Abstract CT402: A phase I study of inotuzumab ozogamicin (IO) in combination with temsirolimus (T) in patients (pts) with relapsed or refractory (R/R) CD22-positive (pos) B-cell non-Hodgkin lymphomas (NHL)
Authors: Stathis Anastasios , Hitz Felicitas , Novak Urban , Bertoni Francesco , Terrot Tatiana , Moser Laura , Xenidou Ioanna , Mazzucchelli Luca , Ghielmini Michele , Sessa Cristiana , Zucca Emanuele , Cavalli Franco 
Published: May 2015

Abstract
Background: IO, an anti-CD22 monoclonal antibody conjugated to the chemotherapy agent calicheamicin and T, an mTOR inhibitor, have single agent activity in B-cell NHL. The purpose of the study is to assess the safety, tolerability, recommended phase II dose and preliminar antitumor activity of their combination.
Materials and methods: Patients with CD22pos, R/R B-cell NHL, with no limits on previous treatments are eligible. Initial study design consisted of treatment with IO on day(d) 1 in combination with weekly T, in cycles q28d.
Results: To date, 10 pts have been screened and 5 CD22pos pts have been entered in dose levels 1 and -1. Demographics: median age 60 (range 40-75), F:M= 1:4, ECOG 0:1= 1:4, lymphoma subtype: diffuse large B-cell=2, follicular=2, mantle cell=1, median number of previous systemic treatments 4.6 (range 2-9). Patients received a total of 10 cycles of the combination with a median of 2 cycles (range 1-3). Adverse events (AE) of grade 3 or higher of at least possible attribution to the study treatment were neutropenia (3pts), thrombocytopenia (4pts), epistaxis (1pt), AST/ALT increase (1pt), macular rash (1pt), suspected capillary leak syndrome (1pt), abdominal pain (1pt), hypophosphatemia (2pts), hypertriglyceridemia (1pt), hypokalemia (1pt). Dosing limited toxicities (DLT) consisted in thrombocytopenia, hypertriclyceridemia and inability to receive at least 3 doses of T during cycle 1. Four patients were evaluable for response: 1 partial remission (PR) and 3 stable disease (SD) were observed after 2 cycles of treatment.
Conclusion: A weekly administration of T in combination with IO on d1 is not feasible due to toxicities. Clinical activity has been observed in heavily pretreated patients not responding to standard treatments. An alternative treatment schedule without dose escalation of IO given on d1 and escalating T doses given 3/4 weeks will be evaluated.
Dose limiting toxicities
Dose levelInotuzumab Ozogamicinmg/m2 d1Temsirolimusmgd1,8,15,22Total no. of cyclesNo of pts with DLT/Total no. of ptsNature of DLT10.81592/4• Gr 4 PLT• Gr 3 hypertriglyceridemia-10.81011/1• Inability to receive at least ¾ doses of T
Citation Format: Anastasios Stathis, Felicitas Hitz, Urban Novak, Francesco Bertoni, Tatiana Terrot, Laura Moser, Ioanna Xenidou, Luca Mazzucchelli, Michele Ghielmini, Cristiana Sessa, Emanuele Zucca, Franco Cavalli. A phase I study of inotuzumab ozogamicin (IO) in combination with temsirolimus (T) in patients (pts) with relapsed or refractory (R/R) CD22-positive (pos) B-cell non-Hodgkin lymphomas (NHL). [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr CT402. doi:10.1158/1538-7445.AM2014-CT402