Efficacy and safety study of olaparib in combination with paclitaxel to treat advanced gastric cancer.

Study identifier:D081BC00004

ClinicalTrials.gov identifier:NCT01924533

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

A randomized, double-blinded, placebo controlled, multicentre phase III study to assess the efficacy and safety of olaparib (AZD2281) in combination with paclitaxel, compared to placebo in combination with paclitaxel, in Asian patients with advanced gastric cancer (including the gastro-oesophageal junction) who have progressed following first line therapy

Medical condition

gastric cancer

Phase

Phase 3

Healthy volunteers

Study drug

Olaparib, Paclitaxel, Placebo

Sex

All

Actual Enrollment

525

Study type

Interventional

Age

18 Years - 99 Years

Date

Study Start Date: 03 Sept 2013

Primary Completion Date: 04 Apr 2016

Study Completion Date: 27 Mar 2023

Study design

Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind
Primary Purpose: Treatment

Verification:

Verified 01 Mar 2024 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

Location

Research Site

Seongnam-si, Republic of Korea, 13620

Location

Research Site

Sapporo-shi, Japan, 003-0804

Location

Research Site

Kasama-shi, Japan, 309-1793

Location

Research Site

Chiba-shi, Japan, 260-8717

Location

Research Site

Chuo-ku, Japan, 104-0045

Location

Research Site

Koto-ku, Japan, 135-8550

Location

Research Site

Nagoya-shi, Japan, 464-8681

Location

Research Site

Takatsuki-shi, Japan, 569-8686

Arms	Assigned Interventions
Experimental: Olaparib+ paclitaxel olaparib + paclitaxel	Drug: Olaparib Tablets-at a dose of 100mg orally twice daily, throughout each cycle (28 days); Once paclitaxel dosing is stopped, the planned monotherapy olaparib dose will be 300mg twice daily. Drug: Paclitaxel IV infusion over 1 hour at 80 mg/m2 weekly on days 1, 8 and 15 of a 28 days schedule.
Placebo Comparator: Placebo+paclitaxel placebo+ paclitaxel	Drug: Paclitaxel IV infusion over 1 hour at 80 mg/m2 weekly on days 1, 8 and 15 of a 28 days schedule. Drug: Placebo Tablets-at a dose of 100mg orally twice daily, throughout each cycle (28 days); Once paclitaxel dosing is stopped, the planned monotherapy placebo dose will be 300mg twice daily.

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
The number of participants in the participant flow (525) includes all participants who were eligible and assigiend to each treatment group.

Reporting Groups

	Description
Olaparib 100 mg tablets bd + Paclitaxel 80 mg/m^2	Olaparib 100 mg tablets bd + Paclitaxel 80 mg/m^2
Placebo tablets bd + Paclitaxel 80 mg/m^2	Placebo tablets bd + Paclitaxel 80 mg/m^2

Participant Flow: Overall Study

	Olaparib 100 mg tablets bd + Paclitaxel 80 mg/m^2	Placebo tablets bd + Paclitaxel 80 mg/m^2
STARTED	263	262
COMPLETED	74	57
NOT COMPLETED	189	205
Death	181	200
Lost to Follow-up	0	1
Withdrawal by Subject	7	3
Other Eligibility criteria	1	1

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

Reporting Groups

	Description
Olaparib 100 mg tablets bd + Paclitaxel 80 mg/m^2	Olaparib 100 mg tablets bd + Paclitaxel 80 mg/m^2
Placebo tablets bd + Paclitaxel 80 mg/m^2	Placebo tablets bd + Paclitaxel 80 mg/m^2

Baseline Measures

	Olaparib 100 mg tablets bd + Paclitaxel 80 mg/m^2	Placebo tablets bd + Paclitaxel 80 mg/m^2	Total
Number of Participants [units: Participants]	263	262	525
Age Continuous [units: Years] Mean ± Standard Deviation	57.1 ± 11.90	57.3 ± 11.14	57.2 ± 11.52
Age, Customized [units: Participants]
>=18 - <50	68	64	132
>=50 - <65	115	128	243
>=65	80	70	150
ATM Status [units: Participants]
Negative	48	46	94
Positive	200	196	396
Unknown	15	20	35
Gastrectomy Status [units: Participants]
Full	50	68	118
None	136	122	258
Partial	77	72	149
Ethnicity, Customized [units: Participants] Not Hispanic Or Latino	263	262	525
Gender, Male/Female [units: ]
Female	89	77	166
Male	174	185	359
Race, Customized [units: Participants] Asian	263	262	525
Age Continuous ^[1] [units: Years] Mean ± Standard Deviation	57.0 ± 12.08	60.9 ± 9.90	58.9 ± 11.18
Age, Customized ^[2] [units: Participants]
>=18 - <50	12	7	19
>=50 - <65	22	24	46
>=65	14	15	29
Gastrectomy Status ^[3] [units: Participants]
Full	13	13	26
Partial	19	12	31
None	16	21	37
Race/Ethnicity, Customized ^[4] [units: Participants] Not Hispanic or Latino	48	46	94
Race/Ethnicity, Customized ^[5] [units: Participants] Asian	48	46	94

Outcome Measures

1. Primary Outcome Measure: Overall survival [ Time Frame: Survival contact from the date of randomization and then every 8 weeks following objective disease progression and in the 7 days following OS Data Cut off (DCO); Time point(s) at which outcome measure is assessed up to 4 years ]

Measure Type	Primary
Measure Name	Overall survival
Measure Description	Time from the date of randomization until death due to any cause
Time Frame	Survival contact from the date of randomization and then every 8 weeks following objective disease progression and in the 7 days following OS Data Cut off (DCO); Time point(s) at which outcome measure is assessed up to 4 years
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis set population

Reporting Groups

	Description
Olaparib 100 mg tablets bd + Paclitaxel 80 mg/m^2	Olaparib 100 mg tablets bd + Paclitaxel 80 mg/m^2
Placebo tablets bd + Paclitaxel 80 mg/m^2	Placebo tablets bd + Paclitaxel 80 mg/m^2

