Trial Outcomes & Findings for A Study to Investigate Efficacy and Safety With Oral AZD9833 Compared With Intramuscular Fulvestrant in Post-menopausal Women at Least 18 Years of Age With Advanced ER-positive HER2 Negative Breast Cancer (NCT NCT04214288)

Last Updated: 2025-11-20

Results Overview

PFS was assessed by the Investigator as defined by response evaluation criteria in solid tumors (RECIST) version 1.1. PFS was defined as the time from randomisation until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from randomised therapy or received another anti-cancer therapy prior to progression. Disease progression was defined as ≥20% increase in the sum of diameters of target lesions, unequivocal progression in non-target lesions, and/or appearance of new lesions. Data from the 300mg arm should be interpreted with caution as recruitment to the 300mg arm was stopped early at 20 patients randomised and therefore the 300mg data is highly variable.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE2

Target enrollment

240 participants

Primary outcome timeframe

From date of randomisation to date of objective disease progression (or last evaluable assessment in the absence of progression) or death (up to data cut-off of 29 months)

Results posted on

2025-11-20

Participant Flow

The patients were enrolled at 82 sites in 16 countries from 22 April 2020 to 30 August 2022. The study is ongoing.

Participant milestones

Participant milestones
Measure	AZD9833 75mg The patients received AZD9833 75mg oral tablets once daily.	AZD9833 150mg The patients received AZD9833 150mg oral tablets once daily.	AZD9833 300mg The patients received AZD9833 300mg oral tablets once daily.	Fulvestrant 500 mg The patients received Fulvestrant 500 mg via Intramuscular (IM) injection.
Overall Study STARTED	74	73	20	73
Overall Study COMPLETED	0	0	0	0
Overall Study NOT COMPLETED	74	73	20	73

Reasons for withdrawal

Reasons for withdrawal
Measure	AZD9833 75mg The patients received AZD9833 75mg oral tablets once daily.	AZD9833 150mg The patients received AZD9833 150mg oral tablets once daily.	AZD9833 300mg The patients received AZD9833 300mg oral tablets once daily.	Fulvestrant 500 mg The patients received Fulvestrant 500 mg via Intramuscular (IM) injection.
Overall Study Ongoing in the study	41	51	12	39
Overall Study Adverse Event	1	0	0	0
Overall Study Death	22	13	7	19
Overall Study Lost to Follow-up	1	2	1	0
Overall Study Other	1	2	0	6
Overall Study Protocol Violation	0	1	0	0
Overall Study Withdrawal by Subject	8	4	0	9

Baseline Characteristics

A Study to Investigate Efficacy and Safety With Oral AZD9833 Compared With Intramuscular Fulvestrant in Post-menopausal Women at Least 18 Years of Age With Advanced ER-positive HER2 Negative Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	AZD9833 75mg n=74 Participants The patients received AZD9833 75mg oral tablets once daily.	AZD9833 150mg n=73 Participants The patients received AZD9833 150mg oral tablets once daily.	AZD9833 300mg n=20 Participants The patients received AZD9833 300mg oral tablets once daily.	Fulvestrant 500 mg n=73 Participants The patients received Fulvestrant 500 mg via IM injection.	Total n=240 Participants Total of all reporting groups
Age, Continuous	61.2 Years STANDARD_DEVIATION 9.56	61.7 Years STANDARD_DEVIATION 9.68 • n=4 Participants	59.9 Years STANDARD_DEVIATION 10.72 • n=8 Participants	59.3 Years STANDARD_DEVIATION 11.08 • n=19 Participants	60.7 Years STANDARD_DEVIATION 10.16 • n=254 Participants
Sex: Female, Male Female	74 Participants	73 Participants n=4 Participants	20 Participants n=8 Participants	73 Participants n=19 Participants	240 Participants n=254 Participants
Sex: Female, Male Male	0 Participants	0 Participants n=4 Participants	0 Participants n=8 Participants	0 Participants n=19 Participants	0 Participants n=254 Participants
Race/Ethnicity, Customized Black or African American	0 Participants	0 Participants n=4 Participants	0 Participants n=8 Participants	2 Participants n=19 Participants	2 Participants n=254 Participants
Race/Ethnicity, Customized White	71 Participants	70 Participants n=4 Participants	20 Participants n=8 Participants	65 Participants n=19 Participants	226 Participants n=254 Participants
Race/Ethnicity, Customized Other	3 Participants	3 Participants n=4 Participants	0 Participants n=8 Participants	6 Participants n=19 Participants	12 Participants n=254 Participants

PRIMARY outcome

Timeframe: From date of randomisation to date of objective disease progression (or last evaluable assessment in the absence of progression) or death (up to data cut-off of 29 months)

Population: FAS consisted of all randomised patients, with treatment groups assigned in accordance with the randomisation, regardless of the actual treatment received.

