Phase I/II Study of the Anti-Programmed Death Ligand-1 Antibody Durvalumab (MEDI4736) in Combination With Olaparib and/or Cediranib for Advanced Solid Tumors and Advanced or Recurrent Ovarian, Triple Negative Breast, Lung, Prostate and Colorectal Cancers

Advanced or recurrent ovarian cancer refractory to standard treatment

318 [ovarian: Phase I: Ced+Dur: 9 (4 Pt-S, 5 Pt-R); Ced+Dur+Ola: 7 (2 Pt-S, 5 Pt-R)]

Recurrence

Open-Label, Non-randomized

ORR, DCR, DoR, RP2D, evaluated per RECIST

Exploratory: PD-L1 protein

Ced+Dur:
RP2D: 1500mg Dur q28d +20 mg Ced 5 days on/2 days off
ORR: 42.9% (3PR, n=7) (3 Pt-S)
DCR (4 months): 71.4% (3PR, 2SD, n=7) (4Pt-S, 1 Pt-R)

Ced+Dur+Ola:
RP2D: 1500mg Dur q28d + 300mg Ola bid + 20 mg Ced 5 days on/2 days off
ORR: 42.9% (3PR, n=7)(1 Pt-S BRCA MUT, 2 Pt-R BRCA WT)
DCR: 71.4% (3PR, 2SD, n=7) (2 Pt-R BRCA WT w/ SD for 19, 21 months)
DoR: 8.5 months

Ced+Dur:
Serious AE: none
Grade 3-4 AE: hypertension (17%), fatigue (17%)
Ced+Dur+Ola:
Serious AE: none
Grade 3-4 AE: lymphopenia (11%), anemia (11%), hypertension (11%)

Promising response rates for cediranib, durvalumab and olaparib combinations

Lee, J-M et al. Safety and Clinical Activity of the Programmed Death-Ligand 1 Inhibitor Durvalumab in Combination With Poly (ADP-Ribose) Polymerase Inhibitor Olaparib or Vascular Endothelial Growth Factor Receptor 1-3 Inhibitor Cediranib in Women's Cancers: A Dose-Escalation, Phase I Study. J Clin Oncol (2017) 35(19):2193-2202
https://www.ncbi.nlm.nih.gov/pubmed/28471727

Zimmer AS et al. A phase I study of the PD-L1 inhibitor, durvalumab, in combination with a PARP inhibitor, olaparib, and a VEGFR1-3 inhibitor, cediranib, in recurrent women's cancers with biomarker analyses. J Immunther Cancer (2019) 7(1):197
https://www.ncbi.nlm.nih.gov/pubmed/31345267