Trial Outcomes & Findings for Phase Ib Study AZD1775 in Combination With Carboplatin and Paclitaxel in Adult Asian Patients With Solid Tumours (NCT NCT02341456)

NCT ID: NCT02341456

Last Updated: 2019-03-25

Results Overview

The number of patients with treatment-emergent adverse events was analyzed on the safety analysis set which was comprised of all patients who received at least one dose of the investigational drug.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 19 participants
• Primary outcome timeframe: Up to 21 days (1 Cycle)
• Results posted on: 2019-03-25

Participant Flow

The study was conducted at 7 clinical investigational sites located in Australia (2), Japan (2), and South Korea (3). A total of 21 subjects consented and 19 were enrolled between January 14, 2015 and June 13, 2016.

Total 21 subjects were consented to participate in the study. One (1) subject was screen failure, and one (1) other subject withdrew prior to treatment; Nineteen (19) subjects received treatment under the protocol.

Participant milestones

Measure	Cohort 1 Subjects in Cohort 1 received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 1a Subjects in Cohort 1a received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 2 Subjects in Cohort 2 received a single oral dose of 225 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 225 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.
Overall Study STARTED	7	6	6
Overall Study COMPLETED	3	0	2
Overall Study NOT COMPLETED	4	6	4

Reasons for withdrawal

Measure	Cohort 1 Subjects in Cohort 1 received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 1a Subjects in Cohort 1a received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 2 Subjects in Cohort 2 received a single oral dose of 225 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 225 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.
Overall Study Disease progression	2	3	1
Overall Study Death	1	1	1
Overall Study Withdrawal by Subject	0	1	1
Overall Study Moved to local access programme.	0	1	1
Overall Study Physician Decision	1	0	0

Baseline Characteristics

Phase Ib Study AZD1775 in Combination With Carboplatin and Paclitaxel in Adult Asian Patients With Solid Tumours

Baseline characteristics by cohort

Measure	Cohort 1 n=7 Participants Subjects in Cohort 1 received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 1a n=6 Participants Subjects in Cohort 1a received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 2 n=6 Participants Subjects in Cohort 2 received a single oral dose of 225 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 225 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Total n=19 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	7 Participants n=5 Participants	6 Participants n=7 Participants	5 Participants n=5 Participants	18 Participants n=4 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Age, Continuous	55.0 years STANDARD_DEVIATION 5.23 • n=5 Participants	43.0 years STANDARD_DEVIATION 14.10 • n=7 Participants	52.2 years STANDARD_DEVIATION 13.82 • n=5 Participants	50.3 years STANDARD_DEVIATION 12.04 • n=4 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants	11 Participants n=4 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	8 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	7 Participants n=5 Participants	6 Participants n=7 Participants	6 Participants n=5 Participants	19 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized Asian	7 Participants n=5 Participants	6 Participants n=7 Participants	6 Participants n=5 Participants	19 Participants n=4 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Region of Enrollment Australia	2 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Region of Enrollment Japan	3 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	7 Participants n=4 Participants
Region of Enrollment Korea, Republic Of	2 Participants n=5 Participants	5 Participants n=7 Participants	5 Participants n=5 Participants	12 Participants n=4 Participants
Smoking History Never Used Tobacco	4 Participants n=5 Participants	4 Participants n=7 Participants	3 Participants n=5 Participants	11 Participants n=4 Participants
Smoking History Former Smoker	3 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	7 Participants n=4 Participants
Smoking History Current Smoker	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Cancer Diagnosis Head and Neck	2 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Cancer Diagnosis Other; Gallbladder	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Cancer Diagnosis Stomach	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Cancer Diagnosis Cervix	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Cancer Diagnosis Ovary	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Cancer Diagnosis Uterus	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Cancer Diagnosis Breast	0 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants	4 Participants n=4 Participants
Cancer Diagnosis Pancreas	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Cancer Diagnosis Other; Thymic	0 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Cancer Diagnosis Skin/Soft Tissue	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Cancer Diagnosis Lung	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Type of Tobacco Product Used Cigarettes	3 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants	8 Participants n=4 Participants
Type of Tobacco Product Used Cigars	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Type of Tobacco Product Used Cigarillo	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Type of Tobacco Product Used No history of tobacco use	4 Participants n=5 Participants	4 Participants n=7 Participants	3 Participants n=5 Participants	11 Participants n=4 Participants

PRIMARY outcome

Timeframe: Up to 21 days (1 Cycle)

Population: All patients who received at least one dose of the investigational drug.

The number of patients with treatment-emergent adverse events was analyzed on the safety analysis set which was comprised of all patients who received at least one dose of the investigational drug.

Outcome measures

Measure	Cohort 1 n=7 Participants Subjects in Cohort 1 received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 1a n=6 Participants Subjects in Cohort 1a received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 2 n=6 Participants Subjects in Cohort 2 received a single oral dose of 225 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 225 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.
Number of Patients With Treatment-Emergent Adverse Events Patients with ≥ 1 Adverse Event (AE)	7 Participants	6 Participants	6 Participants
Number of Patients With Treatment-Emergent Adverse Events Patients with ≥ 1 Treatment-Emergent AE (TEAE)	6 Participants	6 Participants	6 Participants
Number of Patients With Treatment-Emergent Adverse Events Patients with TEAE Related to Treatment	6 Participants	4 Participants	6 Participants
Number of Patients With Treatment-Emergent Adverse Events Patients with Serious TEAE	3 Participants	0 Participants	4 Participants
Number of Patients With Treatment-Emergent Adverse Events Patients with Severe TEAE	6 Participants	4 Participants	6 Participants
Number of Patients With Treatment-Emergent Adverse Events Patients with TEAE with AZD1775 discontinued	1 Participants	0 Participants	2 Participants
Number of Patients With Treatment-Emergent Adverse Events Patients with TEAE with paclitaxel discontinued	1 Participants	NA Participants Patients in Cohort 1a did not receive paclitaxel.	2 Participants
Number of Patients With Treatment-Emergent Adverse Events Patients with TEAE with carboplatin discontinued	0 Participants	0 Participants	2 Participants
Number of Patients With Treatment-Emergent Adverse Events Patients with TEAE and fatal outcome	1 Participants	0 Participants	1 Participants
Number of Patients With Treatment-Emergent Adverse Events Patients with Dose-Limiting Toxicity	1 Participants	1 Participants	2 Participants

PRIMARY outcome

Timeframe: Up to 21 days (1 Cycle)

Population: All patients who received at least one dose of the investigational drug.

The number of treatment-emergent adverse events was counted in the safety analysis set which was comprised of all patients who received at least one dose of the investigational drug.

Outcome measures

Measure	Cohort 1 n=7 Participants Subjects in Cohort 1 received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 1a n=6 Participants Subjects in Cohort 1a received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 2 n=6 Participants Subjects in Cohort 2 received a single oral dose of 225 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 225 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.
Number of Treatment-Emergent Adverse Events (TEAE) Number of Adverse Events (AEs)	370 TEAE	202 TEAE	382 TEAE
Number of Treatment-Emergent Adverse Events (TEAE) Number of TEAEs	362 TEAE	182 TEAE	381 TEAE
Number of Treatment-Emergent Adverse Events (TEAE) Number of TEAEs Related to Study Treatment	262 TEAE	95 TEAE	263 TEAE
Number of Treatment-Emergent Adverse Events (TEAE) Number of Serious TEAEs	9 TEAE	0 TEAE	9 TEAE
Number of Treatment-Emergent Adverse Events (TEAE) Number of Severe TEAEs	88 TEAE	23 TEAE	101 TEAE
Number of Treatment-Emergent Adverse Events (TEAE) Number of TEAEs with AZD1775 discontinued	3 TEAE	0 TEAE	3 TEAE
Number of Treatment-Emergent Adverse Events (TEAE) Number of TEAEs with paclitaxel discontinued	1 TEAE	NA TEAE Patients in Cohort 1a did not receive paclitaxel.	3 TEAE
Number of Treatment-Emergent Adverse Events (TEAE) Number of TEAEs with carboplatin discontinued	0 TEAE	0 TEAE	3 TEAE
Number of Treatment-Emergent Adverse Events (TEAE) Number of TEAEs with fatal outcome	1 TEAE	0 TEAE	2 TEAE
Number of Treatment-Emergent Adverse Events (TEAE) Number of Dose-Limiting Toxicities (DLT)	1 TEAE	1 TEAE	2 TEAE
Number of Treatment-Emergent Adverse Events (TEAE) Number of TEAEs with DLT	1 TEAE	1 TEAE	2 TEAE

PRIMARY outcome

Timeframe: Up to 1 week

Population: All patients who received at least one dose of the investigational drug.

