Phase I/II Study of the Anti-Programmed Death Ligand-1 Antibody 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

Trial ID # NCT02484404
Phase I/II
Drug Class DNA Damage Repair Pathway Inhibitors: PARP
Drug Name Olaparib
Alternate Drug Names AZD2281, Lynparza
Drugs in Trial Cediranib, Durvalumab, Olaparib
Eligible Participant

Advanced or recurrent ovarian cancer refractory to standard treatment

Patients Enrolled

318 [Phase I: Ola+Ced+Dur: 7; Phase II: Ola+Dur: 35, median of 3.5 prior therapies (1-16)]

Therapy Setting

Recurrence

Study Design

Open-Label, Non-randomized

Endpoints

ORR, DCR, RP2D, evaluated per RECIST

Biomarkers

Exploratory: PD-L1 protein

Efficacy

Ola+Dur:
RP2D: 300mg Ola bid+1500mg Dur q28d
Phase 2 results:
ORR: 15% (5PR, n=34); DCR (4 months): 53% (5PR, 13SD, n=34) (86% Pt-R, 83% BRCA WT)
Phase I results:
Ola+Ced+Dur:
RP2D: 300mg Ola bid +1500mg Dur q28d + 20 mg Ced 5 days on/2 days off
ORR: 29% (2PR, n=7)

Clinically Significant Adverse Events

Ola+Dur:
Serious AE: none
Grade 3-4 AE: lymphopenia (25%), anemia (8%)
Ola+Ced+Dur:
Serious AE: none
Grade 3-4 AE: lymphopenia (11%), anemia (11%), hypertension (11%)

Conclusion

Promising response rates for olaparib, cediranib and durvalumab combinations independent of PD-L1 expression levels

Reference

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 A et al. A phase I study of durvalumab (D) in combination with olaparib (O) and cediranib (C) in recurrent women’s cancers. Ann Oncol (2017) 28 (suppl_5): v122-v141. 10.1093/annonc/mdx367
http://oncologypro.esmo.org/Meeting-Resources/ESMO-2017-Congress/A-phase-I-study-of-durvalumab-D-in-combination-with-olaparib-O-and-cediranib-C-in-recurrent-women-s-cancers

Lee J-M et al. A phase II study of durvalumab, a PD-L1 inhibitor and olaparib in recurrent ovarian cancer (OvCa) Ann Oncol (2018) 29 (suppl_8 abstr 936PD)
https://academic.oup.com/annonc/article/29/suppl_8/mdy285.145/5141748