This Phase 2b study aims to evaluate the efficacy and safety of adavosertib, an inhibitor of the tyrosine kinase WEE1, in subjects with recurrent or persistent uterine serous carcinoma (USC) who have previously received at least 1 prior platinum-based chemotherapy regimen for the management of USC.
This Phase 2b, open-label, single-arm, multi-center study will assess the efficacy and safety of adavosertib in eligible subjects with histologically confirmed recurrent or persistent USC, evidence of measurable disease as per Response Evaluation Criteria in Solid Tumors.(RECIST) v1.1, and who have received at least 1 prior platinum-based chemotherapy regimen for the management of USC. Subjects with carcinosarcomas are not eligible.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
109
The subjects will receive oral adavosertib 300 mg, once daily on Days 1 to 5 and Days 8 to 12 of a 21-day treatment cycle.
Research Site
Burbank, California, United States
Objective Response Rate (ORR)
Per Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 for target lesions (TLs) and assessed by computed tomography (CT) or magnetic resonance imaging (MRI): Complete response (CR), Disappearance of all target lesions; Partial response (PR), \>=30% decrease in the sum of the diameters of TL, taking as reference the baseline sum of diameters.
Time frame: up to 75 weeks
Duration of Response (DoR)
The time from the date of first documented response until date of documented progression per RECIST v1.1 as assessed by BICR, or death in the absence of disease progression
Time frame: up to 75 weeks
Depth of Response
Depth of response is defined as best percentage change from baseline in target lesion size, which is the maximum reduction from baseline or the minimum increase from baseline in the absence of a reduction. A negative change denotes a reduction in target lesion size.
Time frame: Up to 75 weeks
Progression Free Survival (PFS)
The time from first dose until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the participant withdraws from study drug or receives another anticancer therapy prior to progression. PFS was assessed per RECIST v1.1 using CT or MRI scans by BICR.
Time frame: Up to 75 weeks
Progression Free Survival Rate at 6 Months (PFS6)
The progression free survival rate was assessed at 6 months by Kaplan-Meier estimate per RECIST v1.1.
Time frame: Up to 6 months
Overall Survival (OS)
The time from date of first dose until the date of death due to any cause
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Research Site
Duarte, California, United States
Research Site
La Jolla, California, United States
Research Site
West Hollywood, California, United States
Research Site
Aurora, Colorado, United States
Research Site
Iowa City, Iowa, United States
Research Site
Covington, Louisiana, United States
Research Site
Boston, Massachusetts, United States
Research Site
Rochester, Minnesota, United States
Research Site
New Brunswick, New Jersey, United States
...and 17 more locations
Time frame: Up to 75 weeks
Disease Control Rate (DCR)
The percentage of participants who have a best overall response of confirmed response (CR) or partial response (PR) or who have stable disease for at least 5 weeks after start of treatment, based on BICR.
Time frame: Up to 75 weeks
Lowest Concentration (Ctrough) of Adavosertib
Lowest plasma concentration of adavosertib was evaluated as pharmacokinetic paramerter.
Time frame: Cycle 1, Day 5 and Cycle 2, Day 5 (pre-dose) (each cycle is 21 days)
Maximum Concentration (Cmax) of Adavosertib
Maximum plasma concentration of adavosertib was evaluated as pharmacokinetic parameter.
Time frame: Cycle 1, Day 5 and Cycle 2, Day 5 (2 hours post-dose) (each cycle is 21 days)
Number of Participants With Treatment Emergent Adverse Events (AEs)
The number of participants with treatment emergent adverse events (AEs) were assessed as variable of safety and tolerability. The adverse events reported here were treatment emergent.
Time frame: From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks