Trial Outcomes & Findings for A Study of Adavosertib as Treatment for Uterine Serous Carcinoma (NCT NCT04590248)

NCT ID: NCT04590248

Last Updated: 2023-08-14

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 109 participants
• Primary outcome timeframe: up to 75 weeks
• Results posted on: 2023-08-14

Participant Flow

The study was conducted at 28 sites in 5 countries (United States, Canada, France, Italy and Spain) from 30-November-2020 to 07-February-2023.

Participants had been through a screening period of 28 days, followed by assessments as per schedule of activities.

Participant milestones

Measure	Adavosertib Participants received adavosertib 300 mg administered orally, once daily on Days 1 to 5 followed by 2 days off and Days 8 to 12 (21 days treatment cycle).
Overall Study STARTED	109
Overall Study COMPLETED	90
Overall Study NOT COMPLETED	19

Reasons for withdrawal

Measure	Adavosertib Participants received adavosertib 300 mg administered orally, once daily on Days 1 to 5 followed by 2 days off and Days 8 to 12 (21 days treatment cycle).
Overall Study Lost to Follow-up	1
Overall Study Withdrawal by Subject	16
Overall Study Other	2

Baseline Characteristics

A Study of Adavosertib as Treatment for Uterine Serous Carcinoma

Baseline characteristics by cohort

Measure	Adavosertib n=109 Participants Participants received adavosertib 300 mg administered orally, once daily on Days 1 to 5 followed by 2 days off and Days 8 to 12 (21 days treatment cycle).
Age, Continuous	68.8 years STANDARD_DEVIATION 7.05 • n=5 Participants
Sex: Female, Male Female	109 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	98 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	6 Participants n=5 Participants
Race/Ethnicity, Customized Black African or American	9 Participants n=5 Participants
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants
Race/Ethnicity, Customized White	92 Participants n=5 Participants
Race/Ethnicity, Customized Other	3 Participants n=5 Participants
Race/Ethnicity, Customized Missing	4 Participants n=5 Participants

PRIMARY outcome

Timeframe: up to 75 weeks

Population: FAS, which included all participants who received at least one (non-zero) dose of study treatment. Here, overall number of participants analyzed signifies the participant with available data that were analyzed for the outcome measure.

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.

Outcome measures

Measure	Adavosertib n=104 Participants Participants received adavosertib 300 mg administered orally, once daily on Days 1 to 5 followed by 2 days off and Days 8 to 12 (21 days treatment cycle).
Objective Response Rate (ORR)	26 Percentage of participants Interval 17.9 to 35.5

SECONDARY outcome

Timeframe: up to 75 weeks

Population: FAS, which included all participants who received at least one (non-zero) dose of study treatment and had a confirmed response.

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

Outcome measures

Measure	Adavosertib n=27 Participants Participants received adavosertib 300 mg administered orally, once daily on Days 1 to 5 followed by 2 days off and Days 8 to 12 (21 days treatment cycle).
Duration of Response (DoR)	4.7 Months Interval 1.4 to 10.5

SECONDARY outcome

Timeframe: Up to 75 weeks

Population: FAS, which included all participants who received at least one (non-zero) dose of study treatment. Here, overall number of participants analyzed signifies the participant with available data that were analyzed for the outcome measure.

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.

Outcome measures

Measure	Adavosertib n=100 Participants Participants received adavosertib 300 mg administered orally, once daily on Days 1 to 5 followed by 2 days off and Days 8 to 12 (21 days treatment cycle).
Depth of Response	-20.8 Percentage change Standard Deviation 31.60

SECONDARY outcome

Timeframe: Up to 75 weeks

Population: FAS, which included all participants who received at least one (non-zero) dose of study treatment.

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.

Outcome measures

Measure	Adavosertib n=109 Participants Participants received adavosertib 300 mg administered orally, once daily on Days 1 to 5 followed by 2 days off and Days 8 to 12 (21 days treatment cycle).
Progression Free Survival (PFS)	2.8 Months Interval 2.6 to 3.94

SECONDARY outcome

Timeframe: Up to 6 months

Population: FAS, which included all participants who received at least one (non-zero) dose of study treatment.