Measured Values

	Olaparib 100 mg tablets bd + Paclitaxel 80 mg/m^2	Placebo tablets bd + Paclitaxel 80 mg/m^2
Number of Participants Analyzed [units:participants]	263	262
Overall survival [units: participants]	82	62

Statistical Analysis 1 for Overall survival

Groups^[1]	All groups
Method^[3]	Other [Cox proportional hazards model]
P-Value^[4]	0.0262
Hazard Ratio (HR)^[5]	0.79
97.5% Confidence Interval	( 0.63 to 1.00 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

2. Primary Outcome Measure: Overall survival [ Time Frame: Survival contact from the date of randomization and then every 8 weeks following objective disease progression and in the 7 days following OS Data Cut off (DCO); Time point(s) at which outcome measure is assessed up to 4 years ]

Measure Type	Primary
Measure Name	Overall survival
Measure Description	Time from the date of randomization until death due to any cause
Time Frame	Survival contact from the date of randomization and then every 8 weeks following objective disease progression and in the 7 days following OS Data Cut off (DCO); Time point(s) at which outcome measure is assessed up to 4 years
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis set - ATM negative population

Reporting Groups

	Description
Olaparib 100 mg tablets bd + Paclitaxel 80 mg/m^2	Olaparib 100 mg tablets bd + Paclitaxel 80 mg/m^2
Placebo tablets bd + Paclitaxel 80 mg/m^2	Placebo tablets bd + Paclitaxel 80 mg/m^2

Measured Values

	Olaparib 100 mg tablets bd + Paclitaxel 80 mg/m^2	Placebo tablets bd + Paclitaxel 80 mg/m^2
Number of Participants Analyzed [units:participants]	48	46
Overall survival [units: participants]	19	11

Statistical Analysis 1 for Overall survival

Groups^[1]	All groups
Method^[3]	Other [Cox proportional hazards model]
P-Value^[4]	0.2458
Hazard Ratio (HR)^[5]	0.73
97.5% Confidence Interval	( 0.40 to 1.34 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

3. Secondary Outcome Measure: Progression-Free Survival (PFS) [ Time Frame: Scans taken at baseline and then follow up assessments taken every 8 weeks up to Week 40 and then every 16 weeks until objective disease progression as defined by RECIST 1.1, assessed up to 3 years ]

Measure Type	Secondary
Measure Name	Progression-Free Survival (PFS)
Measure Description	Time from randomization until the date of objective radiological disease progression according to RECIST (v1.1) or death by any cause in the absence of progression. Objective progression is defined as at least a 20% increase in the sum of the diameters of the target lesions (compared to previous minimum sum) or an overall non-target lesion assessment of progression or a new lesion.
Time Frame	Scans taken at baseline and then follow up assessments taken every 8 weeks up to Week 40 and then every 16 weeks until objective disease progression as defined by RECIST 1.1, assessed up to 3 years
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
FAS analysis set population

Reporting Groups

	Description
Olaparib 100 mg tablets bd + Paclitaxel 80 mg/m^2	Olaparib 100 mg tablets bd + Paclitaxel 80 mg/m^2
Placebo tablets bd + Paclitaxel 80 mg/m^2	Placebo tablets bd + Paclitaxel 80 mg/m^2

Measured Values

	Olaparib 100 mg tablets bd + Paclitaxel 80 mg/m^2	Placebo tablets bd + Paclitaxel 80 mg/m^2
Number of Participants Analyzed [units:participants]	263	262
Progression-Free Survival (PFS) [units: participants]	47	29

Statistical Analysis 1 for Progression-Free Survival (PFS)

Groups^[1]	All groups
Method^[3]	Other [Cox proportional hazards model]
P-Value^[4]	0.0645
Hazard Ratio (HR)^[5]	0.84
97.5% Confidence Interval	( 0.67 to 1.04 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

4. Secondary Outcome Measure: Progression-Free Survival (PFS) [ Time Frame: Scans taken at baseline and then follow up assessments taken every 8 weeks up to Week 40 and then every 16 weeks until objective disease progression as defined by RECIST 1.1, assessed up to 3 years ]

Measure Type	Secondary
Measure Name	Progression-Free Survival (PFS)
Measure Description	Time from randomization until the date of objective radiological disease progression according to RECIST (v1.1) or death by any cause in the absence of progression. Objective progression is defined as at least a 20% increase in the sum of the diameters of the target lesions (compared to previous minimum sum) or an overall non-target lesion assessment of progression or a new lesion.
Time Frame	Scans taken at baseline and then follow up assessments taken every 8 weeks up to Week 40 and then every 16 weeks until objective disease progression as defined by RECIST 1.1, assessed up to 3 years
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
FAS analysis set - ATM negative population

Reporting Groups

	Description
Olaparib 100 mg tablets bd + Paclitaxel 80 mg/m^2	Olaparib 100 mg tablets bd + Paclitaxel 80 mg/m^2
Placebo tablets bd + Paclitaxel 80 mg/m^2	Placebo tablets bd + Paclitaxel 80 mg/m^2

Measured Values

	Olaparib 100 mg tablets bd + Paclitaxel 80 mg/m^2	Placebo tablets bd + Paclitaxel 80 mg/m^2
Number of Participants Analyzed [units:participants]	48	46
Progression-Free Survival (PFS) [units: participants]	11	7

Statistical Analysis 1 for Progression-Free Survival (PFS)

Groups^[1]	All groups
Method^[3]	Other [Cox proportional hazards model]
P-Value^[4]	0.2199
Hazard Ratio (HR)^[5]	0.74
97.5% Confidence Interval	( 0.42 to 1.29 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

5. Secondary Outcome Measure: Number of Patients with Objective Response. [ Time Frame: Scans taken at baseline and then follow up assessments taken every 8 weeks up to Week 40 and then every 16 weeks until objective disease progression as defined by RECIST 1.1, assessed up to 3 years ]

Measure Type	Secondary
Measure Name	Number of Patients with Objective Response.
Measure Description	Number of patients with objective response. Per RECIST 1.1, complete response (CR) is disappearance of all target lesions since baseline; partial response (PR) is at least a 30% decrease in the sum of the diameters of target lesions. Overall Response = CR + PR.
Time Frame	Scans taken at baseline and then follow up assessments taken every 8 weeks up to Week 40 and then every 16 weeks until objective disease progression as defined by RECIST 1.1, assessed up to 3 years
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis set population

Reporting Groups

	Description
Olaparib 100 mg tablets bd + Paclitaxel 80 mg/m^2	Olaparib 100 mg tablets bd + Paclitaxel 80 mg/m^2
Placebo tablets bd + Paclitaxel 80 mg/m^2	Placebo tablets bd + Paclitaxel 80 mg/m^2

Measured Values

	Olaparib 100 mg tablets bd + Paclitaxel 80 mg/m^2	Placebo tablets bd + Paclitaxel 80 mg/m^2
Number of Participants Analyzed [units:participants]	263	262
Number of Patients with Objective Response. [units: participants]	44	28

Statistical Analysis 1 for Number of Patients with Objective Response.

