Background: Pazopanib, an anti-angiogenic tyrosine kinase inhibitor, has shown activity in pre-treated advanced glioblastomas. A clinical-biological rationale defends the evaluation of the activity of Pazopanib in earlier stage of the disease. Methods: Pazoglio (NCT02331498) is a phase I/II, prospective, multicenter, open-label trial to evaluate the safety and efficacy of Pazopanib combined with temozolomide (TMZ) during the maintenance phase as defined by the Stupp protocol in patients with resected glioblastoma. We report the dose escalation phase I (standard 3+3) whose main objective is to determine the MTD and the RP2D of Pazopanib combined with TMZ during the maintenance phase. The DLT was assessed during the first two cycles. Pazopanib was dosed according to four levels: 200 mg (level 1), 400 mg (level 2), 600 mg (level 3) and 800 mg (level 4). Results: From September 2015 to March 2022, 42 patients (pts) were recorded, and 20 pts finally enrolled. Median age was 54 years [min: 25 – max: 69], 14/20 were women, 15/20 had a complete resection. No DLT was observed among the six patients of levels 1 and 2. One DLT was recorded among the three first pts of the level 3 (grade 2 thrombopenia leading to a postponement of the pazopanib of more than 7 days) but this pt was wrongly enrolled and finally not evaluable for DLT. Three additional pts were enrolled in the level 3 and no DLT was recorded. No DLT was recorded in the 3 first pts of the level 4 but the occurrence of a grade 2 thrombopenia lasting more than 7 days and leading to the cancelation of the third cycle of TMZ in the first pt, as well as a grade 3 thrombopenia and grade 3 neutropenia leading to the postponement and decrease of the dosage of the second cycle of TMZ for the third pt, lead to the enrollment of 3 additional pts in the level 3 according to the IDMC recommendation. One DLT was recorded (grade 2 thrombopenia leading to a postponement of the pazopanib of more than 7 days). Overall, one DLT was observed among the 8 evaluable pts of the level 3. Three additional pts were enrolled in the level 4. Overall, two DLT were recorded among the 6 patients enrolled in the level 4: one grade 3 thrombopenia (postponement and decrease of Pazopanib and TMZ dosage) and one grade 3 hypertension (decrease of Pazopanib dosage). Overall, 328 Adverse Events were recorded during the 6 cycles of treatment, most of which being Grade1-2 (hypertension, increase ALT, asthenia, nausea, diarrhea, thrombopenia, neutropenia, anemia). No grade 4 or 5 AE was observed. The RP2D is 600 mg daily pazopanib in combination with TMZ, RP2D was hardly established since several adaptations of dose intensity, not formerly defined as DLT, were recorded during the 6 cycles of maintenance treatment. Conclusions: The addition of Pazopanib to TMZ during the maintenance part of the “Stupp protocol” is feasible in resected and fit glioblastoma pts. The phase II part of Pazoglio is currently enrolling. Clinical trial information: NCT02331498.