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 Lynparza, AZD2281
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 (2 Pt-S, 5 Pt-R); 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, DoR, 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:
ORR: 42.9% (3PR, n=7)(1 Pt-S BRCA MUT, 2 Pt-R BRCA WT)
DCR: 71.4% (3PR, 2SD, n=17) (2 Pt-R BRCA WT w/ SD for 19, 21 months)
DoR: 8.5 months

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

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

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

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