A Phase Ib Study of AZD1775 and Olaparib in Patients With Refractory Solid Tumours

Trial ID # NCT02511795
Phase Ib
Drug Class Cell Cycle Inhibitors: WEE1
Drug Name Adavosertib
Alternate Drug Names WEE1 inhibitor AZD1775, MK1775, AZD1775
Drugs in Trial Adavosertib, Olaparib
Eligible Participant

Recurrent ovarian cancer (no prior PARP inhibitor)

Patients Enrolled

119 (26 ovarian)

Therapy Setting

Recurrence

Study Design

Open-Label, Non-randomized

Endpoints

ORR, DCR, evaluated per RECIST

Efficacy

RP2D once daily (qd) dosing: adavosertib 200 mg qd 3/4 days for 2/3 weeks+olaparib 200 mg bid
RP2D twice daily (bid) dosing: adavosertib 150 mg bid 3/4 days for 2/3 weeks+olaparib 200 mg bid

26 ovarian w/ adavosertib qd or bid dosing:

ORR: 15% (3PR - 1 BRCA MUT, n=20)
DCR: 85% (3PR - 1 BRCA MUT, 15SD - 1 BRCA MUT, n=20)

1 ovarian at qd RP2D dosing: 1SD
4 ovarian at bid RP2D dosing: 2PR, 2SD (2SD w/ CCNE1 AMP)

Clinically Significant Adverse Events

Serious AE: 1 sepsis
Grade 3-4 AE: all (61.3%), anemia (23.5%), neutropenia (21.8%), thrombocytopenia (16.8%)

Conclusion

Adavosertib+olaparib shows antitumor activity, particularly at the twice daily (BID) schedule

Reference

Hamilton E et al. Phase Ib study of adavosertib in combination with olaparib in patients with refractory solid tumors: Dose escalation. Cancer Res (2019) 79(13 Suppl):abstr CT025
http://cancerres.aacrjournals.org/content/79/13_Supplement/CT025

Hamilton E et al. Phase Ib study of adavosertib in combination with olaparib in patients with refractory solid tumors: Dose escalation. Poster
https://www.clearityfoundation.org/wp-content/uploads/2020/01/NCT02511795-AACR-2019-poster.pdf

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