Background: Poly(ADP-ribose) polymerase (PARP) enzymes are involved in DNA repair and activated by DNA strand breaks. DNA damage from carboplatin is associated with activation of PARP. Preclinical data indicate that PARP inhibition and trapping potentiates the anti-tumor effect of platinum chemotherapy. Talazoparib (T) is an oral, selective PARP inhibitor. This phase I study combines T with carboplatin (C) and paclitaxel (P). Methods: Two dosing schedules are being investigated. C is administered on day 1 and P on days 1, 8, and 15 of a 21-day cycle. T (100-1000mcg) is dosed once daily for days 1-7 (schedule A) or days 1-3 (schedule B). Dose escalation is by 3+3 design. Patients (pts) must have tumor type that is expected to respond to C + P or have BRCA germline or somatic mutation and adequate organ function. After 4-6 cycles of combination therapy, pts may continue the combination, change to C and intermittent T without P or change to T alone. Each schedule will have a 6 pt dose expansion at the MTD. The dose level (DL) 1 for schedule B is the previously reported MTD from schedule A (T 250mcg with C AUC 6 + P 80mg/m²). Results: Schedule B results are reported: 15 pts (median age 56 yrs [range 43-76]) have been enrolled. Primary malignancies include colorectal (4), pancreas (4), prostate (2), urothelial (2), and other (3). Dose was initiated at Schedule A MTD. DL2 (T 350mcg with C AUC 6 + P 80mg/m²) exceeded the MTD with 2 of 6 pts experiencing hematologic dose limiting toxicities (DLTs). DL1 is the confirmed schedule B MTD. Dose expansion to 6 pts is ongoing. Of the 11 pts with measurable disease, 3 (27%) had PR and 5 (45%) had SD. Pts were on study a median of 10 weeks (range 5-36+). Most common grade 3/4 AEs include leukopenia (53%), neutropenia (47%), and anemia (47%). One grade 5 AE of intracranial hemorrhage occurred, possibly related to therapy in the setting of grade 3 thrombocytopenia and concern for CNS disease. Conclusions: The schedule B MTD and RP2D is T 250 mcg with C AUC 6 and P 80mg/m². Data from the full dose expansion will be presented. This combination was tolerated with prolonged responses seen at lower dose T in combination with C+P. Clinical trial information: NCT02317874