The progression free survival rate was assessed at 6 months by Kaplan-Meier estimate per RECIST v1.1.

Outcome measures

Measure	Adavosertib n=109 Participants Participants received adavosertib 300 mg administered orally, once daily on Days 1 to 5 followed by 2 days off and Days 8 to 12 (21 days treatment cycle).
Progression Free Survival Rate at 6 Months (PFS6)	18.1 Percentage Interval 10.42 to 27.55

SECONDARY outcome

Timeframe: Up to 75 weeks

Population: FAS, which included all participants who received at least one (non-zero) dose of study treatment.

The time from date of first dose until the date of death due to any cause

Outcome measures

Measure	Adavosertib n=109 Participants Participants received adavosertib 300 mg administered orally, once daily on Days 1 to 5 followed by 2 days off and Days 8 to 12 (21 days treatment cycle).
Overall Survival (OS)	9.6 Months Interval 8.28 to Not calculable due to lack of events near the median.

SECONDARY outcome

Timeframe: Up to 75 weeks

Population: FAS, which included all subjects who received at least one (non-zero) dose of study treatment.

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.

Outcome measures

Measure	Adavosertib n=109 Participants Participants received adavosertib 300 mg administered orally, once daily on Days 1 to 5 followed by 2 days off and Days 8 to 12 (21 days treatment cycle).
Disease Control Rate (DCR)	51.4 Percentage of participants Interval 41.6 to 61.1

SECONDARY outcome

Timeframe: Cycle 1, Day 5 and Cycle 2, Day 5 (pre-dose) (each cycle is 21 days)

Population: The pharmacokinetic analysis set included all dosed participants who had at least one measurable plasma concentration collected post-dose which was obtained without any deviation or event thought to significantly affect the pharmacokinetic analysis. Here, overall number of participants analyzed signifies in each row the participant with available data, that was analyzed for specific time points.

Lowest plasma concentration of adavosertib was evaluated as pharmacokinetic paramerter.

Outcome measures

Measure	Adavosertib n=109 Participants Participants received adavosertib 300 mg administered orally, once daily on Days 1 to 5 followed by 2 days off and Days 8 to 12 (21 days treatment cycle).
Lowest Concentration (Ctrough) of Adavosertib Cycle 1 Day 5	307.2 nanomole (nM) Geometric Coefficient of Variation 105.6
Lowest Concentration (Ctrough) of Adavosertib Cycle 2 Day 5	328.7 nanomole (nM) Geometric Coefficient of Variation 70.3

SECONDARY outcome

Timeframe: Cycle 1, Day 5 and Cycle 2, Day 5 (2 hours post-dose) (each cycle is 21 days)

Population: The pharmacokinetic analysis set included all dosed participants who had at least one measurable plasma concentration collected post-dose which was obtained without any deviation or event thought to significantly affect the pharmacokinetic analysis. Here, overall number of participants analyzed in each row signifies the participant with available data, that was analyzed for specific time points.

Maximum plasma concentration of adavosertib was evaluated as pharmacokinetic parameter.

Outcome measures

Measure	Adavosertib n=109 Participants Participants received adavosertib 300 mg administered orally, once daily on Days 1 to 5 followed by 2 days off and Days 8 to 12 (21 days treatment cycle).
Maximum Concentration (Cmax) of Adavosertib Cycle 1 Day 5	1115.9 nM Geometric Coefficient of Variation 82.1
Maximum Concentration (Cmax) of Adavosertib Cycle 2 Day 5	1356.5 nM Geometric Coefficient of Variation 59.3

SECONDARY outcome

Timeframe: From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks

Population: FAS, which included all participants who received at least one (non-zero) dose of study treatment.

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.

