EFFORT: Efficacy of AZD1775 in Parp Resistance; A Randomized 2-Arm, Non-Comparative Phase 2 Study of AZD1775 Alone or AZD1775 and Olaparib in Women With Ovarian Cancer Who Have Progressed During PARP Inhibition

Recurrent ovarian cancer with progression on or after prior PARP inhibitor

80 patients, median 4 prior therapies (1-11), 64% Pt-R, 48% BRCA MUT

Recurrence

ORR, DCR, DoR, PFS, evaluated per RECIST

Exploratory: BRCA status

A randomized two-arm non-comparative phase II
Ada (n=35): ORR: 23% (8PR); DoR: 5.5 months: DCR (4 months): 63% (8PR, 14SD); PFS: 5.5 months
Ada+Ola (n=35): ORR: 29% (10PR); DoR: 6.4 months: DCR (4 months): 89% (10PR, 21SD); PFS: 6.8 months

Exploratory analysis, BRCA status:
BRCA MUT:
Ada+Ola (n=16) vs Ada (n=15): ORR: 19 vs 20%; DoR: 6.4 vs 5.6 months; DCR (4 months): 81 vs 67%; PFS: 5.6 vs 5.6 months
BRCA WT:
Ada+Ola (n=18) vs Ada (n=16): ORR: 39 vs 31%; DoR: 8.7 vs 4.1 months; DCR (4 months): 94 vs 69%; PFS: 8.4 vs 4.1 months

Ada+Ola vs Ada:
Serious AE: none
Grade 3-4 AE: thrombocytopenia (20 vs 11%), neutropenia (14 vs 13%), diarrhea (12 vs 8%), fatigue (12 vs 3%), anemia (10 vs 3%)

Adavosertib alone and in combination with olaparib demonstrates efficacy in patients with PARPi-resistant ovarian cancer irrespective of BRCA status. Toxicities observed on both arms are generally manageable with supportive care, dose interruptions and dose reductions as needed.

Westin SN et al. EFFORT: EFFicacy Of adavosertib in parp ResisTance: A randomized two-arm non-comparative phase II study of adavosertib with or without olaparib in women with PARP-resistant ovarian cancer. J Clin Oncol (2021) 39 (suppl 15; abstr 5505)
https://meetinglibrary.asco.org/record/195547/abstract