The number of patients with TEAEs during AZD1775 Monotherapy Cycle was analyzed in the safety analysis set which was comprised of all patients who received at least one dose of the investigational drug.

Outcome measures

Measure	Cohort 1 n=7 Participants Subjects in Cohort 1 received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 1a n=6 Participants Subjects in Cohort 1a received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 2 n=6 Participants Subjects in Cohort 2 received a single oral dose of 225 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 225 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.
Number of Patients With Treatment-Emergent Adverse Events During AZD1775 Monotherapy Cycle by System Organ Class and Preferred Term Patients with at least 1 TEAE in AZD1775 cycle	1 Participants	1 Participants	2 Participants
Number of Patients With Treatment-Emergent Adverse Events During AZD1775 Monotherapy Cycle by System Organ Class and Preferred Term Gastrointestinal Disorders - Nausea	1 Participants	1 Participants	1 Participants
Number of Patients With Treatment-Emergent Adverse Events During AZD1775 Monotherapy Cycle by System Organ Class and Preferred Term Gastrointestinal Disorders - Constipation	0 Participants	0 Participants	1 Participants
Number of Patients With Treatment-Emergent Adverse Events During AZD1775 Monotherapy Cycle by System Organ Class and Preferred Term Gastrointestinal Disorders - Diarrhoea	0 Participants	1 Participants	0 Participants
Number of Patients With Treatment-Emergent Adverse Events During AZD1775 Monotherapy Cycle by System Organ Class and Preferred Term Immune System Disorders - Hypersensitivity	0 Participants	0 Participants	1 Participants

PRIMARY outcome

Timeframe: Up to 21 days (1 Cycle)

Population: All patients who received at least one dose of the investigational drug.

The number of patients with clinically important changes in haematology and coagulation TEAEs was analyzed in the safety analysis set which was comprised of all patients who received at least one dose of the investigational drug.

Outcome measures

Measure	Cohort 1 n=7 Participants Subjects in Cohort 1 received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 1a n=6 Participants Subjects in Cohort 1a received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 2 n=6 Participants Subjects in Cohort 2 received a single oral dose of 225 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 225 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.
Number of Patients With Clinically Important Changes in Haematology and Coagulation TEAEs by System Organ Class and Preferred Term Blood & Lymphatic System Disorders (BLSD) Anaemia	6 Participants	4 Participants	5 Participants
Number of Patients With Clinically Important Changes in Haematology and Coagulation TEAEs by System Organ Class and Preferred Term BLSD - Neutropenia	3 Participants	0 Participants	2 Participants
Number of Patients With Clinically Important Changes in Haematology and Coagulation TEAEs by System Organ Class and Preferred Term BLSD - Thrombocytopenia	1 Participants	1 Participants	2 Participants
Number of Patients With Clinically Important Changes in Haematology and Coagulation TEAEs by System Organ Class and Preferred Term BLSD - Febrile Neutropenia	1 Participants	0 Participants	2 Participants
Number of Patients With Clinically Important Changes in Haematology and Coagulation TEAEs by System Organ Class and Preferred Term Investigations - WBC Count Decreased	5 Participants	3 Participants	5 Participants
Number of Patients With Clinically Important Changes in Haematology and Coagulation TEAEs by System Organ Class and Preferred Term Investigations - Neutrophil Count Decreased	3 Participants	4 Participants	3 Participants
Number of Patients With Clinically Important Changes in Haematology and Coagulation TEAEs by System Organ Class and Preferred Term Investigations - Platelet Count Decreased	4 Participants	3 Participants	3 Participants
Number of Patients With Clinically Important Changes in Haematology and Coagulation TEAEs by System Organ Class and Preferred Term Investigations - Haematocrit Decreased	1 Participants	0 Participants	0 Participants
Number of Patients With Clinically Important Changes in Haematology and Coagulation TEAEs by System Organ Class and Preferred Term Investigations - Monocyte Count Decreased	1 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Up to 21 days (1 Cycle)

Population: All patients who received at least one dose of the investigational drug.

The number of patients with clinically important changes in clinical chemistry TEAEs was analyzed in the safety analysis set which was comprised of all patients who received at least one dose of the investigational drug.

Outcome measures

Measure	Cohort 1 n=7 Participants Subjects in Cohort 1 received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 1a n=6 Participants Subjects in Cohort 1a received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 2 n=6 Participants Subjects in Cohort 2 received a single oral dose of 225 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 225 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.
Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term Aspartate aminotransferase increased	0 Participants	2 Participants	1 Participants
Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term Alanine aminotransferase increased	0 Participants	1 Participants	0 Participants
Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term Blood alkaline phosphatase increased	1 Participants	0 Participants	0 Participants
Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term Blood lactate dehydrogenase increased	1 Participants	0 Participants	0 Participants
Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term C-reactive protein increased	1 Participants	0 Participants	0 Participants
Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term Hypoalbuminemia	2 Participants	0 Participants	2 Participants
Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term Hypokalemia	1 Participants	1 Participants	2 Participants
Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term Hypophosphatemia	1 Participants	0 Participants	2 Participants
Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term Dehydration	1 Participants	0 Participants	1 Participants
Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term Hyperglycaemia	2 Participants	0 Participants	0 Participants
Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term Hypocalcaemia	0 Participants	0 Participants	1 Participants
Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term Hyponatraemia	1 Participants	0 Participants	1 Participants
Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term Hypercalcaemia	0 Participants	0 Participants	1 Participants
Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term Hypercholsterolaemia	0 Participants	0 Participants	1 Participants
Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term Hypoglycaemia	1 Participants	0 Participants	0 Participants
Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term Hypomagnesaemia	0 Participants	0 Participants	1 Participants
Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term Azotemia	1 Participants	0 Participants	0 Participants
Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term Hepatic function abnormal	1 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Up to 21 days (1 Cycle)

Population: All patients who received at least one dose of the investigational drug.

The number of patients with clinically important changes in vital sign TEAEs was analyzed in the safety analysis set which was comprised of all patients who received at least one dose of the investigational drug.

Outcome measures

Measure	Cohort 1 n=7 Participants Subjects in Cohort 1 received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 1a n=6 Participants Subjects in Cohort 1a received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 2 n=6 Participants Subjects in Cohort 2 received a single oral dose of 225 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 225 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.
Number of Patients With Clinically Important Abnormalities in Vital Signs by Preferred Term Pyrexia	3 Participants	1 Participants	4 Participants
Number of Patients With Clinically Important Abnormalities in Vital Signs by Preferred Term Hypotension	2 Participants	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Up to 18 months

Population: Best overall response was analyzed in the Evaluable-for-Response set, comprised of all patients who received at least one dose of the investigational drug and who had measurable disease at baseline.

The number of subjects with best overall response in CR, PR, NE, SD, PD subcategory. Best overall response is calculated based on the overall visit responses from each RECIST assessment.

Outcome measures

Measure	Cohort 1 n=6 Participants Subjects in Cohort 1 received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 1a n=6 Participants Subjects in Cohort 1a received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 2 n=6 Participants Subjects in Cohort 2 received a single oral dose of 225 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 225 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.
Best Overall Response Partial Response	1 Participants	1 Participants	3 Participants
Best Overall Response Not Evaluable	1 Participants	2 Participants	1 Participants
Best Overall Response Stable Disease	2 Participants	2 Participants	2 Participants
Best Overall Response Progressive Disease	2 Participants	1 Participants	0 Participants
Best Overall Response Complete Response	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 18 months

Objective response is defined as either a complete response or a partial response.