Outcome measures

Measure	Adavosertib n=109 Participants Participants received adavosertib 300 mg administered orally, once daily on Days 1 to 5 followed by 2 days off and Days 8 to 12 (21 days treatment cycle).
Number of Participants With Treatment Emergent Adverse Events (AEs) Any AE	109 Participants
Number of Participants With Treatment Emergent Adverse Events (AEs) Any AE possibly related to treatment	106 Participants
Number of Participants With Treatment Emergent Adverse Events (AEs) Any AE with outcome = death	4 Participants
Number of Participants With Treatment Emergent Adverse Events (AEs) Any AE with outcome = death, possibly related to treatment	1 Participants
Number of Participants With Treatment Emergent Adverse Events (AEs) Any AE of Common Terminology Criteria for Adverse Events (CTCAE) grade 3 or higher	75 Participants
Number of Participants With Treatment Emergent Adverse Events (AEs) Any AE of CTCAE grade 3 or higher, possibly related to treatment	66 Participants
Number of Participants With Treatment Emergent Adverse Events (AEs) Any AE leading to discontinuation of IP	19 Participants
Number of Participants With Treatment Emergent Adverse Events (AEs) Any AE leading to discontinuation of IP, possibly related to treatment	16 Participants
Number of Participants With Treatment Emergent Adverse Events (AEs) Any serious adverse event (SAE) (including events with outcome = death)	50 Participants
Number of Participants With Treatment Emergent Adverse Events (AEs) Any SAE (including events with outcome = death), possibly related to treatment	29 Participants
Number of Participants With Treatment Emergent Adverse Events (AEs) Any SAE leading to discontinuation of investigational product (IP)	10 Participants
Number of Participants With Treatment Emergent Adverse Events (AEs) Any SAE leading to discontinuation of IP, possibly related to treatment	8 Participants
Number of Participants With Treatment Emergent Adverse Events (AEs) Any AE leading to dose modification of IP	79 Participants
Number of Participants With Treatment Emergent Adverse Events (AEs) Any AE leading to dose reduction of IP	62 Participants
Number of Participants With Treatment Emergent Adverse Events (AEs) Any AE leading to dose interruption of IP	72 Participants
Number of Participants With Treatment Emergent Adverse Events (AEs) Any AE leading to dose interruption possibly related to treatment	62 Participants
Number of Participants With Treatment Emergent Adverse Events (AEs) Any AE leading to dose reduction possibly related to treatment	60 Participants

