711O - Avelumab + methotrexate to eradicate low-risk gestational trophoblastic tumors in first-line setting: TROPHAMET phase I/II trial

Background

Gestational trophoblastic tumors (GTT) are rare tumors developed in young women during pregnancy. In low-risk GTT characterized by a FIGO score ≤ 6, the standard regimen is the 8-day methotrexate (MTX), known to induce a hCG normalization in ∼70% patients. The immune-checkpoint inhibitor avelumab is active in chemo-resistant disease (You, JCO 2020). The objective was to see if avelumab combined to MTX could increase efficacy, and help eradicate low-risk GTT.

Methods

TROPHAMET was an academic multicenter trial (NCT04396223), led with the French Gestational Trophoblastic Center, meant to assess the safety (run-in phase I) and the efficacy (phase II) of avelumab (800 mg IV, day 1) combined to the 8-day MTX regimen (1 mg/kg/day, days 1; 3; 5; & 7, alternating with folinic acid) on 2 week-cycles. The treatment was administered until hCG-normalization, and then for 3 consolidation cycles. The primary endpoint was the rate of patients with hCG normalization allowing for treatment discontinuation, with a 2-step Simon design (H0, 70%; H1, 90%; α, 5%; power, 80%, 26 required patients).

Results

Between April 2020 and December 2023, 29 patients were enrolled, 27 were treated, and 26 patients were assessable for efficacy (stage I/II/III: 42%/4%/54%; FIGO score 1-2: 31%; 3-4: 31%; 5-6: 38%). They received median 8 treatment cycles (MTX: 3-21; avelumab 2-21). The overall tolerability was favorable. 24 patients (89%) experienced grade 1-3 treatment-related adverse events (TRAEs), including 5 patients (19%) with grade 3. Grade 3 TRAEs comprised stomatitis (n=2), ALT/AST elevation (n=2), and catheter infection (n=1). No grade 4 or 5 TRAEs were reported. A successful hCG normalization was obtained in 96.2% patients (95% CI [85.8-97.3]; n=25/26), after median 3.32 treatment months (IQR 2.51-4.02). With a median 22.0 month follow-up, no subsequent relapse has been observed following treatment discontinuation.

Conclusions

TROPHAMET demonstrates that the combination of avelumab to MTX regimen is feasible, and significantly increases MTX efficacy, as it can cure > 95% of patients with low-risk GTT. This positive trial identifies avelumab + MTX as the new standard regimen. Eradication of this rare pregnancy-related tumor is achievable.

Clinical trial identification

NCT04396223. First posted: May 20, 2020; last update posted: February 29, 2024.

Editorial acknowledgement

Legal entity responsible for the study

Lyon University Hospital.

Funding

Merck.

Disclosure

B. You: Financial Interests, Personal, Advisory Role: Consulting for MSD, AstraZeneca, GSK-Tesaro, Bayer, Roche-Genentech, ECS Progastrine, Novartis, LEK, Amgen, Clovis Oncology, Merck Serono, BMS, Seagen, Myriad, Menarini, Gilead, Eisai, Pharma&. All other authors have declared no conflicts of interest.