Outcome measures

Measure	Cohort 1 n=6 Participants Subjects in Cohort 1 received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 1a n=6 Participants Subjects in Cohort 1a received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 2 n=6 Participants Subjects in Cohort 2 received a single oral dose of 225 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 225 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.
Number of Patients With an Objective Response	1 Participants	1 Participants	3 Participants

SECONDARY outcome

Timeframe: Up to 18 months

Objective response is defined as either a complete response or a partial response.

Outcome measures

Measure	Cohort 1 n=6 Participants Subjects in Cohort 1 received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 1a n=6 Participants Subjects in Cohort 1a received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 2 n=6 Participants Subjects in Cohort 2 received a single oral dose of 225 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 225 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.
Percentage of Patients With an Objective Response	16.7 Percentage Interval 0.4 to 64.1	16.7 Percentage Interval 0.4 to 64.1	50 Percentage Interval 11.8 to 88.2

SECONDARY outcome

Timeframe: Up to 18 months

Clinical benefit is defined as achieving complete response, partial response, or stable disease.

Outcome measures

Measure	Cohort 1 n=6 Participants Subjects in Cohort 1 received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 1a n=6 Participants Subjects in Cohort 1a received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 2 n=6 Participants Subjects in Cohort 2 received a single oral dose of 225 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 225 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.
Number of Patients With Clinical Benefit	3 Participants	3 Participants	5 Participants

SECONDARY outcome

Timeframe: Up to 18 months

Clinical benefit is defined as achieving complete response, partial response, or stable disease.

Outcome measures

Measure	Cohort 1 n=6 Participants Subjects in Cohort 1 received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 1a n=6 Participants Subjects in Cohort 1a received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 2 n=6 Participants Subjects in Cohort 2 received a single oral dose of 225 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 225 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.
Percentage of Patients With Clinical Benefit	50 Percentage Interval 11.8 to 88.2	50 Percentage Interval 11.8 to 88.2	83.3 Percentage Interval 35.9 to 99.6

SECONDARY outcome

Timeframe: Up to 18 months

The duration of response is defined as the time in weeks from the date of first documented overall response occurrence of CR or PR, (whichever was recorded first) to the earliest date that progressive disease/death was documented. If progression or death has not been documented, a patient's DoR was censored at the date of last tumour assessment.

Outcome measures

Measure	Cohort 1 n=6 Participants Subjects in Cohort 1 received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 1a n=6 Participants Subjects in Cohort 1a received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 2 n=6 Participants Subjects in Cohort 2 received a single oral dose of 225 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 225 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.
Duration of Response	18.1 Weeks Interval 0.0 to 9999.9	0.00 Weeks Interval 0.0 to 9999.9	20.7 Weeks Interval 0.0 to 9999.9

SECONDARY outcome

Timeframe: PK Samples collected in all treatment groups on Cycle 0 Day 1, Cycle 1 Day 1, and Cycle 1 Day 3 before the first (morning) dose of AZD1775 (predose) and at 1, 2, 4, 6, and 8 hours postdose

Population: The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained.

Outcome measures

Measure	Cohort 1 n=6 Participants Subjects in Cohort 1 received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 1a n=4 Participants Subjects in Cohort 1a received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 2 n=6 Participants Subjects in Cohort 2 received a single oral dose of 225 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 225 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.
Peak Plasma Concentration (Cmax) of AZD1775 Following Single Dose Administration of AZD1775 Monotherapy	689.1 nM Geometric Coefficient of Variation 51.79	649.2 nM Geometric Coefficient of Variation 10.74	1066 nM Geometric Coefficient of Variation 38

SECONDARY outcome

Timeframe: PK Samples will be collected in all treatment groups on Cycle 0 Day 1, Cycle 1 Day 1, and Cycle 1 Day 3 before the first (morning) dose of AZD1775 (predose) and at 1, 2, 4, 6, and 8 hours postdose

Population: The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained.

Outcome measures

Measure	Cohort 1 n=7 Participants Subjects in Cohort 1 received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 1a n=5 Participants Subjects in Cohort 1a received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 2 n=6 Participants Subjects in Cohort 2 received a single oral dose of 225 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 225 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.
Time to Maximum Plasma Concentration (Tmax) of AZD1775 Following Single Dose Administration of AZD1775 Monotherapy	2.02 hours Interval 1.0 to 8.0	3.95 hours Interval 2.0 to 8.0	3.96 hours Interval 1.0 to 5.87

SECONDARY outcome

Timeframe: PK Samples will be collected in all treatment groups on Cycle 0 Day 1, Cycle 1 Day 1, and Cycle 1 Day 3 before the first (morning) dose of AZD1775 (predose) and at 1, 2, 4, 6, and 8 hours postdose

Population: The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained.

Outcome measures

Measure	Cohort 1 n=6 Participants Subjects in Cohort 1 received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 1a n=4 Participants Subjects in Cohort 1a received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 2 n=6 Participants Subjects in Cohort 2 received a single oral dose of 225 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 225 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.
Area Under the Plasma Concentration-time Curve From Zero to the Time of the Last Measurable Concentration (AUC0-t) Following Single Dose Administration of AZD1775 Monotherapy	3521 nM*h Geometric Coefficient of Variation 44.91	3387 nM*h Geometric Coefficient of Variation 12.54	5331 nM*h Geometric Coefficient of Variation 37.42

SECONDARY outcome

Timeframe: PK Samples will be collected in all treatment groups on Cycle 0 Day 1, Cycle 1 Day 1, and Cycle 1 Day 3 before the first (morning) dose of AZD1775 (predose) and at 1, 2, 4, 6, and 8 hours postdose

Population: The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained.

Outcome measures

Measure	Cohort 1 n=6 Participants Subjects in Cohort 1 received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 1a n=4 Participants Subjects in Cohort 1a received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 2 n=6 Participants Subjects in Cohort 2 received a single oral dose of 225 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 225 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.
Plasma Concentration of AZD1775 8 Hours After Single Dose Administration (C8h) of AZD1775 Monotherapy	370.1 nM Geometric Coefficient of Variation 29.15	343.5 nM Geometric Coefficient of Variation 29.97	612 nM Geometric Coefficient of Variation 36.6

SECONDARY outcome

Timeframe: AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion

Population: The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained.

Outcome measures

Measure	Cohort 1 n=5 Participants Subjects in Cohort 1 received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 1a n=5 Participants Subjects in Cohort 1a received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 2 n=6 Participants Subjects in Cohort 2 received a single oral dose of 225 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 225 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.
Peak Plasma Concentration (Cmax) of AZD1775 Following Oral Dose of AZD1775 in Combination With IV Infusion of Paclitaxel and Carboplatin (Cohorts 1 and 2) or Carboplatin Alone (Cohort 1a)	705.4 nM Geometric Coefficient of Variation 28.03	654.8 nM Geometric Coefficient of Variation 32.27	1133 nM Geometric Coefficient of Variation 16.3

SECONDARY outcome

Timeframe: AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion

Population: The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained.

Outcome measures

Measure	Cohort 1 n=6 Participants Subjects in Cohort 1 received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 1a n=6 Participants Subjects in Cohort 1a received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 2 n=6 Participants Subjects in Cohort 2 received a single oral dose of 225 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 225 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.
Time to Maximum Plasma Concentration (Tmax) of AZD1775 Following Single Dose of AZD1775 in Combination With IV Paclitaxel and Carboplatin (Cohorts 1 and 2) or Carboplatin Alone (Cohort 1a)	4.00 hours Interval 0.95 to 8.02	4.04 hours Interval 3.98 to 6.0	4.00 hours Interval 2.05 to 4.08

SECONDARY outcome

Timeframe: AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion

Population: The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained.

