Purpose Data suggest that DNA damage by poly (ADP-ribose) polymerase inhibition 
and/or reduced vascular endothelial growth factor signaling by vascular 
endothelial growth factor receptor inhibition may complement antitumor activity 
of immune checkpoint blockade. We hypothesize the programmed death-ligand 1 
(PD-L1) inhibitor, durvalumab, olaparib, or cediranib combinations are tolerable 
and active in recurrent women's cancers. Patients and Methods This phase I study 
tested durvalumab doublets in parallel 3 + 3 dose escalations. Durvalumab was 
administered at 10 mg/kg every 2 weeks or 1,500 mg every 4 weeks with either 
olaparib tablets twice daily or cediranib on two schedules. The primary end 
point was the recommended phase II dose (RP2D). Response rate and 
pharmacokinetic analysis were secondary end points. Results Between June 2015 
and May 2016, 26 women were enrolled. The RP2D was durvalumab 1,500 mg every 4 
weeks with olaparib 300 mg twice a day, or cediranib 20 mg, 5 days on/2 days 
off. No dose-limiting toxicity was recorded with durvalumab plus olaparib. The 
cediranib intermittent schedule (n = 6) was examined because of recurrent grade 
2 and non-dose-limiting toxicity grade 3 and 4 adverse events (AEs) on the daily 
schedule (n = 8). Treatment-emergent AEs included hypertension (two of eight), 
diarrhea (two of eight), pulmonary embolism (two of eight), pulmonary 
hypertension (one of eight), and lymphopenia (one of eight). Durvalumab plus 
intermittent cediranib grade 3 and 4 AEs were hypertension (one of six) and 
fatigue (one of six). Exposure to durvalumab increased cediranib area under the 
curve and maximum plasma concentration on the daily, but not intermittent, 
schedules. Two partial responses (≥15 months and ≥ 11 months) and eight stable 
diseases ≥ 4 months (median, 8 months [4 to 14.5 months]) were seen in patients 
who received durvalumab plus olaparib, yielding an 83% disease control rate. Six 
partial responses (≥ 5 to ≥ 8 months) and three stable diseases ≥ 4 months (4 to 
≥ 8 months) were seen in 12 evaluable patients who received durvalumab plus 
cediranib, for a 50% response rate and a 75% disease control rate. Response to 
therapy was independent of PD-L1 expression. Conclusion To our knowledge, this 
is the first reported anti-PD-L1 plus olaparib or cediranib combination therapy. 
The RP2Ds of durvalumab plus olaparib and durvalumab plus intermittent cediranib 
are tolerable and active. Phase II studies with biomarker evaluation are 
ongoing.