Background: The PARP-inhibitor olaparib has single-agent activity in BRCA mutated breast and ovarian cancer. Preclinical studies show synergistic effects when combining PARP-inhibitors and platinum drugs in BRCA1/2 mutated cancer cell models. A formulation change from olaparib capsules to tablets initiated a new dose finding study of olaparib tablets BID continuously with carboplatin. Methods: Patients were included in a 3+3 dose-escalation schedule in the following dose-levels: olaparib 25mg BID and carboplatin AUC 3 d1/d22, olaparib 25mg BID and carboplatin AUC 4 d1/d22, olaparib 50mg BID and carboplatin AUC4 d1/d22, olaparib 75mg and carboplatin AUC 4 d1/d22 and olaparib 100mg BID and carboplatin AUC 4 d1/d22. After two cycles patients continued olaparib 300mg BID as monotherapy. Primary objective was to assess the Maximum Tolerable Dose (MTD). Secondary objectives were to investigate the preliminary response rate, pharmacodynamics and systemic exposure. Results: In total 24 patients were included with breast cancer (n = 18), ovarian cancer (n = 3), melanoma (n = 1), colorectal cancer (n = 1) and esophageal cancer (n = 1). Nineteen out of 24 patients had a germline BRCA mutation (79%). Most common AEs were nausea (46%), fatigue (33%) and platelet count decrease (33%). The majority of AEs (83%) were grade 1/2 in severity. Because two dose-limiting toxicities (consisting of ≥ 7 days dose delay of cycle 2 or missing ≥ 5 doses of olaparib due to hematologic toxicity) occurred in dose-level 4, dose-level 3 (olaparib 75mg and carboplatin AUC 4; n = 6 patients) was determined to be the MTD. Fourteen out of 24 patients (56%) had a partial response as best response, according to RECIST 1.1. Systemic exposure of the olaparib tablet formulation appeared comparable to the previous capsule formulation with an olaparib tablet AUC_0-14 of 16.3 μg/ml*h at MTD. PARP activity in PBMCs was decreased by 98.7% ± 0.14% at day eight compared to day one for dose-level 3. Conclusions: Olaparib tablets 75mg BID and carboplatin AUC 4 for two cycles preceding olaparib monotherapy is a feasible and tolerable treatment schedule with encouraging clinical antitumor activity. Clinical trial information: NCT02418624