Outcome measures

Measure	Cohort 1 n=5 Participants Subjects in Cohort 1 received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 1a n=5 Participants Subjects in Cohort 1a received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 2 n=6 Participants Subjects in Cohort 2 received a single oral dose of 225 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 225 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.
Area Under the Plasma Concentration-time Curve From Zero to the Time of the Last Measurable Concentration (AUC0-t) Following Single Dose of AZD1775 in Combination With IV Paclitaxel and Carboplatin (Cohorts 1 and 2) or Carboplatin Alone (Cohort 1a)	4191 nM*h Geometric Coefficient of Variation 34.89	2902 nM*h Geometric Coefficient of Variation 33.21	5606 nM*h Geometric Coefficient of Variation 20.02

SECONDARY outcome

Timeframe: AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion

Population: The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained.

Outcome measures

Measure	Cohort 1 n=6 Participants Subjects in Cohort 1 received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 1a n=6 Participants Subjects in Cohort 1a received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 2 n=6 Participants Subjects in Cohort 2 received a single oral dose of 225 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 225 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.
Plasma Concentration of AZD1775 8 Hours After Single Dose Administration (C8h) of AZD1775 in Combination With IV Paclitaxel and Carboplatin (Cohorts 1 and 2) or Carboplatin Alone (Cohort 1a)	444.6 nM Geometric Coefficient of Variation 27.83	378.2 nM Geometric Coefficient of Variation 27.61	805.9 nM Geometric Coefficient of Variation 27.5

SECONDARY outcome

Timeframe: AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion

Population: The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained.

Outcome measures

Measure	Cohort 1 n=6 Participants Subjects in Cohort 1 received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 1a n=6 Participants Subjects in Cohort 1a received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 2 n=5 Participants Subjects in Cohort 2 received a single oral dose of 225 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 225 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.
Peak Plasma Concentration (Cmax) of AZD1775 at Steady State When Given in Combination With IV Infusion of Paclitaxel and Carboplatin (Cohorts 1 and 2) or Carboplatin Alone (Cohort 1a)	1271 nM Geometric Coefficient of Variation 30.52	1129 nM Geometric Coefficient of Variation 25.51	2289 nM Geometric Coefficient of Variation 32.82

SECONDARY outcome

Timeframe: AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion

Population: The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained.

Outcome measures

Measure	Cohort 1 n=6 Participants Subjects in Cohort 1 received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 1a n=6 Participants Subjects in Cohort 1a received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 2 n=6 Participants Subjects in Cohort 2 received a single oral dose of 225 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 225 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.
Time to Maximum Plasma Concentration (Tmax) of AZD1775 at Steady State When Given in Combination With IV Paclitaxel and Carboplatin (Cohorts 1 and 2) or Carboplatin Alone (Cohort 1a)	4.00 hours Interval 2.05 to 4.08	3.09 hours Interval 1.95 to 4.08	4.04 hours Interval 1.0 to 7.95

SECONDARY outcome

Timeframe: AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion

Population: The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained.

Outcome measures

Measure	Cohort 1 n=6 Participants Subjects in Cohort 1 received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 1a n=6 Participants Subjects in Cohort 1a received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 2 n=5 Participants Subjects in Cohort 2 received a single oral dose of 225 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 225 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.
Area Under the Plasma Concentration-time Curve From Zero to the Time of the Last Measurable Concentration (AUC0-t) at Steady State for AZD1775 in Combination With IV Paclitaxel and Carboplatin (Cohorts 1 and 2) or Carboplatin Alone (Cohort 1a)	8300 nM*h Geometric Coefficient of Variation 32.85	7154 nM*h Geometric Coefficient of Variation 32.29	14870 nM*h Geometric Coefficient of Variation 34.05

SECONDARY outcome

Timeframe: AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion

Population: The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained.

Outcome measures

Measure	Cohort 1 n=6 Participants Subjects in Cohort 1 received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 1a n=6 Participants Subjects in Cohort 1a received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 2 n=6 Participants Subjects in Cohort 2 received a single oral dose of 225 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 225 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.
Plasma Concentration of AZD1775 8 Hours After Administration (C8h) at Steady State in Combination With IV Paclitaxel and Carboplatin (Cohorts 1 and 2) or Carboplatin Alone (Cohort 1a)	982 nM Geometric Coefficient of Variation 30.17	774.6 nM Geometric Coefficient of Variation 32.96	1700 nM Geometric Coefficient of Variation 37.6

SECONDARY outcome

Timeframe: AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion

Population: The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained.

Outcome measures

Measure	Cohort 1 n=6 Participants Subjects in Cohort 1 received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 1a Subjects in Cohort 1a received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 2 n=4 Participants Subjects in Cohort 2 received a single oral dose of 225 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 225 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.
Peak Plasma Concentration (Cmax) of Paclitaxel Following Single IV Infusion in Combination With Single Dose Oral AZD1775 and IV Carboplatin	4848 ng/mL Geometric Coefficient of Variation 31.13	—	5361 ng/mL Geometric Coefficient of Variation 4.744

SECONDARY outcome

Timeframe: AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion

Population: The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained.

Outcome measures

Measure	Cohort 1 n=6 Participants Subjects in Cohort 1 received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 1a Subjects in Cohort 1a received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 2 n=4 Participants Subjects in Cohort 2 received a single oral dose of 225 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 225 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.
Area Under the Plasma Concentration-time Curve (AUC0-t) of Paclitaxel Following Single IV Infusion in Combination With Single Dose Oral AZD1775 and IV Carboplatin	13100 h*ng/mL Geometric Coefficient of Variation 36.11	—	16360 h*ng/mL Geometric Coefficient of Variation 20.11

SECONDARY outcome

Timeframe: AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion

Population: The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained.

Outcome measures

Measure	Cohort 1 n=6 Participants Subjects in Cohort 1 received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 1a Subjects in Cohort 1a received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 2 n=4 Participants Subjects in Cohort 2 received a single oral dose of 225 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 225 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.
Plasma Concentration of Paclitaxel at the End of Infusion (Ceoi) When Given Combination With Oral AZD1775 and IV Carboplatin.	4791 ng/mL Geometric Coefficient of Variation 32.33	—	5361 ng/mL Geometric Coefficient of Variation 4.744

SECONDARY outcome

Timeframe: AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion

Population: The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained.

Outcome measures

Measure	Cohort 1 n=6 Participants Subjects in Cohort 1 received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 1a Subjects in Cohort 1a received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 2 n=4 Participants Subjects in Cohort 2 received a single oral dose of 225 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 225 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.
Time to Maximum Plasma Concentration (Tmax) of IV Paclitaxel When Given in Combination With Oral AZD1775 and IV Carboplatin	2.99 hours Interval 1.55 to 3.08	—	3.03 hours Interval 3.02 to 3.1

SECONDARY outcome

Timeframe: AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion

Population: The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained.

Outcome measures

Measure	Cohort 1 n=6 Participants Subjects in Cohort 1 received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 1a Subjects in Cohort 1a received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 2 n=4 Participants Subjects in Cohort 2 received a single oral dose of 225 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 225 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.
Time to Last Detectable Concentration (Tlast) of Paclitaxel When Given in Combination With Oral AZD1775 and IV Carboplatin	2.99 hours Interval 1.55 to 3.08	—	3.03 hours Interval 3.02 to 3.1

SECONDARY outcome

Timeframe: AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion

Population: The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained.

Outcome measures

Measure	Cohort 1 n=3 Participants Subjects in Cohort 1 received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 1a n=4 Participants Subjects in Cohort 1a received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 2 n=3 Participants Subjects in Cohort 2 received a single oral dose of 225 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 225 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.
Peak Plasma Concentration (Cmax) of Platinum Following Single IV Infusion of Carboplatin Over 1 Hour in Combination With Single Oral Dose AZD1775 Alone (Cohort 1a) or With IV Paclitaxel (Cohorts 1 and 2)	13300 ng/mL Geometric Coefficient of Variation 17.41	18550 ng/mL Geometric Coefficient of Variation 19.87	17500 ng/mL Geometric Coefficient of Variation 34.93

SECONDARY outcome

Timeframe: AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion

Population: The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained.