Groups^[1]	All groups
Method^[3]	Regression, Logistic
P-Value^[4]	0.0548
Odds Ratio (OR)^[5]	1.69
97.5% Confidence Interval	( 0.92 to 3.17 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

6. Secondary Outcome Measure: Number of Patients Objective Response [ Time Frame: Scans taken at baseline and then follow up assessments taken every 8 weeks up to Week 40 and then every 16 weeks until objective disease progression as defined by RECIST 1.1, assessed up to 3 years ]

Measure Type	Secondary
Measure Name	Number of Patients Objective Response
Measure Description	Number of patients with objective response. Per RECIST 1.1, complete response (CR) is disappearance of all target lesions since baseline; partial response (PR) is at least a 30% decrease in the sum of the diameters of target lesions. Overall Response = CR + PR.
Time Frame	Scans taken at baseline and then follow up assessments taken every 8 weeks up to Week 40 and then every 16 weeks until objective disease progression as defined by RECIST 1.1, assessed up to 3 years
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Full analysis set - ATM negative population

Reporting Groups

	Description
Olaparib 100 mg tablets bd + Paclitaxel 80 mg/m^2	Olaparib 100 mg tablets bd + Paclitaxel 80 mg/m^2
Placebo tablets bd + Paclitaxel 80 mg/m^2	Placebo tablets bd + Paclitaxel 80 mg/m^2

Measured Values

	Olaparib 100 mg tablets bd + Paclitaxel 80 mg/m^2	Placebo tablets bd + Paclitaxel 80 mg/m^2
Number of Participants Analyzed [units:participants]	48	46
Number of Patients Objective Response [units: participants]	12	5

Statistical Analysis 1 for Number of Patients Objective Response

Groups^[1]	All groups
Method^[3]	Regression, Logistic
P-Value^[4]	0.0309
Odds Ratio (OR)^[5]	4.24
97.5% Confidence Interval	( 0.95 to 23.23 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

7. Secondary Outcome Measure: Number of Patients with deterioration of Health Related Quality of Life (HRQoL) as assessed by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Questionnaire Core 30 item module (QLQ-C30) global HRQoL scale [ Time Frame: Pre-treatment , Day 29 and then every 4 weeks until discontinuation, assessed up to 3 years ]

Measure Type	Secondary
Measure Name	Number of Patients with deterioration of Health Related Quality of Life (HRQoL) as assessed by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Questionnaire Core 30 item module (QLQ-C30) global HRQoL scale
Measure Description	Number of patients with a clinically important deterioration in the global HRQoL score or death by any cause in the absence of a clincially meaningful symptom deterioration
Time Frame	Pre-treatment , Day 29 and then every 4 weeks until discontinuation, assessed up to 3 years
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Patients whose baseline HRQoL score >=10 in full analysis set population

Reporting Groups

	Description
Olaparib 100 mg tablets bd + Paclitaxel 80 mg/m^2	Olaparib 100 mg tablets bd + Paclitaxel 80 mg/m^2
Placebo tablets bd + Paclitaxel 80 mg/m^2	Placebo tablets bd + Paclitaxel 80 mg/m^2

Measured Values

	Olaparib 100 mg tablets bd + Paclitaxel 80 mg/m^2	Placebo tablets bd + Paclitaxel 80 mg/m^2
Number of Participants Analyzed [units:participants]	240	249
Number of Patients with deterioration of Health Related Quality of Life (HRQoL) as assessed by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Questionnaire Core 30 item module (QLQ-C30) global HRQoL scale [units: participants]	160	177

Statistical Analysis 1 for Number of Patients with deterioration of Health Related Quality of Life (HRQoL) as assessed by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Questionnaire Core 30 item module (QLQ-C30) global HRQoL scale

Groups^[1]	All groups
Method^[3]	Other [Cox proportional hazards model]
P-Value^[4]	0.0716
Hazard Ratio (HR)^[5]	0.82
97.5% Confidence Interval	( 0.64 to 1.05 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

8. Secondary Outcome Measure: Number of Patients with deterioration of Health Related Quality of Life (HRQoL) as assessed by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Questionnaire Core 30 item module (QLQ-C30) global HRQoL scale [ Time Frame: Pre-treatment , Day 29 and then every 4 weeks until discontinuation, assessed up to 3 years ]

Measure Type	Secondary
Measure Name	Number of Patients with deterioration of Health Related Quality of Life (HRQoL) as assessed by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Questionnaire Core 30 item module (QLQ-C30) global HRQoL scale
Measure Description	Number of patients with a clinically important deterioration in the global HRQoL score or death by any cause in the absence of a clincially meaningful symptom deterioration
Time Frame	Pre-treatment , Day 29 and then every 4 weeks until discontinuation, assessed up to 3 years
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Patients whose baseline HRQoL score >=10 in full analysis set ATM negative population

Reporting Groups

	Description
Olaparib 100 mg tablets bd + Paclitaxel 80 mg/m^2	Olaparib 100 mg tablets bd + Paclitaxel 80 mg/m^2
Placebo tablets bd + Paclitaxel 80 mg/m^2	Placebo tablets bd + Paclitaxel 80 mg/m^2

Measured Values

	Olaparib 100 mg tablets bd + Paclitaxel 80 mg/m^2	Placebo tablets bd + Paclitaxel 80 mg/m^2
Number of Participants Analyzed [units:participants]	41	43
Number of Patients with deterioration of Health Related Quality of Life (HRQoL) as assessed by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Questionnaire Core 30 item module (QLQ-C30) global HRQoL scale [units: participants]	29	33

Statistical Analysis 1 for Number of Patients with deterioration of Health Related Quality of Life (HRQoL) as assessed by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Questionnaire Core 30 item module (QLQ-C30) global HRQoL scale

Groups^[1]	All groups
Method^[3]	Other [Cox proportional hazards model]
P-Value^[4]	0.0927
Hazard Ratio (HR)^[5]	0.63
97.5% Confidence Interval	( 0.34 to 1.16 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[4]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[5]	Other relevant estimation information:
	No text entered.

