Background: P is a tyrosine kinase inhibitor of PDGFR, VEGFR and KIT. This study aimed to determine the recommended phase II dose (RP2D) of P combined with I. To assess the impact of scheduling on tolerability, two I schedules were explored. Methods: Pts with progressive ST, no standard therapy available, PS 0-1 and good organ function were eligible. Pts received daily P with 3-weekly I, 9 g/m²/cycle, either continuously (Iciv) or as 3 hrs boluses (Ibolus) for 3 days. P was escalated in serial cohorts of 3-9 pts per I-schedule. If in 3-6 pts dose-limiting toxicity (DLT) of 33.3% within 1^st cycle was seen 3 more pts at that dose level (DL) were enrolled. RP2D was exceeded if in > 1/3 pts, > 2/6 pts or ≥ 3/9 pts DLT occurred. P was maximized at 1000 mg/day. At RP2D, an expansion cohort of 6-9 pts was studied to confirm safety. PK samples of P and I were collected in all pts. Sampling allowed intra-individual comparison of I-PK with or without P and vice versa. Results: 47 pts were studied. For Iciv (25 pts), RP2D was the maximum dose of P (1000 mg), higher than the single agent RP2D. At RP2D 2 DLTs in 15 pts occurred: 1 febrile neutropenia (FN); 1 encephalopathy. With Ibolus (22 pts), P 400 mg with or without GCSF was not tolerated (5 DLTs in 10 pts: 3*FN, 1 encephalopathy; 1 proteinuria). At RP2D (P 200 mg + Ibolus + GCSF) 3 DLTs in 12 pts (FN; encephalopathy, renal insufficiency) were observed. Toxicity occurring in >30% of pts in Iciv (all grades/grade 3-4,%) were neutropenia (92/92) anemia (92/8); thrombocytopenia (35/12), elevated ASAT, ALAT, alkaline phosphatase (73/4; 73/0; 62/2), nausea (58/0), vomiting (73/0), diarrhea (54/0) and hypertension (31/12). 4/25 pts in Iciv evaluable for response had PR (2 sarcoma, 2 ovary) and 10 prolonged (≥3 mths) SD. In Ibolus, 6/20 pts had PR (2 urothelial, 1 sarcoma, 1 ovary, 1 CUP, 1 mesothelioma) and 3/20 prolonged SD. Preliminary PK analysis showed no effect of P on I-exposure, neither of Ibolus or Iciv on P. Conclusions: P is tolerated at a higher dose combined with Iciv compared to Ibolus (1000 vs 200 mg). PK cannot explain this difference. This study underlines the impact of scheduling on the tolerability of VEGFR-TKI and cytotoxic drug combinations.