Outcome measures

Measure	Cohort 1 n=3 Participants Subjects in Cohort 1 received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 1a n=4 Participants Subjects in Cohort 1a received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 2 n=3 Participants Subjects in Cohort 2 received a single oral dose of 225 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 225 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.
Area Under Plasma Concentration-time Curve From 0 to Last Measurable Conc. (AUC0-t) of Platinum Following Single IV Infusion of Carboplatin Over 1 Hour in Combination With Single Oral Dose AZD1775 Alone (Cohort 1a) or With IV Paclitaxel (Cohorts 1 & 2)	39370 h*ng/mL Geometric Coefficient of Variation 7.027	44630 h*ng/mL Geometric Coefficient of Variation 2.552	51340 h*ng/mL Geometric Coefficient of Variation 12.24

SECONDARY outcome

Timeframe: AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion

Population: The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained.

Outcome measures

Measure	Cohort 1 n=3 Participants Subjects in Cohort 1 received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 1a n=4 Participants Subjects in Cohort 1a received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 2 n=3 Participants Subjects in Cohort 2 received a single oral dose of 225 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 225 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.
Plasma Concentration of Platinum at the End of Infusion (Ceoi) When Given as a 1 Hour Infusion in Combination With Oral AZD1775 and IV Paclitaxel.	13300 ng/mL Geometric Coefficient of Variation 17.41	18550 ng/mL Geometric Coefficient of Variation 19.87	17500 ng/mL Geometric Coefficient of Variation 34.93

SECONDARY outcome

Timeframe: AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion

Population: The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained.

Outcome measures

Measure	Cohort 1 n=3 Participants Subjects in Cohort 1 received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 1a n=4 Participants Subjects in Cohort 1a received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 2 n=3 Participants Subjects in Cohort 2 received a single oral dose of 225 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 225 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.
Time to Peak Plasma Concentration of Platinum (Tmax) When Given as a 1 Hour Infusion in Combination With Oral AZD1775 and IV Paclitaxel.	1.02 hours Interval 1.02 to 1.1	1.02 hours Interval 1.0 to 1.03	1.02 hours Interval 1.0 to 1.02

SECONDARY outcome

Timeframe: AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion

Population: The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained.

Outcome measures

Measure	Cohort 1 n=3 Participants Subjects in Cohort 1 received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 1a n=4 Participants Subjects in Cohort 1a received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 2 n=3 Participants Subjects in Cohort 2 received a single oral dose of 225 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 225 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.
Time to Last Detectable Concentration of Platinum (Tlast) When Given as a 1 Hour Infusion in Combination With Oral AZD1775 and IV Paclitaxel.	7.98 hours Interval 7.83 to 8.0	7.28 hours Interval 7.2 to 7.98	8.00 hours Interval 7.83 to 8.08

SECONDARY outcome

Timeframe: AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion

Population: The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained.

Outcome measures

Measure	Cohort 1 n=3 Participants Subjects in Cohort 1 received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 1a n=1 Participants Subjects in Cohort 1a received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 2 Subjects in Cohort 2 received a single oral dose of 225 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 225 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.
Peak Plasma Concentration (Cmax) of Platinum Following Single IV Infusion of Carboplatin Over 2 Hours in Combination With Single Oral Dose AZD1775 Alone (Cohort 1a) or With IV Paclitaxel (Cohorts 1 and 2)	15960 ng/mL Geometric Coefficient of Variation 26.51	13200 ng/mL Geometric Coefficient of Variation 0	—

SECONDARY outcome

Timeframe: AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion

Population: The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained.

Outcome measures

Measure	Cohort 1 n=6 Participants Subjects in Cohort 1 received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 1a n=1 Participants Subjects in Cohort 1a received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 2 Subjects in Cohort 2 received a single oral dose of 225 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 225 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.
Area Under Plasma Concentration-time Curve From 0 to Last Measurable Conc. (AUC0-t) of Platinum Following Single IV Infusion of Carboplatin Over 2 Hours in Combination With Single Oral Dose AZD1775 Alone (Cohort 1a) or With IV Paclitaxel (Cohorts 1 & 2)	56240 h*ng/mL Geometric Coefficient of Variation 17.2	48700 h*ng/mL Geometric Coefficient of Variation 0	—

SECONDARY outcome

Timeframe: AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion

Population: The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained.

Outcome measures

Measure	Cohort 1 n=3 Participants Subjects in Cohort 1 received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 1a n=1 Participants Subjects in Cohort 1a received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 2 Subjects in Cohort 2 received a single oral dose of 225 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 225 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.
Plasma Concentration of Platinum at the End of Infusion (Ceoi) When Given as a 2 Hour Infusion in Combination With Oral AZD1775 and IV Paclitaxel.	15960 ng/mL Geometric Coefficient of Variation 26.51	12200 ng/mL Geometric Coefficient of Variation 0	—

SECONDARY outcome

Timeframe: AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion

Population: The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained.

Outcome measures

Measure	Cohort 1 n=3 Participants Subjects in Cohort 1 received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 1a n=1 Participants Subjects in Cohort 1a received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 2 Subjects in Cohort 2 received a single oral dose of 225 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 225 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.
Time to Peak Plasma Concentration of Platinum (Tmax) When Given as a 2 Hour Infusion in Combination With Oral AZD1775 and IV Paclitaxel.	1.97 hours Interval 1.92 to 2.0	1.08 hours Interval 1.08 to 1.08	—

SECONDARY outcome

Timeframe: AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion

Population: The pharmacokinetic analysis set consisted of all dosed patients for whom an adequate PK profile was obtained.

Outcome measures

Measure	Cohort 1 n=3 Participants Subjects in Cohort 1 received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 1a n=1 Participants Subjects in Cohort 1a received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 2 Subjects in Cohort 2 received a single oral dose of 225 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 225 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.
Time to Last Detectable Concentration of Platinum (Tlast) When Given as a 2 Hour Infusion in Combination With Oral AZD1775 and IV Paclitaxel.	7.95 hours Interval 7.92 to 8.03	8.00 hours Interval 8.0 to 8.0	—

Adverse Events

Cohort 1

Serious events: 3 serious events

Other events: 7 other events

Deaths: 1 deaths

Cohort 1a

Serious events: 0 serious events

Other events: 6 other events

Deaths: 1 deaths

Cohort 2

Serious events: 4 serious events

Other events: 6 other events

Deaths: 1 deaths

Serious adverse events

Measure	Cohort 1 n=7 participants at risk Subjects in Cohort 1 received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 1a n=6 participants at risk Subjects in Cohort 1a received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 2 n=6 participants at risk Subjects in Cohort 2 received a single oral dose of 225 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 225 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.
Blood and lymphatic system disorders Febrile neutropenia	14.3% 1/7 • Number of events 1 • Up to 18 months.	0.00% 0/6 • Up to 18 months.	16.7% 1/6 • Number of events 1 • Up to 18 months.
Blood and lymphatic system disorders Neutropenia	0.00% 0/7 • Up to 18 months.	0.00% 0/6 • Up to 18 months.	33.3% 2/6 • Number of events 3 • Up to 18 months.
Gastrointestinal disorders Diarrhoea	0.00% 0/7 • Up to 18 months.	0.00% 0/6 • Up to 18 months.	16.7% 1/6 • Number of events 1 • Up to 18 months.
Gastrointestinal disorders Nausea	14.3% 1/7 • Number of events 1 • Up to 18 months.	0.00% 0/6 • Up to 18 months.	0.00% 0/6 • Up to 18 months.
Gastrointestinal disorders Vomiting	14.3% 1/7 • Number of events 1 • Up to 18 months.	0.00% 0/6 • Up to 18 months.	0.00% 0/6 • Up to 18 months.
Infections and infestations Sepsis	0.00% 0/7 • Up to 18 months.	0.00% 0/6 • Up to 18 months.	33.3% 2/6 • Number of events 2 • Up to 18 months.
Infections and infestations Clostridium difficile colitis	0.00% 0/7 • Up to 18 months.	0.00% 0/6 • Up to 18 months.	16.7% 1/6 • Number of events 1 • Up to 18 months.
General disorders Pyrexia	14.3% 1/7 • Number of events 1 • Up to 18 months.	0.00% 0/6 • Up to 18 months.	0.00% 0/6 • Up to 18 months.
Hepatobiliary disorders Hepatic function abnormal	14.3% 1/7 • Number of events 1 • Up to 18 months.	0.00% 0/6 • Up to 18 months.	0.00% 0/6 • Up to 18 months.
Investigations Platelet count decreased	14.3% 1/7 • Number of events 2 • Up to 18 months.	0.00% 0/6 • Up to 18 months.	0.00% 0/6 • Up to 18 months.
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	0.00% 0/7 • Up to 18 months.	0.00% 0/6 • Up to 18 months.	16.7% 1/6 • Number of events 1 • Up to 18 months.
Vascular disorders Hypotension	14.3% 1/7 • Number of events 1 • Up to 18 months.	0.00% 0/6 • Up to 18 months.	0.00% 0/6 • Up to 18 months.