9. Secondary Outcome Measure: Time to response [ Time Frame: Scans taken at baseline and then follow up assessments taken every 8 weeks up to Week 40 and then every 16 weeks until objective disease progression as defined by RECIST 1.1, assessed up to 3 years ]

Measure Type	Secondary
Measure Name	Time to response
Measure Description	Time from randomization to the first onset of a confirmed objective tumour response
Time Frame	Scans taken at baseline and then follow up assessments taken every 8 weeks up to Week 40 and then every 16 weeks until objective disease progression as defined by RECIST 1.1, assessed up to 3 years
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Patients with objective response in full analysis set population

Reporting Groups

	Description
Olaparib 100 mg tablets bd + Paclitaxel 80 mg/m^2	Olaparib 100 mg tablets bd + Paclitaxel 80 mg/m^2
Placebo tablets bd + Paclitaxel 80 mg/m^2	Placebo tablets bd + Paclitaxel 80 mg/m^2

Measured Values

	Olaparib 100 mg tablets bd + Paclitaxel 80 mg/m^2	Placebo tablets bd + Paclitaxel 80 mg/m^2
Number of Participants Analyzed [units:participants]	44	28
Time to response [units: days] Median (Inter-Quartile Range)	57.0 (54.5 to 64.0)	57.0 (56.0 to 111.5)

No statistical analysis provided for Time to response

10. Secondary Outcome Measure: Time to response [ Time Frame: Scans taken at baseline and then follow up assessments taken every 8 weeks up to Week 40 and then every 16 weeks until objective disease progression as defined by RECIST 1.1, assessed up to 3 years ]

Measure Type	Secondary
Measure Name	Time to response
Measure Description	Time from randomization to the first onset of a confirmed objective tumour response
Time Frame	Scans taken at baseline and then follow up assessments taken every 8 weeks up to Week 40 and then every 16 weeks until objective disease progression as defined by RECIST 1.1, assessed up to 3 years
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Patients with objective response in full analysis set ATM negative population

Reporting Groups

	Description
Olaparib 100 mg tablets bd + Paclitaxel 80 mg/m^2	Olaparib 100 mg tablets bd + Paclitaxel 80 mg/m^2
Placebo tablets bd + Paclitaxel 80 mg/m^2	Placebo tablets bd + Paclitaxel 80 mg/m^2

Measured Values

	Olaparib 100 mg tablets bd + Paclitaxel 80 mg/m^2	Placebo tablets bd + Paclitaxel 80 mg/m^2
Number of Participants Analyzed [units:participants]	12	5
Time to response [units: days] Median (Inter-Quartile Range)	57.5 (57.0 to 113.0)	57.0 (55.0 to 58.0)

No statistical analysis provided for Time to response

11. Secondary Outcome Measure: Duration of response [ Time Frame: Scans taken at baseline and then follow up assessments taken every 8 weeks up to Week 40 and then every 16 weeks until objective disease progression as defined by RECIST 1.1, assessed up to 3 years ]

Measure Type	Secondary
Measure Name	Duration of response
Measure Description	Time from the first documentation of CR/PR until the date of progression, or the last evaluable RECIST assessment for patients taht do not progress or progress after two or more missed visits
Time Frame	Scans taken at baseline and then follow up assessments taken every 8 weeks up to Week 40 and then every 16 weeks until objective disease progression as defined by RECIST 1.1, assessed up to 3 years
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Patients with objective response in full analysis set population

Reporting Groups

	Description
Olaparib 100 mg tablets bd + Paclitaxel 80 mg/m^2	Olaparib 100 mg tablets bd + Paclitaxel 80 mg/m^2
Placebo tablets bd + Paclitaxel 80 mg/m^2	Placebo tablets bd + Paclitaxel 80 mg/m^2

Measured Values

	Olaparib 100 mg tablets bd + Paclitaxel 80 mg/m^2	Placebo tablets bd + Paclitaxel 80 mg/m^2
Number of Participants Analyzed [units:participants]	44	28
Duration of response [units: days] Median (Inter-Quartile Range)	166.0 (89.0 to 218.0)	64.0 (54.0 to 186.0)

No statistical analysis provided for Duration of response

12. Secondary Outcome Measure: Duration of response [ Time Frame: Scans taken at baseline and then follow up assessments taken every 8 weeks up to Week 40 and then every 16 weeks until objective disease progression as defined by RECIST 1.1, assessed up to 3 years ]

Measure Type	Secondary
Measure Name	Duration of response
Measure Description	Time from the first documentation of CR/PR until the date of progression, or the last evaluable RECIST assessment for patients taht do not progress or progress after two or more missed visits
Time Frame	Scans taken at baseline and then follow up assessments taken every 8 weeks up to Week 40 and then every 16 weeks until objective disease progression as defined by RECIST 1.1, assessed up to 3 years
Safety Issue?

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Patients with objective response in full analysis set ATM negative population

Reporting Groups

	Description
Olaparib 100 mg tablets bd + Paclitaxel 80 mg/m^2	Olaparib 100 mg tablets bd + Paclitaxel 80 mg/m^2
Placebo tablets bd + Paclitaxel 80 mg/m^2	Placebo tablets bd + Paclitaxel 80 mg/m^2

Measured Values

	Olaparib 100 mg tablets bd + Paclitaxel 80 mg/m^2	Placebo tablets bd + Paclitaxel 80 mg/m^2
Number of Participants Analyzed [units:participants]	12	5
Duration of response [units: days] Median (Inter-Quartile Range)	171.0 (124.0 to 350.0)	108.0 (57.0 to 113.0)

No statistical analysis provided for Duration of response

Serious Adverse Events

Time Frame	No text entered.
Additional Description	Participants in the Full Analysis Set (i.e., 263 and 262) were monitored/assessed for All-Cause Mortality/Overall Survival and participants in the Safety Set (i.e., 262 and 259) were monitored/assessed for Serious and Other (Not Including Serious) Adverse Events.

