A Phase Ib, Open-Label, Multi-Centre Study to Assess the Safety, Tolerability, Pharmacokinetics, and Anti-tumour Activity of AZD1775 Monotherapy in Patients With Advanced Solid Tumours

Trial ID #	NCT02482311
Phase	Ib
Drug Class	Cell Cycle Inhibitors: WEE1
Drug Name	Adavosertib
Alternate Drug Names	WEE1 inhibitor AZD1775, MK1775, AZD1775
Drugs in Trial	Adavosertib
Eligible Participant	Advanced solid tumors (with expansions in BRCA1/2 MUT ovarian cancer after PARPi-failure and BRCA WT ovarian cancer)
Patients Enrolled	80 (30 BRCA1/2 MUT ovarian cancer after PARPi-failure, median 6 prior therapies; 16 BRCA WT ovarian cancer, median 7 prior therapies)
Therapy Setting	Recurrence
Study Design	Open-Label, Non-randomized
Endpoints	ORR, DCR, PFS, evaluated per RECIST
Biomarkers	BRCA1/2
Efficacy	Adavosertib (175 mg PO bid) on days 1–3 and 8–10 per 21-day cycle BRCA MUT after PARPi failure (n=30): ORR: 3.3% (1PR); DCR: 77% (1PR, 22SD) - 1 patient with SD had CCNE1 AMP (no other patients with CCNE1 AMP) PFS: 3.9 months BRCA WT (n=16): ORR: 6.3% (1PR); DCR: 69% (1PR, 10SD) - patient with PR had CCNE1 AMP (no other patients with CCNE1 AMP) PFS: 4.5 months
Clinically Significant Adverse Events	Serious AE: 1 death Grade 3-4AE:
Conclusion	Adavosertib was well tolerated and showed preliminary antitumor activity. No clear correlation between genomic profile and clinical response was observed
Reference	Bauer TM et al. A Phase Ib Study Assessing the Safety, Tolerability, and Efficacy of the First-in-Class Wee1 Inhibitor Adavosertib (AZD1775) as Monotherapy in Patients with Advanced Solid Tumors. Target Oncol (2023) 18(4):517-530 https://pubmed.ncbi.nlm.nih.gov/37278879/