Adverse Events

Adavosertib

Serious events: 53 serious events

Other events: 109 other events

Deaths: 47 deaths

Serious adverse events

Measure	Adavosertib n=109 participants at risk Participants received adavosertib 300 mg administered orally, once daily on Days 1 to 5 followed by 2 days off and Days 8 to 12 (21 days treatment cycle).
Injury, poisoning and procedural complications Spinal fracture	0.92% 1/109 • Number of events 1 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Infections and infestations Biliary sepsis	0.92% 1/109 • Number of events 1 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Infections and infestations Escherichia sepsis	0.92% 1/109 • Number of events 1 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Infections and infestations Infectious pleural effusion	0.92% 1/109 • Number of events 1 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Infections and infestations Kidney Infection	0.92% 1/109 • Number of events 1 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Infections and infestations Sepsis	4.6% 5/109 • Number of events 5 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Blood and lymphatic system disorders Anaemia	2.8% 3/109 • Number of events 3 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Blood and lymphatic system disorders Neutropenia	3.7% 4/109 • Number of events 4 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Blood and lymphatic system disorders Thrombocytopenia	1.8% 2/109 • Number of events 2 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Metabolism and nutrition disorders Dehydration	0.92% 1/109 • Number of events 1 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Metabolism and nutrition disorders Electrolyte imbalance	0.92% 1/109 • Number of events 1 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Nervous system disorders Cerebrovascular accident	1.8% 2/109 • Number of events 2 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Nervous system disorders Epilepsy	0.92% 1/109 • Number of events 1 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Nervous system disorders Intracranial aneurysm	0.92% 1/109 • Number of events 1 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Nervous system disorders Subarachnoid haemorrhage	0.92% 1/109 • Number of events 1 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Nervous system disorders Syncope	1.8% 2/109 • Number of events 2 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Nervous system disorders Transient ischaemic attack	0.92% 1/109 • Number of events 1 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Cardiac disorders Atrial fibrillation	0.92% 1/109 • Number of events 1 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Cardiac disorders Cardiac disorder	0.92% 1/109 • Number of events 1 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Cardiac disorders Sinus tachycardia	0.92% 1/109 • Number of events 1 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Vascular disorders Embolism	2.8% 3/109 • Number of events 3 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Vascular disorders Haematoma	0.92% 1/109 • Number of events 1 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Vascular disorders Hypertensive crisis	0.92% 1/109 • Number of events 1 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Vascular disorders Hypotension	1.8% 2/109 • Number of events 2 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.92% 1/109 • Number of events 1 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Respiratory, thoracic and mediastinal disorders Dyspnoea	3.7% 4/109 • Number of events 5 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.92% 1/109 • Number of events 1 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Respiratory, thoracic and mediastinal disorders Pleural effusion	1.8% 2/109 • Number of events 2 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.92% 1/109 • Number of events 1 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	5.5% 6/109 • Number of events 6 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.92% 1/109 • Number of events 1 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Gastrointestinal disorders Abdominal pain	1.8% 2/109 • Number of events 2 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Gastrointestinal disorders Abdominal pain lower	0.92% 1/109 • Number of events 1 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Gastrointestinal disorders Constipation	0.92% 1/109 • Number of events 1 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Gastrointestinal disorders Diarrhoea	3.7% 4/109 • Number of events 4 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Gastrointestinal disorders Duodenal ulcer	0.92% 1/109 • Number of events 1 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Gastrointestinal disorders Gastritis	0.92% 1/109 • Number of events 1 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Gastrointestinal disorders Large intestinal obstruction	0.92% 1/109 • Number of events 1 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Gastrointestinal disorders Large intestine perforation	0.92% 1/109 • Number of events 1 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Gastrointestinal disorders Nausea	0.92% 1/109 • Number of events 1 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Gastrointestinal disorders Rectal haemorrhage	0.92% 1/109 • Number of events 1 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Gastrointestinal disorders Small intestinal obstruction	0.92% 1/109 • Number of events 1 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Gastrointestinal disorders Vomiting	4.6% 5/109 • Number of events 6 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Musculoskeletal and connective tissue disorders Back pain	0.92% 1/109 • Number of events 1 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Musculoskeletal and connective tissue disorders Muscular weakness	1.8% 2/109 • Number of events 3 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Renal and urinary disorders Acute kidney injury	1.8% 2/109 • Number of events 2 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Renal and urinary disorders Haematuria	0.92% 1/109 • Number of events 1 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Renal and urinary disorders Urinary retention	0.92% 1/109 • Number of events 1 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
General disorders Fatigue	2.8% 3/109 • Number of events 3 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
General disorders Gait disturbance	0.92% 1/109 • Number of events 1 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
General disorders General physical health deterioration	0.92% 1/109 • Number of events 1 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
General disorders Generalised oedema	0.92% 1/109 • Number of events 1 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
General disorders Malaise	0.92% 1/109 • Number of events 1 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
General disorders Oedema	0.92% 1/109 • Number of events 1 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
General disorders Oedema peripheral	0.92% 1/109 • Number of events 1 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
General disorders Pyrexia	0.92% 1/109 • Number of events 2 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Investigations Alanine aminotransferase increased	0.92% 1/109 • Number of events 1 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Investigations Lymphocyte count decreased	0.92% 1/109 • Number of events 1 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Investigations Neutrophil count decreased	3.7% 4/109 • Number of events 4 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Investigations Platelet count decreased	0.92% 1/109 • Number of events 1 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Injury, poisoning and procedural complications Fall	0.92% 1/109 • Number of events 1 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.

Other adverse events

Measure	Adavosertib n=109 participants at risk Participants received adavosertib 300 mg administered orally, once daily on Days 1 to 5 followed by 2 days off and Days 8 to 12 (21 days treatment cycle).
Infections and infestations Urinary tract infection	14.7% 16/109 • Number of events 19 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Blood and lymphatic system disorders Anaemia	67.9% 74/109 • Number of events 155 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Blood and lymphatic system disorders Leukopenia	7.3% 8/109 • Number of events 15 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Blood and lymphatic system disorders Neutropenia	23.9% 26/109 • Number of events 48 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Blood and lymphatic system disorders Thrombocytopenia	24.8% 27/109 • Number of events 40 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Metabolism and nutrition disorders Decreased appetite	24.8% 27/109 • Number of events 39 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Metabolism and nutrition disorders Hyperglycaemia	16.5% 18/109 • Number of events 21 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Metabolism and nutrition disorders Hypoalbuminaemia	9.2% 10/109 • Number of events 18 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Metabolism and nutrition disorders Hypokalaemia	19.3% 21/109 • Number of events 27 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Metabolism and nutrition disorders Hypomagnesaemia	15.6% 17/109 • Number of events 27 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Metabolism and nutrition disorders Hyponatraemia	9.2% 10/109 • Number of events 11 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Psychiatric disorders Insomnia	8.3% 9/109 • Number of events 9 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Nervous system disorders Dizziness	10.1% 11/109 • Number of events 17 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Nervous system disorders Dysgeusia	15.6% 17/109 • Number of events 19 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Nervous system disorders Headache	12.8% 14/109 • Number of events 19 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Vascular disorders Hypertension	13.8% 15/109 • Number of events 22 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Respiratory, thoracic and mediastinal disorders Cough	5.5% 6/109 • Number of events 8 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Respiratory, thoracic and mediastinal disorders Dyspnoea	17.4% 19/109 • Number of events 21 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Respiratory, thoracic and mediastinal disorders Pneumonitis	5.5% 6/109 • Number of events 6 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Gastrointestinal disorders Abdominal distension	9.2% 10/109 • Number of events 11 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Gastrointestinal disorders Abdominal pain	31.2% 34/109 • Number of events 45 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Gastrointestinal disorders Abdominal pain upper	14.7% 16/109 • Number of events 22 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Gastrointestinal disorders Constipation	41.3% 45/109 • Number of events 58 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Gastrointestinal disorders Diarrhoea	67.0% 73/109 • Number of events 146 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Gastrointestinal disorders Dyspepsia	11.9% 13/109 • Number of events 13 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Gastrointestinal disorders Gastrooesophageal reflux disease	7.3% 8/109 • Number of events 8 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Gastrointestinal disorders Nausea	65.1% 71/109 • Number of events 140 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Gastrointestinal disorders Vomiting	35.8% 39/109 • Number of events 55 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Musculoskeletal and connective tissue disorders Arthralgia	14.7% 16/109 • Number of events 20 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Musculoskeletal and connective tissue disorders Back pain	11.0% 12/109 • Number of events 12 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Musculoskeletal and connective tissue disorders Muscular weakness	5.5% 6/109 • Number of events 9 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Musculoskeletal and connective tissue disorders Myalgia	6.4% 7/109 • Number of events 7 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Renal and urinary disorders Dysuria	5.5% 6/109 • Number of events 6 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Renal and urinary disorders Pollakiuria	6.4% 7/109 • Number of events 7 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
General disorders Asthenia	41.3% 45/109 • Number of events 72 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
General disorders Fatigue	39.4% 43/109 • Number of events 66 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
General disorders Non-cardiac chest pain	5.5% 6/109 • Number of events 6 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
General disorders Oedema peripheral	18.3% 20/109 • Number of events 26 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
General disorders Pyrexia	6.4% 7/109 • Number of events 8 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Investigations Alanine aminotransferase increased	25.7% 28/109 • Number of events 39 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Investigations Aspartate aminotransferase increased	21.1% 23/109 • Number of events 31 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Investigations Blood alkaline phosphatase increased	12.8% 14/109 • Number of events 18 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Investigations Blood creatinine increased	24.8% 27/109 • Number of events 40 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Investigations Lymphocyte count decreased	5.5% 6/109 • Number of events 9 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Investigations Neutrophil count decreased	14.7% 16/109 • Number of events 31 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Investigations Platelet count decreased	20.2% 22/109 • Number of events 40 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Investigations Weight decreased	11.0% 12/109 • Number of events 16 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.
Injury, poisoning and procedural complications Fall	5.5% 6/109 • Number of events 6 • From baseline to post-treatment follow-up (30 days after last dose), approximately up to 114 weeks All adverse events during the trial are reported.

Additional Information

Global Clinical Head

AstraZeneca Clinical Study Information Centre

Phone: +1-877-240-94 79

Email: information.center@astrazeneca.com

Results disclosure agreements

• Principal investigator is a sponsor employee This document contains trade secrets and confidential commercial information, disclosure of which is prohibited without providing advance notice to AstraZeneca and opportunity to object.
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