Reporting Groups

	Description
Olaparib 100 mg tablets bd + Paclitaxel 80 mg/m^2	Olaparib 100 mg tablets bd + Paclitaxel 80 mg/m^2
Placebo tablets bd + Paclitaxel 80 mg/m^2	Placebo tablets bd + Paclitaxel 80 mg/m^2

Serious Adverse Events

Olaparib 100 mg tablets bd + Paclitaxel 80 mg/m^2

Placebo tablets bd + Paclitaxel 80 mg/m^2

Total, serious adverse events

# participants affected / at risk

92/262 (35.11%)

65/259 (25.10%)

Metabolism and nutrition disorders

Dehydration¹,^†

# participants affected / at risk

1/262 (0.38%)

0/259 (0.00%)

# events

Blood and lymphatic system disorders

Anaemia¹,^†

# participants affected / at risk

2/262 (0.76%)

0/259 (0.00%)

# events

Blood and lymphatic system disorders

Bone marrow disorder¹,^†

# participants affected / at risk

6/262 (2.29%)

3/259 (1.16%)

# events

Blood and lymphatic system disorders

Disseminated intravascular coagulation¹,^†

# participants affected / at risk

0/262 (0.00%)

1/259 (0.39%)

# events

Blood and lymphatic system disorders

Febrile neutropenia¹,^†

# participants affected / at risk

5/262 (1.91%)

2/259 (0.77%)

# events

Blood and lymphatic system disorders

Granulocytopenia¹,^†

# participants affected / at risk

5/262 (1.91%)

2/259 (0.77%)

# events

Blood and lymphatic system disorders

Leukopenia¹,^†

# participants affected / at risk

5/262 (1.91%)

0/259 (0.00%)

# events

Blood and lymphatic system disorders

Neutropenia¹,^†

# participants affected / at risk

1/262 (0.38%)

2/259 (0.77%)

# events

Cardiac disorders

Cardiac arrest¹,^†

# participants affected / at risk

1/262 (0.38%)

0/259 (0.00%)

# events

Cardiac disorders

Cardiac failure¹,^†

# participants affected / at risk

0/262 (0.00%)

1/259 (0.39%)

# events

Ear and labyrinth disorders

Hypoacusis¹,^†

# participants affected / at risk

0/262 (0.00%)

1/259 (0.39%)

# events

Gastrointestinal disorders

Abdominal pain¹,^†

# participants affected / at risk

4/262 (1.53%)

3/259 (1.16%)

# events

Gastrointestinal disorders

Ascites¹,^†

# participants affected / at risk

0/262 (0.00%)

1/259 (0.39%)

# events

Gastrointestinal disorders

Diarrhoea¹,^†

# participants affected / at risk

2/262 (0.76%)

1/259 (0.39%)

# events

Gastrointestinal disorders

Dyspepsia¹,^†

# participants affected / at risk

1/262 (0.38%)

0/259 (0.00%)

# events

Gastrointestinal disorders

Dysphagia¹,^†

# participants affected / at risk

1/262 (0.38%)

1/259 (0.39%)

# events

Gastrointestinal disorders

Gastric haemorrhage¹,^†

# participants affected / at risk

1/262 (0.38%)

1/259 (0.39%)

# events

Gastrointestinal disorders

Gastrointestinal haemorrhage¹,^†

# participants affected / at risk

1/262 (0.38%)

2/259 (0.77%)

# events

Gastrointestinal disorders

Gastrooesophageal reflux disease¹,^†

# participants affected / at risk

1/262 (0.38%)

0/259 (0.00%)

# events

Gastrointestinal disorders

Haematemesis¹,^†

# participants affected / at risk

1/262 (0.38%)

1/259 (0.39%)

# events

Gastrointestinal disorders

Haematochezia¹,^†

# participants affected / at risk

0/262 (0.00%)

1/259 (0.39%)

# events

Gastrointestinal disorders

Ileus¹,^†

# participants affected / at risk

4/262 (1.53%)

4/259 (1.54%)

# events

Gastrointestinal disorders

Intestinal dilatation¹,^†

# participants affected / at risk

1/262 (0.38%)

0/259 (0.00%)

# events

Gastrointestinal disorders

Intestinal obstruction¹,^†

# participants affected / at risk

3/262 (1.15%)

1/259 (0.39%)

# events

Gastrointestinal disorders

Melaena¹,^†

# participants affected / at risk

0/262 (0.00%)

1/259 (0.39%)

# events

Gastrointestinal disorders

Nausea¹,^†

# participants affected / at risk

3/262 (1.15%)

1/259 (0.39%)

# events

Gastrointestinal disorders

Obstruction gastric¹,^†

# participants affected / at risk

1/262 (0.38%)

1/259 (0.39%)

# events

Gastrointestinal disorders

Oesophageal obstruction¹,^†

# participants affected / at risk

1/262 (0.38%)

0/259 (0.00%)

# events

Gastrointestinal disorders

Upper gastrointestinal haemorrhage¹,^†

# participants affected / at risk

0/262 (0.00%)

1/259 (0.39%)

# events

Gastrointestinal disorders

Vomiting¹,^†

# participants affected / at risk

4/262 (1.53%)

4/259 (1.54%)

# events

General disorders and administration site conditions

Asthenia¹,^†

# participants affected / at risk

2/262 (0.76%)

2/259 (0.77%)

# events

General disorders and administration site conditions

Chest pain¹,^†

# participants affected / at risk

0/262 (0.00%)

1/259 (0.39%)

# events

General disorders and administration site conditions

Death¹,^†

# participants affected / at risk

1/262 (0.38%)

0/259 (0.00%)

# events

General disorders and administration site conditions

Fatigue¹,^†

# participants affected / at risk

2/262 (0.76%)

1/259 (0.39%)

