Background: Le is a thalidomide analogue with both immunomodulatory and anti-angiogenic properties. Le has shown efficacy and good tolerability as single agent for LROC pts (Selle F, et al. Ann Oncology 2014). Methods: LROC pts were enrolled in cohorts of 3 to 6 pts and treated with PLD 30 mg/m2 and C AUC 5 day (d)1 q4 weeks in combination with daily oral escalation dose of Le (15, 20 and 25 mg/d) according to different schedules (A: 21 consecutive days from d1; B: 21d from d2; C: 21d from d7; D: 14d from d2). Dose limiting toxicities (DLT) were defined as: treatment delay ( > 14d), grade (Gr) 3 febrile neutropenia, Gr 4 neutropenia or Gr 4 thrombocytopenia lasting more than 7 d, bleeding with platelet transfusion and all other Gr ≥ 3 toxicity (except vomiting) occurring at cycle 1. Completion of the 6 planned cycles without inacceptable toxicity defined feasibility of the regimen. Secondary objectives were response, progression-free (PFS) and overall survival (OS) rates. Results: 22 pts were enrolled up to 01/2014 with a median age of 61.4 years (47-73). Pts characteristics were: serous (82%), previous lines (one 68%, two 32%), median platinum-free interval (PFI) 11.4 months and ECOG 0 (73%). Safety: all the 4 schedules were evaluated at a 15mg/d Le dose. With schedule A&B, 2DLT/3pts and 3DLT/4pts were observed. DLT was cycle delay > 14d for neutropenia (2pts) or neurotoxicity (1pt), Gr3 thrombosis (1pt) and Gr3 visual acuity decreased (1pt). With schedule C&D, 1DLT/9pts (Gr3 rash) occurred at cycle 1, only 1 pt completed the 6 planned cycles without dose reduction and 6 pts stopped early for toxicity (hematotoxicity for 5pts). Efficacy: complete and partial responses were observed in respectively 10% and 29% of pts. Median PFS and OS were 9.2 months (95% CI, 7.4-11) 28 months (95% CI, 18.9-37.1) respectively. Conclusions: Lenalidomide combined with PLD-C was not feasible at the dose and schedules evaluated, mainly due to cumulative hematologic toxicity. Clinical trial information: NCT01111903