Avelumab and Methotrexate in in Low-risk Gestational Trophoblastic Neoplasias as First Line Treatment
Status:
Recruiting
Trial end date:
2026-07-12
Target enrollment:
Participant gender:
Summary
Gestational trophoblastic neoplasias (GTN) are characterized by the persistence of elevated
hCG titers after complete uterine evacuation of a partial hydatidiform mole (PHM) or a
complete hydatidiform mole.
Low-risk GTN patients (FIGO score ≤ 6) are commonly treated with single agent treatment
(methotrexate or actinomycin-D) The cure rate, assessed by hCG normalization, is obtained in
65 to 75% of patients with these agents GTN patients with resistance to these treatments are
treated with another single agent drug or polychemotherapy regimens, such as EMA-CO or BEP
regimen.
Chemotherapy standard regimens are old and toxic for these young lady patients, with
potential long term effects detrimental for further maternity and quality of life
There is a strong rational for investigating the anti-PDL1 monoclonal antibody avelumab in
chemoresistant GTN patients. Several elements suggest that the normal pregnancy immune
tolerance is "hijacked" by GTN cell for proliferating :
- Spontaneous regressions of metastastic GTN are regularly observed, thereby the role of
immune system for rejecting GTN cells.
- Strong and constant overexpression of PDL1 and NK cells has been found in all subtypes
and settings of GTN tumors from French reference gestational trophoblastic center.
- Complete and durable responses to pembrolizumab were reported in 3 patients with
multi-chemoresistant GTN in United Kingdom.
- Three cases of hCG normalization with avelumab in 6 patients with chemo-resistant GTN
enrolled in TROPHIMMUN cohort A (resistant to a mono-chemotherapy).
- Cytotoxicity of avelumab is mediated through antibody dependent cell cytotoxicity (ADCC)
by NK cells.
Phase:
Phase 1/Phase 2
Details
Lead Sponsor:
Hospices Civils de Lyon
Collaborator:
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany