Phase II clinical trial of amatuximab, a chimeric anti-mesothelin antibody with pemetrexed and cisplatin in advanced unresectable pleural mesothelioma
Mené sur 89 patients atteints d'un mésothéliome pleural malin non résécable, cet essai de phase II évalue l'efficacité, du point de vue de la survie sans progression à 6 mois, et la toxicité de l'amatuximab en combinaison avec du pemetrexed et du cisplatine
Purpose:Amatuximab is a chimeric monoclonal antibody to mesothelin, a cell surface glycoprotein highly expressed in malignant pleural mesothelioma (MPM). Based on its synergy with chemotherapy in pre-clinical studies, we evaluated the antitumor activity of amatuximab plus pemetrexed and cisplatin in patients with unresectable MPM. Experimental Design:In a single-arm phase II study, amatuximab 5 mg/kg was administered on days 1 and 8 with pemetrexed, 500 mg/m2 and cisplatin, 75 mg/m2 on day 1 of 21-day cycles for up to 6 cycles. Patients with response or stable disease received amatuximab maintenance until disease progression. Primary endpoint was 6 months progression-free survival (PFS). Secondary endpoints were overall survival (OS), response rate and safety. Results:Eighty nine patients were enrolled at 26 centers. Median of five cycles (range 1-6) of combination treatment was administered and 56 (63%) patients received amatuximab maintenance. Combination therapy resulted in no overlapping toxicities. Eleven patients (12.4%) had amatuximab-related hypersensitivity reactions. Responses included partial responses in 33 (40%) and stable disease in 42 (51%). Six month-PFS rate was 51% (95% CI: 39.1, 62.3), median PFS 6.1 months (95% CI: 5.8, 6.4) and median OS 14.8 months (95% CI: 12.4, 18.5) with 29 patients alive at data cut-off. Conclusions:Amatuximab with pemetrexed and cisplatin was well-tolerated with objective tumor response or stable disease rate of 90% by independent radiological review. Although PFS was not significantly different from historical controls, the median OS was 14.8 months with a third of patients alive and 5 continuing to receive amatuximab at the time of analysis. -