Background: We aimed to determine the safety and activity of the nintedanib+pembrolizumab combination. Nintedanib is an oral angiokinase inhibitor targeting the vascular endothelial, platelet-derived and fibroblast growth factor receptors as well as RET. Pembrolizumab is a highly selective, humanized monoclonal IgG4–kappa isotype antibody against PD-1 designed to block the negative immune regulatory signaling of the PD-1 receptor expressed by T cells. Methods: PEMBIB is a monocentric phase Ib trial which evaluated escalating doses of nintedanib (Dose level 1 (DL1) = 150 mg BID; DL2 = 200 mg BID) in combination with intravenous flat dose of pembrolizumab at 200 mg every 21 days in patients with advanced solid tumors using the rolling 6 design. A lead-in monotherapy of nintedanib was performed 7 days prior starting pembrolizumab. The primary objective was to establish MTD of this combination based on DLT occurrence during the first 4 weeks (28 days since C1D1) and to determine the recommended phase 2 dose (RP2D). Results: As of November 24, 2016, 13 patients (12 evaluable for DLT) have been enrolled in the escalation part : 2 cervical carcinoma, 1 MSI colorectal cancer, 1 triple negative breast cancer, 2 thymic carcinoma, 1 malignant pleural mesothelioma, 1 peritoneal mesothelioma, 1 gastric adenocarcinoma, 1 renal carcinoma, 1 neuroendocrine tumor, 1 nasopharyngeal cancer. The median age was 54, of these 50% were male, all ECOG 0 (83%) or 1. There were no grade 4-5 toxicities. The adverse events reported for more than 2 patients were alanine & aspartate aminotransferase increase, fatigue, anorexia, diarrhea, nausea, vomiting, hypothyroidism. Three dose-limiting toxicities of liver enzymes elevation were observed in 200 mg BID nintedanib thus recommending 150 mg BID nintedanib for the phase II part. Three patients have developed an objective RECIST partial response (ORR = 25%). Conclusions: Toxicity was consistent with the safety profile of each drug. Additional data for safety and efficacy is being further evaluated in the expansion part of this trial. The efficacy of the combination is currently further explored in 8 expansion cohorts of 30 patients. Clinical trial information: NCT02856425