In GTN patients resistant to chemotherapy, standard treatments include historic single agent or polychemotherapy regimens, known to be effective (65%-95% successful hCG normalization) and toxic. PD-L1 is constitutively expressed in all GTN subtypes (Bolze et al. Int J Gynecol Cancer 2017). The objective of TROPHIMMUN trial is to assess the efficacy of the anti-PD-L1 monoclonal antibody avelumab (Pfizer & Merck Serono) in patients with chemoresistant GTN.
In this multicenter trial (NCT03135769) activated in February 2017, avelumab is given at 10 mg/kg every 2 weeks in patients with GTN resistant to monochemotherapy (cohort A) or to polychemotherapy (cohort B). Avelumab is prescribed until hCG normalization, and for 3 additional cycles thereafter. The primary endpoint is the rate of patients with hCG normalization, following a 2 step Simon design. The outcomes of the intermediate efficacy analysis planned after enrollment of 6 cohort A patients are presented.
As of September 2018, 13 patients have been enrolled (27-47 years old, median: 33): 9 patients in cohort A; 4 patients in cohort B. Cohort A patients had: invasive moles (100%), stage I (78%) or stage III (22%); FIGO score 1-4 (56%) or 5-6 (44%) diseases; prior resistances to methotrexate (100%) & to actinomycine-D (11%). Among them, 7 patients (78%) experienced 62 adverse events: grade 1 (83.9%); grade 2 (14.5%, including 1 hypothyroidism); grade 3 (1 metrorragia disease-related). Among the first 6 patients assessed for planned intermediate analysis, 3 patients normalized hCG, and stopped treatment without any further sign of relapse (10.7 month follow-up). The other hCG declines observed in subsequently recruited patients are to be confirmed.
There is a strong rational for investigating immunotherapies in GTN patients. TROPHIMMUN trial preliminary outcomes suggest that avelumab might be effective, and better tolerated than standard chemotherapy in patients with resistance to single chemotherapy. This is the first clinical trial reporting potential cures with a non-chemotherapy agent in patients with this rare cancer.
Clinical trial identification
EudraCT Number: 2016-002322-37