Phase II study of ceralasertib (AZD6738) in combination with durvalumab in patients with advanced/metastatic melanoma who have failed prior anti-PD1 therapy
Mené sur 30 patients atteints d'un mélanome de stade avancé ou métastatique, cet essai de phase II évalue l'efficacité, du point de vue du taux de réponse globale et du taux de contrôle de la maladie, et la toxicité du céralasertib (un inhibiteur d'ATR dispensé par voie orale) en combinaison avec le durvalumab, après l'échec d'une thérapie à base d'anti-PD1
Résumé en anglais
Background : Modulating the DNA damage response and repair (DDR) pathways is a promising strategy for boosting cancer immunotherapy. Ceralasertib (AZD6738) is an oral inhibitor of the serine/threonine protein kinase ataxia telangiectasia and Rad3 related protein, which is crucial for DDR.
Patients and methods : This phase II trial evaluated ceralasertib plus durvalumab for the treatment of patients with metastatic melanoma (MM) who had failed anti-PD1 therapy.
Results : Among the 30 patients, we observed an overall response rate of 31.0% and a disease control rate of 63.3%. Responses were evident across patients with acral, mucosal, and cutaneous melanoma. The median duration of response was 8.8 months (range, 3.8–11.7). The median progression-free survival was 7.1 months (95% confidence interval, 3.6–10.6) and the median overall survival was 14.2 months (95% confidence interval, 9.3–19.1). Common adverse events were largely hematologic and manageable with dose interruptions and reductions. Exploratory biomarker analysis suggested that tumors with an immune-enriched microenvironment or alterations in the DDR pathway were more likely to respond to the study treatment.
Conclusion : We conclude that ceralasertib in combination with durvalumab has promising anti-tumor activity among patients with MM who have failed anti-PD1 therapy, and constitute a population with unmet needs.