# events

General disorders and administration site conditions

Multiple organ dysfunction syndrome¹,^†

# participants affected / at risk

0/262 (0.00%)

2/259 (0.77%)

# events

General disorders and administration site conditions

Pyrexia¹,^†

# participants affected / at risk

4/262 (1.53%)

4/259 (1.54%)

# events

Hepatobiliary disorders

Bile duct stenosis¹,^†

# participants affected / at risk

1/262 (0.38%)

0/259 (0.00%)

# events

Hepatobiliary disorders

Bile duct stone¹,^†

# participants affected / at risk

0/262 (0.00%)

1/259 (0.39%)

# events

Hepatobiliary disorders

Cholangitis¹,^†

# participants affected / at risk

2/262 (0.76%)

0/259 (0.00%)

# events

Hepatobiliary disorders

Cholangitis acute¹,^†

# participants affected / at risk

1/262 (0.38%)

0/259 (0.00%)

# events

Hepatobiliary disorders

Cholecystitis¹,^†

# participants affected / at risk

1/262 (0.38%)

1/259 (0.39%)

# events

Hepatobiliary disorders

Dilatation intrahepatic duct acquired¹,^†

# participants affected / at risk

1/262 (0.38%)

0/259 (0.00%)

# events

Hepatobiliary disorders

Hepatic function abnormal¹,^†

# participants affected / at risk

2/262 (0.76%)

0/259 (0.00%)

# events

Hepatobiliary disorders

Jaundice cholestatic¹,^†

# participants affected / at risk

3/262 (1.15%)

0/259 (0.00%)

# events

Hepatobiliary disorders

Liver injury¹,^†

# participants affected / at risk

1/262 (0.38%)

0/259 (0.00%)

# events

Infections and infestations

Abdominal infection¹,^†

# participants affected / at risk

1/262 (0.38%)

0/259 (0.00%)

# events

Infections and infestations

Atypical mycobacterial infection¹,^†

# participants affected / at risk

0/262 (0.00%)

1/259 (0.39%)

# events

Infections and infestations

Biliary tract infection¹,^†

# participants affected / at risk

1/262 (0.38%)

0/259 (0.00%)

# events

Infections and infestations

Bronchiolitis¹,^†

# participants affected / at risk

1/262 (0.38%)

0/259 (0.00%)

# events

Infections and infestations

Bronchitis¹,^†

# participants affected / at risk

1/262 (0.38%)

0/259 (0.00%)

# events

Infections and infestations

Device related infection¹,^†

# participants affected / at risk

2/262 (0.76%)

0/259 (0.00%)

# events

Infections and infestations

Enterocolitis infectious¹,^†

# participants affected / at risk

1/262 (0.38%)

1/259 (0.39%)

# events

Infections and infestations

Gastroenteritis¹,^†

# participants affected / at risk

0/262 (0.00%)

1/259 (0.39%)

# events

Infections and infestations

Lung infection¹,^†

# participants affected / at risk

2/262 (0.76%)

0/259 (0.00%)

# events

Infections and infestations

Pneumonia¹,^†

# participants affected / at risk

6/262 (2.29%)

4/259 (1.54%)

# events

Infections and infestations

Scrub typhus¹,^†

# participants affected / at risk

1/262 (0.38%)

0/259 (0.00%)

# events

Infections and infestations

Sepsis¹,^†

# participants affected / at risk

1/262 (0.38%)

1/259 (0.39%)

# events

Infections and infestations

Upper respiratory tract infection¹,^†

# participants affected / at risk

2/262 (0.76%)

0/259 (0.00%)

# events

Infections and infestations

Urinary tract infection¹,^†

# participants affected / at risk

2/262 (0.76%)

1/259 (0.39%)

# events

Injury, poisoning and procedural complications

Craniocerebral injury¹,^†

# participants affected / at risk

0/262 (0.00%)

1/259 (0.39%)

# events

Injury, poisoning and procedural complications

Gastrointestinal anastomotic leak¹,^†

# participants affected / at risk

1/262 (0.38%)

0/259 (0.00%)

# events

Injury, poisoning and procedural complications

Humerus fracture¹,^†

# participants affected / at risk

0/262 (0.00%)

1/259 (0.39%)

# events

Injury, poisoning and procedural complications

Splenic rupture¹,^†

# participants affected / at risk

1/262 (0.38%)

0/259 (0.00%)

# events

Injury, poisoning and procedural complications

Subdural haematoma¹,^†

# participants affected / at risk

0/262 (0.00%)

1/259 (0.39%)

# events

Investigations

Alanine aminotransferase increased¹,^†

# participants affected / at risk

1/262 (0.38%)

1/259 (0.39%)

# events

Investigations

Aspartate aminotransferase increased¹,^†

# participants affected / at risk

0/262 (0.00%)

1/259 (0.39%)

# events

Investigations

Blood bilirubin increased¹,^†

# participants affected / at risk

1/262 (0.38%)

0/259 (0.00%)

# events

Investigations

Coagulation test abnormal¹,^†

# participants affected / at risk

1/262 (0.38%)

0/259 (0.00%)

# events

Investigations

Granulocyte count decreased¹,^†

# participants affected / at risk

1/262 (0.38%)

0/259 (0.00%)

# events

Investigations

Neutrophil count decreased¹,^†

# participants affected / at risk

1/262 (0.38%)

0/259 (0.00%)

# events

Investigations

Weight decreased¹,^†

# participants affected / at risk

0/262 (0.00%)

1/259 (0.39%)

# events

Investigations

White blood cell count decreased¹,^†

# participants affected / at risk

1/262 (0.38%)

0/259 (0.00%)

# events

Metabolism and nutrition disorders

Decreased appetite¹,^†

# participants affected / at risk

2/262 (0.76%)

0/259 (0.00%)

# events

Metabolism and nutrition disorders

Hypoproteinaemia¹,^†

# participants affected / at risk

1/262 (0.38%)

0/259 (0.00%)

# events

Musculoskeletal and connective tissue disorders

Back pain¹,^†

# participants affected / at risk

0/262 (0.00%)

1/259 (0.39%)

# events

Musculoskeletal and connective tissue disorders

Muscular weakness¹,^†

# participants affected / at risk

1/262 (0.38%)