Outcome measures

Outcome measures
Measure	AZD9833 75mg n=74 Participants The patients received AZD9833 75mg oral tablets once daily.	AZD9833 150mg n=73 Participants The patients received AZD9833 150mg oral tablets once daily.	AZD9833 300mg n=20 Participants The patients received AZD9833 300mg oral tablets once daily.	Fulvestrant 500 mg n=73 Participants The patients received Fulvestrant 500 mg via IM injection.
Progression-free Survival (PFS)	7.2 Months Interval 3.7 to 10.9	7.7 Months Interval 5.5 to 12.9	6.3 Months Interval 1.9 to The upper limit of 90% confidence interval (CI) was not estimable due to insufficient data.	3.7 Months Interval 2.0 to 6.0

SECONDARY outcome

Timeframe: From screening until disease progression (up to data cut-off of 29 months)

Population: A subset of the FAS with measurable disease.

ORR was assessed by the Investigator as defined by RECIST version 1.1. The ORR was defined as investigator assessed Complete Response or Partial Response prior to progression in patients with measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST v1.1). Adjusted response rate was presented in this analysis. Data from the 300mg arm should be interpreted with caution as recruitment to the 300mg arm was stopped early at 20 patients randomised and therefore the 300mg data is highly variable.

Outcome measures

Outcome measures
Measure	AZD9833 75mg n=70 Participants The patients received AZD9833 75mg oral tablets once daily.	AZD9833 150mg n=65 Participants The patients received AZD9833 150mg oral tablets once daily.	AZD9833 300mg n=19 Participants The patients received AZD9833 300mg oral tablets once daily.	Fulvestrant 500 mg n=68 Participants The patients received Fulvestrant 500 mg via IM injection.
Objective Response Rate (ORR)	15.7 Percentage (%)	17.1 Percentage (%)	25.2 Percentage (%)	11.6 Percentage (%)

SECONDARY outcome

Timeframe: From screening until disease progression or last evaluable assessment in the absence of progression (up to data cut-off of 29 months)

DoR was assessed by the Investigator as defined by RECIST version 1.1. The DoR was defined as the time from the date of first documented response until date of documented progression or death in the absence of disease progression.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At Week 16

The percentage change in tumour size at 16 weeks was obtained for each patient, based on RECIST measurements taken at baseline and at 16 weeks. Tumour size is the sum of the longest diameters of the target lesions (TLs). Percentage change in the sum of longest TLs diameters at 16 weeks was measured.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From the date of randomisation until death (up to data cut-off of 29 months)

The OS was defined as the time from randomisation to death due to any cause.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At Week 24

Population: FAS consisted of all randomised patients, with treatment groups assigned in accordance with the randomisation, regardless of the actual treatment received.

Clinical benefit rate was defined as patients with best objective response of complete response or partial response in the first 25 weeks or who have stable disease for at least 23 weeks after randomization. Adjusted response rate was presented in this analysis. Data from the 300mg arm should be interpreted with caution as recruitment to the 300mg arm was stopped early at 20 patients randomised and therefore the 300mg data is highly variable.

Outcome measures

Outcome measures
Measure	AZD9833 75mg n=74 Participants The patients received AZD9833 75mg oral tablets once daily.	AZD9833 150mg n=73 Participants The patients received AZD9833 150mg oral tablets once daily.	AZD9833 300mg n=20 Participants The patients received AZD9833 300mg oral tablets once daily.	Fulvestrant 500 mg n=73 Participants The patients received Fulvestrant 500 mg via IM injection.
Clinical Benefit Rate at 24 Weeks (CBR24)	48.8 Percentage (%)	51.0 Percentage (%)	42.4 Percentage (%)	39.1 Percentage (%)

SECONDARY outcome

Timeframe: Cycle 1 Day 15 (pre-dose), Cycle 1 Day 15 (2h), Cycle 1 Day 15 (4h) and Cycle 2 Day 1 (pre-dose), (each cycle is 28 days in length)

Population: The PK Analysis Set consisted of all patients who received at least one dose of AZD9833 per protocol, for whom there is at least one reportable PK concentration.

The plasma concentrations of AZD9833 at steady state were evaluated.