Other adverse events

Measure	Cohort 1 n=7 participants at risk Subjects in Cohort 1 received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 1a n=6 participants at risk Subjects in Cohort 1a received a single oral dose of 175 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 175 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.	Cohort 2 n=6 participants at risk Subjects in Cohort 2 received a single oral dose of 225 mg of AZD1775 monotherapy followed 5 ± 2 days later by combination therapy consisting of 5 oral doses of 225 mg AZD1775 given 12 hours apart on days 1, 2, and 3 and single doses of intravenous paclitaxel (175 mg/m²) and intravenous carboplatin (AUC 5) given on day 1 of 21 day cycles.
Metabolism and nutrition disorders Dehydration	14.3% 1/7 • Number of events 1 • Up to 18 months.	0.00% 0/6 • Up to 18 months.	16.7% 1/6 • Number of events 1 • Up to 18 months.
Metabolism and nutrition disorders Hypocalcaemia	14.3% 1/7 • Number of events 4 • Up to 18 months.	16.7% 1/6 • Number of events 1 • Up to 18 months.	16.7% 1/6 • Number of events 4 • Up to 18 months.
Metabolism and nutrition disorders Hypokalemia	14.3% 1/7 • Number of events 1 • Up to 18 months.	33.3% 2/6 • Number of events 2 • Up to 18 months.	33.3% 2/6 • Number of events 5 • Up to 18 months.
Metabolism and nutrition disorders Hyponatremia	14.3% 1/7 • Number of events 2 • Up to 18 months.	0.00% 0/6 • Up to 18 months.	16.7% 1/6 • Number of events 1 • Up to 18 months.
Metabolism and nutrition disorders Hypophosphatemia	14.3% 1/7 • Number of events 3 • Up to 18 months.	16.7% 1/6 • Number of events 1 • Up to 18 months.	33.3% 2/6 • Number of events 6 • Up to 18 months.
Metabolism and nutrition disorders Hypercalcemia	0.00% 0/7 • Up to 18 months.	0.00% 0/6 • Up to 18 months.	16.7% 1/6 • Number of events 6 • Up to 18 months.
Musculoskeletal and connective tissue disorders Back pain	28.6% 2/7 • Number of events 2 • Up to 18 months.	16.7% 1/6 • Number of events 1 • Up to 18 months.	0.00% 0/6 • Up to 18 months.
Musculoskeletal and connective tissue disorders Myalgia	28.6% 2/7 • Number of events 2 • Up to 18 months.	0.00% 0/6 • Up to 18 months.	33.3% 2/6 • Number of events 3 • Up to 18 months.
Musculoskeletal and connective tissue disorders Pain in extremity	14.3% 1/7 • Number of events 1 • Up to 18 months.	0.00% 0/6 • Up to 18 months.	0.00% 0/6 • Up to 18 months.
Musculoskeletal and connective tissue disorders Arthralgia	28.6% 2/7 • Number of events 2 • Up to 18 months.	0.00% 0/6 • Up to 18 months.	0.00% 0/6 • Up to 18 months.
Musculoskeletal and connective tissue disorders Muscle spasms	14.3% 1/7 • Number of events 1 • Up to 18 months.	0.00% 0/6 • Up to 18 months.	0.00% 0/6 • Up to 18 months.
Musculoskeletal and connective tissue disorders Flank pain	0.00% 0/7 • Up to 18 months.	16.7% 1/6 • Number of events 1 • Up to 18 months.	0.00% 0/6 • Up to 18 months.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/7 • Up to 18 months.	0.00% 0/6 • Up to 18 months.	16.7% 1/6 • Number of events 3 • Up to 18 months.
Metabolism and nutrition disorders Hypercholesterolemia	0.00% 0/7 • Up to 18 months.	0.00% 0/6 • Up to 18 months.	16.7% 1/6 • Number of events 1 • Up to 18 months.
Injury, poisoning and procedural complications Postoperative pain	0.00% 0/7 • Up to 18 months.	0.00% 0/6 • Up to 18 months.	16.7% 1/6 • Number of events 2 • Up to 18 months.
Investigations Blood lactate dehydrogenase increased	14.3% 1/7 • Number of events 2 • Up to 18 months.	0.00% 0/6 • Up to 18 months.	0.00% 0/6 • Up to 18 months.
Investigations C-reactive protein increased	14.3% 1/7 • Number of events 3 • Up to 18 months.	0.00% 0/6 • Up to 18 months.	0.00% 0/6 • Up to 18 months.
Investigations Hematocrit decreased	14.3% 1/7 • Number of events 3 • Up to 18 months.	0.00% 0/6 • Up to 18 months.	0.00% 0/6 • Up to 18 months.
Investigations Monocyte count decreased	14.3% 1/7 • Number of events 1 • Up to 18 months.	0.00% 0/6 • Up to 18 months.	0.00% 0/6 • Up to 18 months.
Investigations Platelet count decreased	57.1% 4/7 • Number of events 50 • Up to 18 months.	50.0% 3/6 • Number of events 29 • Up to 18 months.	50.0% 3/6 • Number of events 21 • Up to 18 months.
Investigations White blood cell count decreased	71.4% 5/7 • Number of events 26 • Up to 18 months.	50.0% 3/6 • Number of events 10 • Up to 18 months.	83.3% 5/6 • Number of events 31 • Up to 18 months.
Investigations Blood alklaine phosphatase increased	14.3% 1/7 • Number of events 1 • Up to 18 months.	0.00% 0/6 • Up to 18 months.	0.00% 0/6 • Up to 18 months.
Investigations Neutrophil count decreased	42.9% 3/7 • Number of events 10 • Up to 18 months.	66.7% 4/6 • Number of events 8 • Up to 18 months.	50.0% 3/6 • Number of events 15 • Up to 18 months.
Investigations Aspartate aminotransferase increased	0.00% 0/7 • Up to 18 months.	33.3% 2/6 • Number of events 6 • Up to 18 months.	16.7% 1/6 • Number of events 1 • Up to 18 months.
Investigations Alanine aminotransferase increased	0.00% 0/7 • Up to 18 months.	16.7% 1/6 • Number of events 4 • Up to 18 months.	0.00% 0/6 • Up to 18 months.
Metabolism and nutrition disorders Decreased appetite	57.1% 4/7 • Number of events 5 • Up to 18 months.	66.7% 4/6 • Number of events 10 • Up to 18 months.	50.0% 3/6 • Number of events 4 • Up to 18 months.
Metabolism and nutrition disorders Hyperglycaemia	42.9% 3/7 • Number of events 12 • Up to 18 months.	0.00% 0/6 • Up to 18 months.	0.00% 0/6 • Up to 18 months.
Metabolism and nutrition disorders Hypoalbuminemia	28.6% 2/7 • Number of events 2 • Up to 18 months.	0.00% 0/6 • Up to 18 months.	33.3% 2/6 • Number of events 5 • Up to 18 months.
Metabolism and nutrition disorders Hypomagnesaemia	14.3% 1/7 • Number of events 1 • Up to 18 months.	0.00% 0/6 • Up to 18 months.	16.7% 1/6 • Number of events 2 • Up to 18 months.
Blood and lymphatic system disorders Anaemia	85.7% 6/7 • Number of events 48 • Up to 18 months.	66.7% 4/6 • Number of events 21 • Up to 18 months.	83.3% 5/6 • Number of events 37 • Up to 18 months.
