Combination treatment of copanlisib and gemcitabine in relapsed/refractory PTCL (COSMOS): An open-label phase 1/2 trial
Mené sur 28 patients atteints d'un lymphome périphérique à cellules T réfractaire ou récidivant, cet essai de phase I/II évalue la dose maximale tolérée du copanlisib (un inhibiteur de PI3K alpha et delta) en combinaison avec la gemcitabine et l'efficacité, du point de vue du taux de réponse, de cette combinaison
Background : Current treatment options for peripheral T-cell lymphomas (PTCLs) in the relapsed/refractory setting are limited and demonstrate modest response rates with rare achievement of complete response (CR). Patients and methods : This phase 1/2 study (NCT03052933) investigated the safety and efficacy of copanlisib, a phosphatidylinositol 3-kinase (PI3K)-
α/-δ inhibitor, in combination with gemcitabine in 28 patients with relapsed/refractory PTCL. Patients received escalating doses of intravenous copanlisib on days 1, 8, and 15, administered concomitantly with fixed-dose gemcitabine (1,000 mg/m2 on days 1 and 8) in a 28-day cycles. Results
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Dose-limiting toxicity was not observed in the dose-escalation phase and 60 mg copanlisib was selected for phase 2 evaluation. Twenty-five patients were enrolled in phase 2 of the study. Frequent grade
≥3 adverse events (AEs) included transient hyperglycemia (57%), neutropenia (45%), thrombocytopenia, (37%), and transient hypertension (19%). However, AEs were manageable, and none were fatal. The overall response rate was 72% with a CR rate of 32%. Median duration of response was 8.2 months, progression-free survival 6.9 months, and median overall survival was not reached. Combination treatment produced a greater CR rate in patients with angioimmunoblastic T-cell lymphoma (AITL) than those with PTCL-not otherwise specified (55.6% vs 15.4%, respectively, P=0.074) and progression-free survival was significantly longer (13.0 vs 5.1 months, respectively, P=0.024). In an exploratory gene mutation analysis of 24 tumor samples, TSC2 mutation was present in 25% of patients and occurred exclusively in responders. Conclusion : Combination copanlisib and gemcitabine is a safe and effective treatment option in relapsed/refractory PTCLs and represents an important new option for therapy in this rare group of patients.
Annals of Oncology 2020