Phase II Pharmacological Study With Wee-1 Inhibitor MK-1775 Combined With Carboplatin in Patients With p53 Mutated Epithelial Ovarian Cancer and Early Relapse (< 3 Months) or Progression During Standard First Line Treatment

Trial ID # NCT01164995
Phase II
Drug Class Cell Cycle Inhibitors: Wee1
Drug Name Adavosertib
Alternate Drug Names WEE1 inhibitor AZD1775, MK1775, AZD1775
Drugs in Trial Adavosertib, Carboplatin
Eligible Participant

TP53-mutated ovarian cancer refractory or resistant to first-line carboplatin plus paclitaxel

Patients Enrolled

24

Therapy Setting

Recurrence

Study Design

Open-Label, Non-randomized

Endpoints

ORR, PFS, OS, evaluated per RECIST

Biomarkers

TP53 MUT

Efficacy

ORR: 43% (1CR, 8PR, n=21)
PFS: 5.3 months (2.3-9.0)
OS: 12.6 months (4.9-19.7)

Exploratory analysis Pt status:
Pt-R: ORR: 62% (1CR, 7PR, n=13)
Pt-Rf: ORR: 13% (1PR, n=8)

Clinically Significant Adverse Events

Serious AE: none
Grade 3-4 AE: thrombocytopenia (48%), neutropenia (39%), anemia (9%)

Conclusion

Promising activity in TP53-mutated primary platinum-resistant and platinum-refractory patients

Reference

Leijen S et al. Phase II Study of WEE1 Inhibitor AZD1775 Plus Carboplatin in Patients With TP53-Mutated Ovarian Cancer Refractory or Resistant to First-Line Therapy Within 3 Months. J Clin Oncol (2016) 34(36):4354-4361
https://www.ncbi.nlm.nih.gov/pubmed/27998224