Outcome measures

Outcome measures
Measure	AZD9833 75mg n=69 Participants The patients received AZD9833 75mg oral tablets once daily.	AZD9833 150mg n=68 Participants The patients received AZD9833 150mg oral tablets once daily.	AZD9833 300mg n=19 Participants The patients received AZD9833 300mg oral tablets once daily.	Fulvestrant 500 mg The patients received Fulvestrant 500 mg via IM injection.
Plasma Concentrations of AZD9833 Cycle 2 Day 1 (pre-dose)	24.2895 ng/ml Geometric Coefficient of Variation 88.4140	34.2592 ng/ml Geometric Coefficient of Variation 245.9897	115.8558 ng/ml Geometric Coefficient of Variation 156.4858	—
Plasma Concentrations of AZD9833 Cycle 1 Day 15 (pre-dose)	22.8387 ng/ml Geometric Coefficient of Variation 84.3207	41.0856 ng/ml Geometric Coefficient of Variation 148.5806	108.1351 ng/ml Geometric Coefficient of Variation 157.3080	—
Plasma Concentrations of AZD9833 Cycle 1 Day 15 (2h)	51.9098 ng/ml Geometric Coefficient of Variation 94.4632	96.2038 ng/ml Geometric Coefficient of Variation 164.5328	302.1254 ng/ml Geometric Coefficient of Variation 66.9155	—
Plasma Concentrations of AZD9833 Cycle 1 Day 15 (4h)	54.5098 ng/ml Geometric Coefficient of Variation 87.2152	95.5360 ng/ml Geometric Coefficient of Variation 160.0032	289.1464 ng/ml Geometric Coefficient of Variation 68.1607	—

SECONDARY outcome

Timeframe: From baseline to Cycle 2 Day 1 (each cycle is 28 days in length)

The pharmacodynamics of AZD9833 and fulvestrant in a subgroup of patients.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From Day 1 until end of treatment and safety follow up (up to data cut-off of 29 months)

To evaluate the effect of AZD9833 and fulvestrant on the patients' health-related quality of life, as assessed by patient completed HRQoL questionnaires.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: From the date of first dose up to the safety follow-up period (28 days after last dose of AZD9833 and 56 days after last dose of fulvestrant) (up to data cut-off of 29 months)

Population: Safety analysis set consisted of all patients who received any amount of study treatment (AZD9833 or fulvestrant), regardless of whether that was the randomised therapy intended or whether they received therapy without being randomised and for whom any post-dose data are available.

The safety and tolerability of AZD9833 when compared to fulvestrant in women with advanced ER-positive HER2-negative breast cancer was evaluated.

Outcome measures

Outcome measures
Measure	AZD9833 75mg n=74 Participants The patients received AZD9833 75mg oral tablets once daily.	AZD9833 150mg n=73 Participants The patients received AZD9833 150mg oral tablets once daily.	AZD9833 300mg n=20 Participants The patients received AZD9833 300mg oral tablets once daily.	Fulvestrant 500 mg n=73 Participants The patients received Fulvestrant 500 mg via IM injection.
Number of Patients With Adverse Events Any AE causally related to treatment	39 Participants	49 Participants	14 Participants	13 Participants
Number of Patients With Adverse Events Any AE of CTCAE grade 3 or higher	9 Participants	17 Participants	3 Participants	11 Participants
Number of Patients With Adverse Events Any AE of CTCAE grade 3 or higher, causally related to treatment	1 Participants	2 Participants	1 Participants	0 Participants
Number of Patients With Adverse Events Any AE with outcome = death	0 Participants	1 Participants	0 Participants	0 Participants
Number of Patients With Adverse Events Any AE with outcome = death, causally related to treatment	0 Participants	0 Participants	0 Participants	0 Participants
Number of Patients With Adverse Events Any Serious Adverse Event (SAE)	6 Participants	7 Participants	2 Participants	4 Participants
Number of Patients With Adverse Events Any SAE, causally related to treatment	3 Participants	2 Participants	1 Participants	0 Participants
Number of Patients With Adverse Events Any SAE causing discontinuation of treatment	1 Participants	0 Participants	0 Participants	0 Participants
Number of Patients With Adverse Events Any SAE causing discontinuation of treatment, causally related to treatment	1 Participants	0 Participants	0 Participants	0 Participants
Number of Patients With Adverse Events Any AE leading to discontinuation of treatment	2 Participants	0 Participants	2 Participants	0 Participants
Number of Patients With Adverse Events Any AE leading to discontinuation of treatment, causally related to treatment	2 Participants	0 Participants	0 Participants	0 Participants
Number of Patients With Adverse Events Any AE leading to dose reduction	1 Participants	9 Participants	4 Participants	0 Participants
Number of Patients With Adverse Events Any AE leading to dose interruption	11 Participants	16 Participants	4 Participants	3 Participants
Number of Patients With Adverse Events Any Adverse Event (AE)	57 Participants	66 Participants	19 Participants	50 Participants

Adverse Events

AZD9833 75mg

Serious events: 6 serious events

Other events: 44 other events

Deaths: 23 deaths

AZD9833 150mg

Serious events: 7 serious events

Other events: 61 other events

Deaths: 14 deaths

AZD9833 300mg

Serious events: 2 serious events

Other events: 17 other events

Deaths: 7 deaths

Fulvestrant 500 mg

Serious events: 4 serious events

Other events: 31 other events

Deaths: 21 deaths

Serious adverse events

Other adverse events

Additional Information

Global Clinical Lead

AstraZeneca

Phone: 1-877-240-9479

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER