entry.
* Current or prior use of immunosuppressive medication within 7 days prior to start of study treatment.
The following are exceptions to this exclusion criterion:
* Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra-articular injection);
* Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or equivalent;
* Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication).
* Active autoimmune disease that might deteriorate when receiving an immunostimulatory agents.
Patients with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible.
* Female patients who are pregnant or lactating, or are of childbearing potential and not practicing a medically acceptable method of birth control.
* Treatment with oral anticoagulant such Coumadin.
* Alcoholism (patient interview, investigator judgment)
* Resting ECG with QTc \> 470msec on 2 or more time points within a 24 hour period or family history of long QT syndrome. Torsades de Pointes, arrhythmias (including sustained ventricular tachyarrhythmia and ventricular fibrillation, bradycardia defined as \<50 bpm), right bundle branch block and left anterior hemiblock (bifascicular block), unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure (CHF New York Heart Association Class III or IV), cerebrovascular accident, transient ischemic attack or symptomatic pulmonary embolism.
* Prior organ transplantation, including allogeneic stem cell transplantation (excluding autologous bone marrow transplant)
* Patients under guardianship.