Blood and lymphatic system disorders Neutropenia	42.9% 3/7 • Number of events 18 • Up to 18 months.	0.00% 0/6 • Up to 18 months.	33.3% 2/6 • Number of events 9 • Up to 18 months.
Blood and lymphatic system disorders Thrombocytopenia	14.3% 1/7 • Number of events 9 • Up to 18 months.	16.7% 1/6 • Number of events 6 • Up to 18 months.	33.3% 2/6 • Number of events 23 • Up to 18 months.
Blood and lymphatic system disorders Febrile Neutropenia	0.00% 0/7 • Up to 18 months.	0.00% 0/6 • Up to 18 months.	33.3% 2/6 • Number of events 2 • Up to 18 months.
Eye disorders Eyelid Oedema	0.00% 0/7 • Up to 18 months.	0.00% 0/6 • Up to 18 months.	16.7% 1/6 • Number of events 1 • Up to 18 months.
Gastrointestinal disorders Nausea	85.7% 6/7 • Number of events 36 • Up to 18 months.	100.0% 6/6 • Number of events 27 • Up to 18 months.	83.3% 5/6 • Number of events 37 • Up to 18 months.
Gastrointestinal disorders Abdominal pain upper	14.3% 1/7 • Number of events 1 • Up to 18 months.	16.7% 1/6 • Number of events 2 • Up to 18 months.	0.00% 0/6 • Up to 18 months.
Gastrointestinal disorders Constipation	28.6% 2/7 • Number of events 4 • Up to 18 months.	0.00% 0/6 • Up to 18 months.	50.0% 3/6 • Number of events 5 • Up to 18 months.
Gastrointestinal disorders Diarrhoea	71.4% 5/7 • Number of events 25 • Up to 18 months.	50.0% 3/6 • Number of events 13 • Up to 18 months.	66.7% 4/6 • Number of events 49 • Up to 18 months.
Gastrointestinal disorders Abdominal distension	14.3% 1/7 • Number of events 1 • Up to 18 months.	16.7% 1/6 • Number of events 1 • Up to 18 months.	16.7% 1/6 • Number of events 1 • Up to 18 months.
Gastrointestinal disorders Abdominal pain	28.6% 2/7 • Number of events 4 • Up to 18 months.	33.3% 2/6 • Number of events 4 • Up to 18 months.	33.3% 2/6 • Number of events 7 • Up to 18 months.
Gastrointestinal disorders Dyspepsia	14.3% 1/7 • Number of events 1 • Up to 18 months.	0.00% 0/6 • Up to 18 months.	0.00% 0/6 • Up to 18 months.
Gastrointestinal disorders Vomiting	71.4% 5/7 • Number of events 20 • Up to 18 months.	66.7% 4/6 • Number of events 15 • Up to 18 months.	83.3% 5/6 • Number of events 27 • Up to 18 months.
Gastrointestinal disorders Oesphageal disorder	14.3% 1/7 • Number of events 1 • Up to 18 months.	0.00% 0/6 • Up to 18 months.	0.00% 0/6 • Up to 18 months.
Gastrointestinal disorders Ileus	14.3% 1/7 • Number of events 1 • Up to 18 months.	0.00% 0/6 • Up to 18 months.	0.00% 0/6 • Up to 18 months.
Gastrointestinal disorders Dysphagia	14.3% 1/7 • Number of events 1 • Up to 18 months.	0.00% 0/6 • Up to 18 months.	0.00% 0/6 • Up to 18 months.
Gastrointestinal disorders Proctologia	14.3% 1/7 • Number of events 1 • Up to 18 months.	16.7% 1/6 • Number of events 1 • Up to 18 months.	50.0% 3/6 • Number of events 7 • Up to 18 months.
Gastrointestinal disorders Intestinal obstruction	0.00% 0/7 • Up to 18 months.	16.7% 1/6 • Number of events 1 • Up to 18 months.	0.00% 0/6 • Up to 18 months.
Gastrointestinal disorders Gingival pain	0.00% 0/7 • Up to 18 months.	16.7% 1/6 • Number of events 1 • Up to 18 months.	0.00% 0/6 • Up to 18 months.
Gastrointestinal disorders Anal Haemorrhage	0.00% 0/7 • Up to 18 months.	0.00% 0/6 • Up to 18 months.	16.7% 1/6 • Number of events 1 • Up to 18 months.
General disorders Oedema	28.6% 2/7 • Number of events 2 • Up to 18 months.	16.7% 1/6 • Number of events 1 • Up to 18 months.	0.00% 0/6 • Up to 18 months.
General disorders Fatugue	28.6% 2/7 • Number of events 3 • Up to 18 months.	33.3% 2/6 • Number of events 5 • Up to 18 months.	16.7% 1/6 • Number of events 1 • Up to 18 months.
General disorders Gait disturbance	14.3% 1/7 • Number of events 1 • Up to 18 months.	0.00% 0/6 • Up to 18 months.	0.00% 0/6 • Up to 18 months.
General disorders Pyrexia	42.9% 3/7 • Number of events 11 • Up to 18 months.	33.3% 2/6 • Number of events 4 • Up to 18 months.	66.7% 4/6 • Number of events 9 • Up to 18 months.
General disorders Asthenia	14.3% 1/7 • Number of events 2 • Up to 18 months.	16.7% 1/6 • Number of events 1 • Up to 18 months.	33.3% 2/6 • Number of events 4 • Up to 18 months.
General disorders Chills	14.3% 1/7 • Number of events 1 • Up to 18 months.	16.7% 1/6 • Number of events 1 • Up to 18 months.	0.00% 0/6 • Up to 18 months.
General disorders Chest pain	0.00% 0/7 • Up to 18 months.	16.7% 1/6 • Number of events 1 • Up to 18 months.	0.00% 0/6 • Up to 18 months.
General disorders Malaise	0.00% 0/7 • Up to 18 months.	16.7% 1/6 • Number of events 7 • Up to 18 months.	0.00% 0/6 • Up to 18 months.
Immune system disorders Hypersensitivity	0.00% 0/7 • Up to 18 months.	0.00% 0/6 • Up to 18 months.	16.7% 1/6 • Number of events 1 • Up to 18 months.
Infections and infestations Herpes zoster	14.3% 1/7 • Number of events 1 • Up to 18 months.	0.00% 0/6 • Up to 18 months.	0.00% 0/6 • Up to 18 months.
Infections and infestations Liver abscess	14.3% 1/7 • Number of events 1 • Up to 18 months.	0.00% 0/6 • Up to 18 months.	0.00% 0/6 • Up to 18 months.
Infections and infestations Cystitis	14.3% 1/7 • Number of events 2 • Up to 18 months.	0.00% 0/6 • Up to 18 months.	0.00% 0/6 • Up to 18 months.
Infections and infestations Bone abscess	0.00% 0/7 • Up to 18 months.	0.00% 0/6 • Up to 18 months.	16.7% 1/6 • Number of events 2 • Up to 18 months.
Infections and infestations Urinary tract infection	0.00% 0/7 • Up to 18 months.	0.00% 0/6 • Up to 18 months.	16.7% 1/6 • Number of events 1 • Up to 18 months.
Infections and infestations Anal infection	0.00% 0/7 • Up to 18 months.	0.00% 0/6 • Up to 18 months.	16.7% 1/6 • Number of events 1 • Up to 18 months.
Infections and infestations Herpes simplex	0.00% 0/7 • Up to 18 months.	0.00% 0/6 • Up to 18 months.	16.7% 1/6 • Number of events 1 • Up to 18 months.
Infections and infestations Fallopian tube abscess	0.00% 0/7 • Up to 18 months.	0.00% 0/6 • Up to 18 months.	16.7% 1/6 • Number of events 1 • Up to 18 months.
