Avelumab and Methotrexate in in Low-risk Gestational Trophoblastic Neoplasias as First Line Treatment

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.

Timeline

Start

2020-02-12

Primary completion

2025-04-12

Completion

2028-10-12

Publications

• You B, Lotz JP, Descargues P, Joly F, De La Motte Rouge T, Lebreton C, Gladieff L, Follana P, Jamelot M, Massardier J, Hajri T, Msika A, Alves-Ferreira M, Bin S, Langlois-Jacques C, Subtil F, Roux A, Desauw C, Provansal M, Schwiertz V, Golfier F, Bolze PA. Avelumab Plus Methotrexate for Gestational Trophoblastic Tumors: The TROPHAMET Phase 1/2 Nonrandomized Clinical Trial. JAMA Oncol. 2026 Jun 11:e261697. doi: 10.1001/jamaoncol.2026.1697. Online ahead of print.

Drugs

Indications