0/259 (0.00%)

# events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Rectal cancer¹,^†

# participants affected / at risk

0/262 (0.00%)

1/259 (0.39%)

# events

Nervous system disorders

Cerebral haemorrhage¹,^†

# participants affected / at risk

1/262 (0.38%)

0/259 (0.00%)

# events

Nervous system disorders

Dizziness¹,^†

# participants affected / at risk

0/262 (0.00%)

1/259 (0.39%)

# events

Nervous system disorders

Epilepsy¹,^†

# participants affected / at risk

0/262 (0.00%)

1/259 (0.39%)

# events

Nervous system disorders

Headache¹,^†

# participants affected / at risk

0/262 (0.00%)

1/259 (0.39%)

# events

Nervous system disorders

Loss of consciousness¹,^†

# participants affected / at risk

1/262 (0.38%)

0/259 (0.00%)

# events

Nervous system disorders

Optic neuritis¹,^†

# participants affected / at risk

0/262 (0.00%)

1/259 (0.39%)

# events

Nervous system disorders

Syncope¹,^†

# participants affected / at risk

0/262 (0.00%)

1/259 (0.39%)

# events

Product issues

Device malfunction¹,^†

# participants affected / at risk

1/262 (0.38%)

0/259 (0.00%)

# events

Product issues

Stent malfunction¹,^†

# participants affected / at risk

1/262 (0.38%)

0/259 (0.00%)

# events

Psychiatric disorders

Delirium¹,^†

# participants affected / at risk

1/262 (0.38%)

0/259 (0.00%)

# events

Psychiatric disorders

Suicide attempt¹,^†

# participants affected / at risk

1/262 (0.38%)

0/259 (0.00%)

# events

Renal and urinary disorders

Acute kidney injury¹,^†

# participants affected / at risk

1/262 (0.38%)

1/259 (0.39%)

# events

Renal and urinary disorders

Calculus bladder¹,^†

# participants affected / at risk

0/262 (0.00%)

1/259 (0.39%)

# events

Renal and urinary disorders

Haematuria¹,^†

# participants affected / at risk

0/262 (0.00%)

1/259 (0.39%)

# events

Renal and urinary disorders

Hydronephrosis¹,^†

# participants affected / at risk

1/262 (0.38%)

0/259 (0.00%)

# events

Renal and urinary disorders

Urinary tract obstruction¹,^†

# participants affected / at risk

0/262 (0.00%)

1/259 (0.39%)

# events

Reproductive system and breast disorders

Benign prostatic hyperplasia¹,^†

# participants affected / at risk

0/262 (0.00%)

1/259 (0.39%)

# events

Respiratory, thoracic and mediastinal disorders

Chylothorax¹,^†

# participants affected / at risk

0/262 (0.00%)

1/259 (0.39%)

# events

Respiratory, thoracic and mediastinal disorders

Cough¹,^†

# participants affected / at risk

0/262 (0.00%)

1/259 (0.39%)

# events

Respiratory, thoracic and mediastinal disorders

Dyspnoea¹,^†

# participants affected / at risk

0/262 (0.00%)

1/259 (0.39%)

# events

Respiratory, thoracic and mediastinal disorders

Interstitial lung disease¹,^†

# participants affected / at risk

1/262 (0.38%)

0/259 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Pleural effusion¹,^†

# participants affected / at risk

0/262 (0.00%)

1/259 (0.39%)

# events

Respiratory, thoracic and mediastinal disorders

Pneumonia aspiration¹,^†

# participants affected / at risk

0/262 (0.00%)

2/259 (0.77%)

# events

Respiratory, thoracic and mediastinal disorders

Pneumonitis¹,^†

# participants affected / at risk

0/262 (0.00%)

1/259 (0.39%)

# events

Respiratory, thoracic and mediastinal disorders

Pneumothorax¹,^†

# participants affected / at risk

1/262 (0.38%)

0/259 (0.00%)

# events

Respiratory, thoracic and mediastinal disorders

Respiratory failure¹,^†

# participants affected / at risk

1/262 (0.38%)

0/259 (0.00%)

# events

Skin and subcutaneous tissue disorders

Dermal cyst¹,^†

# participants affected / at risk

0/262 (0.00%)

1/259 (0.39%)

# events

Vascular disorders

Deep vein thrombosis¹,^†

# participants affected / at risk

2/262 (0.76%)

0/259 (0.00%)

# events

Vascular disorders

Venous thrombosis¹,^†

# participants affected / at risk

2/262 (0.76%)

0/259 (0.00%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 19.0

Other Adverse Events

Time Frame	No text entered.
Additional Description	Participants in the Full Analysis Set (i.e., 263 and 262) were monitored/assessed for All-Cause Mortality/Overall Survival and participants in the Safety Set (i.e., 262 and 259) were monitored/assessed for Serious and Other (Not Including Serious) Adverse Events.

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

	Description
Olaparib 100 mg tablets bd + Paclitaxel 80 mg/m^2	Olaparib 100 mg tablets bd + Paclitaxel 80 mg/m^2
Placebo tablets bd + Paclitaxel 80 mg/m^2	Placebo tablets bd + Paclitaxel 80 mg/m^2

Other Adverse Events

Olaparib 100 mg tablets bd + Paclitaxel 80 mg/m^2

Placebo tablets bd + Paclitaxel 80 mg/m^2

Total, other (not including serious) adverse events

# participants affected / at risk

257/262 (98.09%)

253/259 (97.68%)

Musculoskeletal and connective tissue disorders

Arthralgia¹,^†

# participants affected / at risk

17/262 (6.49%)

15/259 (5.79%)

# events

Blood and lymphatic system disorders

Anaemia¹,^†

# participants affected / at risk

99/262 (37.79%)

62/259 (23.94%)

# events

156

101

Blood and lymphatic system disorders

Leukopenia¹,^†

# participants affected / at risk

71/262 (27.10%)

57/259 (22.01%)

# events

232

177

Blood and lymphatic system disorders

Neutropenia¹,^†

# participants affected / at risk

122/262 (46.56%)

108/259 (41.70%)