Injury, poisoning and procedural complications Postoperative wound complication	14.3% 1/7 • Number of events 1 • Up to 18 months.	0.00% 0/6 • Up to 18 months.	0.00% 0/6 • Up to 18 months.
Injury, poisoning and procedural complications Radiation skin injury	14.3% 1/7 • Number of events 1 • Up to 18 months.	0.00% 0/6 • Up to 18 months.	0.00% 0/6 • Up to 18 months.
Injury, poisoning and procedural complications Rash	14.3% 1/7 • Number of events 1 • Up to 18 months.	0.00% 0/6 • Up to 18 months.	0.00% 0/6 • Up to 18 months.
Musculoskeletal and connective tissue disorders Low back pain	0.00% 0/7 • Up to 18 months.	0.00% 0/6 • Up to 18 months.	16.7% 1/6 • Number of events 1 • Up to 18 months.
Nervous system disorders Lethargy	14.3% 1/7 • Number of events 1 • Up to 18 months.	0.00% 0/6 • Up to 18 months.	0.00% 0/6 • Up to 18 months.
Nervous system disorders Neuralgia	14.3% 1/7 • Number of events 1 • Up to 18 months.	0.00% 0/6 • Up to 18 months.	0.00% 0/6 • Up to 18 months.
Nervous system disorders Peripheral sensory neuropathy	28.6% 2/7 • Number of events 4 • Up to 18 months.	33.3% 2/6 • Number of events 2 • Up to 18 months.	16.7% 1/6 • Number of events 2 • Up to 18 months.
Nervous system disorders Peripheral neuropathy	14.3% 1/7 • Number of events 3 • Up to 18 months.	0.00% 0/6 • Up to 18 months.	16.7% 1/6 • Number of events 1 • Up to 18 months.
Nervous system disorders Headache	14.3% 1/7 • Number of events 1 • Up to 18 months.	16.7% 1/6 • Number of events 1 • Up to 18 months.	33.3% 2/6 • Number of events 2 • Up to 18 months.
Nervous system disorders Dizziness	0.00% 0/7 • Up to 18 months.	16.7% 1/6 • Number of events 1 • Up to 18 months.	16.7% 1/6 • Number of events 1 • Up to 18 months.
Nervous system disorders Akathisia	0.00% 0/7 • Up to 18 months.	0.00% 0/6 • Up to 18 months.	16.7% 1/6 • Number of events 1 • Up to 18 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain	14.3% 1/7 • Number of events 1 • Up to 18 months.	0.00% 0/6 • Up to 18 months.	0.00% 0/6 • Up to 18 months.
Psychiatric disorders Anxiety	14.3% 1/7 • Number of events 2 • Up to 18 months.	16.7% 1/6 • Number of events 2 • Up to 18 months.	0.00% 0/6 • Up to 18 months.
Psychiatric disorders Insomnia	14.3% 1/7 • Number of events 2 • Up to 18 months.	33.3% 2/6 • Number of events 2 • Up to 18 months.	33.3% 2/6 • Number of events 5 • Up to 18 months.
Renal and urinary disorders Azotemia	14.3% 1/7 • Number of events 1 • Up to 18 months.	0.00% 0/6 • Up to 18 months.	0.00% 0/6 • Up to 18 months.
Renal and urinary disorders Micturition urgency	14.3% 1/7 • Number of events 2 • Up to 18 months.	0.00% 0/6 • Up to 18 months.	0.00% 0/6 • Up to 18 months.
Renal and urinary disorders Chromaturia	0.00% 0/7 • Up to 18 months.	0.00% 0/6 • Up to 18 months.	16.7% 1/6 • Number of events 1 • Up to 18 months.
Reproductive system and breast disorders Vaginal haemorrhage	0.00% 0/7 • Up to 18 months.	0.00% 0/6 • Up to 18 months.	16.7% 1/6 • Number of events 1 • Up to 18 months.
Respiratory, thoracic and mediastinal disorders Pleural effusion	28.6% 2/7 • Number of events 3 • Up to 18 months.	16.7% 1/6 • Number of events 1 • Up to 18 months.	33.3% 2/6 • Number of events 3 • Up to 18 months.
Respiratory, thoracic and mediastinal disorders Oropharyngeal discomfort	14.3% 1/7 • Number of events 1 • Up to 18 months.	0.00% 0/6 • Up to 18 months.	16.7% 1/6 • Number of events 1 • Up to 18 months.
Respiratory, thoracic and mediastinal disorders Productive cough	0.00% 0/7 • Up to 18 months.	33.3% 2/6 • Number of events 2 • Up to 18 months.	0.00% 0/6 • Up to 18 months.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/7 • Up to 18 months.	33.3% 2/6 • Number of events 2 • Up to 18 months.	16.7% 1/6 • Number of events 2 • Up to 18 months.
Respiratory, thoracic and mediastinal disorders Sputum increased	0.00% 0/7 • Up to 18 months.	0.00% 0/6 • Up to 18 months.	16.7% 1/6 • Number of events 1 • Up to 18 months.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/7 • Up to 18 months.	0.00% 0/6 • Up to 18 months.	16.7% 1/6 • Number of events 1 • Up to 18 months.
Skin and subcutaneous tissue disorders Alopecia	28.6% 2/7 • Number of events 3 • Up to 18 months.	0.00% 0/6 • Up to 18 months.	16.7% 1/6 • Number of events 1 • Up to 18 months.
Skin and subcutaneous tissue disorders Pruritus	14.3% 1/7 • Number of events 1 • Up to 18 months.	0.00% 0/6 • Up to 18 months.	16.7% 1/6 • Number of events 1 • Up to 18 months.
Skin and subcutaneous tissue disorders Ingrown nail	14.3% 1/7 • Number of events 1 • Up to 18 months.	0.00% 0/6 • Up to 18 months.	16.7% 1/6 • Number of events 1 • Up to 18 months.
Skin and subcutaneous tissue disorders Vascular skin disorder	14.3% 1/7 • Number of events 1 • Up to 18 months.	0.00% 0/6 • Up to 18 months.	0.00% 0/6 • Up to 18 months.
Skin and subcutaneous tissue disorders Dry skin	14.3% 1/7 • Number of events 1 • Up to 18 months.	0.00% 0/6 • Up to 18 months.	0.00% 0/6 • Up to 18 months.
Skin and subcutaneous tissue disorders Pruritus generalised	0.00% 0/7 • Up to 18 months.	16.7% 1/6 • Number of events 1 • Up to 18 months.	0.00% 0/6 • Up to 18 months.
Skin and subcutaneous tissue disorders Hyperhydrosis	0.00% 0/7 • Up to 18 months.	16.7% 1/6 • Number of events 1 • Up to 18 months.	0.00% 0/6 • Up to 18 months.
Surgical and medical procedures Oophorectomy	0.00% 0/7 • Up to 18 months.	0.00% 0/6 • Up to 18 months.	16.7% 1/6 • Number of events 1 • Up to 18 months.
Vascular disorders Hypotension	28.6% 2/7 • Number of events 2 • Up to 18 months.	0.00% 0/6 • Up to 18 months.	16.7% 1/6 • Number of events 3 • Up to 18 months.
Vascular disorders Arteriosclerosis	14.3% 1/7 • Number of events 1 • Up to 18 months.	0.00% 0/6 • Up to 18 months.	0.00% 0/6 • Up to 18 months.

Additional Information

Lone Ottesen

AstraZeneca

Phone: 1-877-240-9479

Email: ClinicalTrialTransparency@astrazeneca.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place