Background: Immune checkpoint blockade has shown clinical activity in subsets of advanced solid tumors. O and C have single agent activity in recurrent ovarian cancer (OvCa). We hypothesize O and C will complement the antitumor activity of D by increasing DNA damage through repair inhibition and hypoxia induction. This phase I study evaluated the safety and preliminary activity of the combinations of D+O and D+C. Methods: Eligible pts with PS 0-1 and good end organ function received D+O or D+C in parallel dose escalations in a 3+3 design. D+O included O tablets (200 or 300 mg bid) with D 10 mg/kg IV every 14d (dose level [DL] 1, 2) and O 300 mg bid with D 1500 mg IV every 28d (DL3). D+C tested C 20 or 30 mg daily with D 10 mg/kg IV every 14d (DL1, 2). The DLT period was one 28d cycle. Safety was assessed by CTCAEv4.0 and response by RECISTv1.1. Results: 19 pts (median age 66 [39-70], median 4 prior therapies [2-7]) were treated. D+O includes 10 OvCa and 2 triple negative breast Ca pts. D+C had 4 OvCa, 2 cervical Ca and 1 uterine leiomyosarcoma pts. The MTD for D+O is DL3. Gr3/4 D+O adverse events (AEs) include lymphopenia (2/12) and anemia (1/12). D+C gr3/4 AEs include hypertension (2/7), diarrhea (2/7), pulmonary embolism (2/7), pulmonary hypertension (1/7), and lymphopenia (1/7). 2 D+C DL1 pts required early discontinuation of C for pulmonary embolism and 1 pt on DL1 had C dose reduction due to recurrent gr2 fatigue and abdominal pain on cycle 2. 4 D+C DL2 pts had dose reduction on cycles 2 or 3 due to recurrent gr2 fatigue, abdominal pain and/or dyspnea. 1 PR (6⁺ mo) and 5 SD ≥ 4 mo (56%; [4-6⁺]) were seen in 9 evaluable D+O pts, yielding a 67% disease control rate (DCR). All were BRCA wild type. 2 PR (5, 4⁺ mo) and 2 SD ≥ 4 mo (4⁺ mo) were seen in 7 evaluable D+C pts, for a 57% DCR. Archival tissue samples for PD endpoints including PD-L1 expression and blood for PK are under analysis. Conclusions: The RP2D for D+O (O tablets 300 mg bid with M 1500 mg q28d) is tolerable and active in OvCa and TNBC pts without germline BRCA mutation. New D+C DLs will examine an intermittent C schedule with D 1500 mg every 28d. Phase II expansion studies of D+O in OvCa, TNBC, lung, and prostate cancers are now open to accrual. Clinical trial information: NCT02484404