# events

373

300

Gastrointestinal disorders

Abdominal distension¹,^†

# participants affected / at risk

19/262 (7.25%)

19/259 (7.34%)

# events

Gastrointestinal disorders

Abdominal pain¹,^†

# participants affected / at risk

23/262 (8.78%)

28/259 (10.81%)

# events

Gastrointestinal disorders

Abdominal pain upper¹,^†

# participants affected / at risk

20/262 (7.63%)

15/259 (5.79%)

# events

Gastrointestinal disorders

Constipation¹,^†

# participants affected / at risk

38/262 (14.50%)

50/259 (19.31%)

# events

Gastrointestinal disorders

Diarrhoea¹,^†

# participants affected / at risk

66/262 (25.19%)

51/259 (19.69%)

# events

102

Gastrointestinal disorders

Dyspepsia¹,^†

# participants affected / at risk

13/262 (4.96%)

13/259 (5.02%)

# events

Gastrointestinal disorders

Nausea¹,^†

# participants affected / at risk

75/262 (28.63%)

63/259 (24.32%)

# events

121

Gastrointestinal disorders

Stomatitis¹,^†

# participants affected / at risk

21/262 (8.02%)

12/259 (4.63%)

# events

Gastrointestinal disorders

Vomiting¹,^†

# participants affected / at risk

45/262 (17.18%)

43/259 (16.60%)

# events

General disorders and administration site conditions

Asthenia¹,^†

# participants affected / at risk

45/262 (17.18%)

35/259 (13.51%)

# events

General disorders and administration site conditions

Fatigue¹,^†

# participants affected / at risk

48/262 (18.32%)

52/259 (20.08%)

# events

General disorders and administration site conditions

Malaise¹,^†

# participants affected / at risk

15/262 (5.73%)

12/259 (4.63%)

# events

General disorders and administration site conditions

Pyrexia¹,^†

# participants affected / at risk

34/262 (12.98%)

36/259 (13.90%)

# events

Infections and infestations

Nasopharyngitis¹,^†

# participants affected / at risk

16/262 (6.11%)

9/259 (3.47%)

# events

Infections and infestations

Upper respiratory tract infection¹,^†

# participants affected / at risk

19/262 (7.25%)

14/259 (5.41%)

# events

Investigations

Alanine aminotransferase increased¹,^†

# participants affected / at risk

31/262 (11.83%)

14/259 (5.41%)

# events

Investigations

Aspartate aminotransferase increased¹,^†

# participants affected / at risk

23/262 (8.78%)

16/259 (6.18%)

# events

Investigations

Blood bilirubin increased¹,^†

# participants affected / at risk

10/262 (3.82%)

14/259 (5.41%)

# events

Investigations

Haemoglobin decreased¹,^†

# participants affected / at risk

18/262 (6.87%)

20/259 (7.72%)

# events

Investigations

Neutrophil count decreased¹,^†

# participants affected / at risk

67/262 (25.57%)

38/259 (14.67%)

# events

188

Investigations

Platelet count decreased¹,^†

# participants affected / at risk

20/262 (7.63%)

12/259 (4.63%)

# events

Investigations

White blood cell count decreased¹,^†

# participants affected / at risk

60/262 (22.90%)

48/259 (18.53%)

# events

165

116

Metabolism and nutrition disorders

Decreased appetite¹,^†

# participants affected / at risk

86/262 (32.82%)

69/259 (26.64%)

# events

127

Metabolism and nutrition disorders

Hypoalbuminaemia¹,^†

# participants affected / at risk

14/262 (5.34%)

13/259 (5.02%)

# events

Metabolism and nutrition disorders

Hypokalaemia¹,^†

# participants affected / at risk

21/262 (8.02%)

16/259 (6.18%)

# events

Musculoskeletal and connective tissue disorders

Back pain¹,^†

# participants affected / at risk

8/262 (3.05%)

13/259 (5.02%)

# events

Musculoskeletal and connective tissue disorders

Myalgia¹,^†

# participants affected / at risk

37/262 (14.12%)

35/259 (13.51%)

# events

Nervous system disorders

Dizziness¹,^†

# participants affected / at risk

11/262 (4.20%)

14/259 (5.41%)

# events

Nervous system disorders

Hypoaesthesia¹,^†

# participants affected / at risk

20/262 (7.63%)

16/259 (6.18%)

# events

Nervous system disorders

Neuropathy peripheral¹,^†

# participants affected / at risk

41/262 (15.65%)

42/259 (16.22%)

# events

Nervous system disorders

Peripheral sensory neuropathy¹,^†

# participants affected / at risk

41/262 (15.65%)

29/259 (11.20%)

# events

Psychiatric disorders

Insomnia¹,^†

# participants affected / at risk

20/262 (7.63%)

19/259 (7.34%)

# events

Respiratory, thoracic and mediastinal disorders

Cough¹,^†

# participants affected / at risk

22/262 (8.40%)

24/259 (9.27%)

# events

Skin and subcutaneous tissue disorders

Alopecia¹,^†

# participants affected / at risk

112/262 (42.75%)

116/259 (44.79%)

# events

112

117

Skin and subcutaneous tissue disorders

Pruritus¹,^†

# participants affected / at risk

10/262 (3.82%)

17/259 (6.56%)

# events

Skin and subcutaneous tissue disorders

Rash¹,^†

# participants affected / at risk

35/262 (13.36%)

24/259 (9.27%)

# events

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 19.0

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days . The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: At least 60 days prior to submission of any material for publication or presentation, Institution and Principal Investigator (PI) shall jointly provide AstraZeneca with such material for review. If requested in writing by AstraZeneca, Institution and PI shall withhold material from submission for publication or presentation for an additional 90 days from the date of AstraZeneca’s request to allow for the filing patent application or preserve its proprietary rights in the information.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact

Name/Title:	Gershon Locker Global Clinical Lead (GCL)
Organization:	AstraZeneca
E-mail:	[email protected]

Documents available

Study protocol-redacted
Download
CSR Synopsis
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Investigators

Principal Investigator

Yung-Jue Bang

Seoul National University, College of Medicine and Cancer Research Institute, Republic of Korea

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Study protocol-redacted

CSR Synopsis

Trial Results Summaries