Advanced Solid Tumours
Conditions
Brief summary
This is a phase Ib, open-label, multicentre study of AZD1775 administered orally in monotherapy and in combination with carboplatin and paclitaxel to Asian patients with advanced solid tumours.
Detailed description
This is a phase Ib, open label, multicentre study of AZD1775 administered orally in monotherapy and in combination with carboplatin and paclitaxel in Asian patients with advanced solid tumours. The study design allows escalation or de-escalation of AZD1775 in combination with carboplatin and paclitaxel with intensive safety monitoring to ensure the safety of the patients. Approximately 12 evaluable patients will be enrolled in the dose-finding portion of this study. The total number of patients will depend upon the number of combination dose level evaluations necessary to define the recommended dose for further clinical evaluation. The proposed combination doses are : Dose level-1; Dose level 1; Dose level 2 (if Dose Level 1 tolerated). All combination doses other than Combination Dose level 1 may be subject to change by the SRC in light of emerging data. At least 3 and up to 6 evaluable patients will be required for each dose finding cohort. Once the recommended dose for further clinical evaluation is established, additional 3 to 6 patients may be enrolled to the cohort where the recommended dose has been defined to further characterise the safety, tolerability, pharmacokinetics, and efficacy profiles of AZD1775 in combination with paclitaxel and carboplatin. If this dose is subsequently found to be non-tolerated, alternative doses and/or schedules may be explored. This will be determined by the SRC.
Interventions
DRUGAZD1775
AZD1775 is a highly selective, adenosine-triphosphate (ATP) competitive, small-molecule inhibitor of the WEE1 kinase that sensitizes tumour cells to cytotoxic agents and is being developed for the treatment of advanced solid tumours and p53 pathway deficient malignancies. Gemcitabine is a nucleoside analog used as chemotherapy.
DRUGPaclitaxel
Paclitaxel is a mitotic inhibitor used in cancer chemotherapy ; it and docetaxel represent the taxane family of drugs.
DRUGcarboplatin
Carboplatin is a chemotherapy drug used against some forms of cancer (mainly ovarian carcinoma, lung, head and neck cancers as well as endometrial, esophageal, bladder, breast and cervical; central nervous system or germ cell tumors; osteogenic sarcoma, and as preparation for a stem cell or bone marrow transplant.).
Sponsors
AstraZeneca
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
* Histological or cytological confirmation of a locally advanced or metastatic solid tumour, excluding lymphoma, that failed to respond to standard therapy, progressed despite standard therapy, or for which standard therapy does not exist. * At least 1 measureable lesion that can be accurately assessed at baseline by computerised tomography (CT) or magnetic resonance imaging (MRI) for solid tumours assessed using RECIST v1.1. * World Health Organisation performance status 0 to 1 with no deterioration over the previous 2 weeks and a minimum life expectancy of ≥12 weeks.
Exclusion criteria
* Any cytotoxic chemotherapy, investigational agents or other anticancer drugs from a previous treatment regimen or clinical study within 14 days (if investigational agent does not have well characterised PK profile) or 5 × half-lives of the first dose of study treatment * Patient has had prescription or non-prescription drugs or other products (ie, grapefruit juice) known to be sensitive to CYP3A4 substrates or CYP3A4 substrates with a narrow therapeutic index, or to be moderate to strong inhibitors or inducers of CYP3A4, which cannot be discontinued 2 weeks before Day 1 of dosing and withheld throughout the study until 2 weeks after the last dose of study drug. Co-administration of aprepitant during this study is prohibited. * AZD1775 is an inhibitor of breast cancer resistance protein (BCRP). The use of statins including Atorvastatin which are substrates for BCRP are therefore prohibited and patients should be moved on to non-BCRP alternatives.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Treatment-Emergent Adverse Events | Up to 21 days (1 Cycle) | 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. |
| Number of Treatment-Emergent Adverse Events (TEAE) | Up to 21 days (1 Cycle) | 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. |
| Number of Patients With Treatment-Emergent Adverse Events During AZD1775 Monotherapy Cycle by System Organ Class and Preferred Term | Up to 1 week | 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. |
| Number of Patients With Clinically Important Changes in Haematology and Coagulation TEAEs by System Organ Class and Preferred Term | Up to 21 days (1 Cycle) | 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. |
| Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term | Up to 21 days (1 Cycle) | 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. |
| Number of Patients With Clinically Important Abnormalities in Vital Signs by Preferred Term | Up to 21 days (1 Cycle) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Peak Plasma Concentration (Cmax) of AZD1775 Following Single Dose Administration of AZD1775 Monotherapy | 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 | — |
| Time to Maximum Plasma Concentration (Tmax) of AZD1775 Following Single Dose Administration of AZD1775 Monotherapy | 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 | — |
| 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 | 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 | — |
| Plasma Concentration of AZD1775 8 Hours After Single Dose Administration (C8h) of AZD1775 Monotherapy | 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 | — |
| 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) | 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 | — |
| 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) | 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 | — |
| 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) | 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 | — |
| 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) | 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 | — |
| 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) | 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 | — |
| 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) | 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 | — |
| 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) | 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 | — |
| 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) | 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 | — |
| Peak Plasma Concentration (Cmax) of Paclitaxel Following Single IV Infusion in Combination With Single Dose Oral AZD1775 and IV Carboplatin | 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 | — |
| Best Overall Response | Up to 18 months | 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. |
| Plasma Concentration of Paclitaxel at the End of Infusion (Ceoi) When Given Combination With Oral AZD1775 and IV Carboplatin. | 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 | — |
| Time to Maximum Plasma Concentration (Tmax) of IV Paclitaxel When Given in Combination With Oral AZD1775 and IV Carboplatin | 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 | — |
| Time to Last Detectable Concentration (Tlast) of Paclitaxel When Given in Combination With Oral AZD1775 and IV Carboplatin | 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 | — |
| 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) | 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 | — |
| 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) | 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 | — |
| 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. | 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 | — |
| Time to Peak Plasma Concentration of Platinum (Tmax) When Given as a 1 Hour Infusion in Combination With Oral AZD1775 and IV Paclitaxel. | 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 | — |
| Time to Last Detectable Concentration of Platinum (Tlast) When Given as a 1 Hour Infusion in Combination With Oral AZD1775 and IV Paclitaxel. | 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 | — |
| 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) | 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 | — |
| 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) | 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 | — |
| 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. | 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 | — |
| Time to Peak Plasma Concentration of Platinum (Tmax) When Given as a 2 Hour Infusion in Combination With Oral AZD1775 and IV Paclitaxel. | 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 | — |
| Time to Last Detectable Concentration of Platinum (Tlast) When Given as a 2 Hour Infusion in Combination With Oral AZD1775 and IV Paclitaxel. | 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 | — |
| 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 | 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 | — |
| Number of Patients With an Objective Response | Up to 18 months | Objective response is defined as either a complete response or a partial response. |
| Percentage of Patients With an Objective Response | Up to 18 months | Objective response is defined as either a complete response or a partial response. |
| Number of Patients With Clinical Benefit | Up to 18 months | Clinical benefit is defined as achieving complete response, partial response, or stable disease. |
| Percentage of Patients With Clinical Benefit | Up to 18 months | Clinical benefit is defined as achieving complete response, partial response, or stable disease. |
| Duration of Response | 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. |
Countries
Australia, Japan, South Korea
Participant flow
Recruitment details
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.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 7 |
| 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. | 6 |
| 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. | 6 |
| Total | 19 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 1 | 1 | 1 |
| Overall Study | Disease progression | 2 | 3 | 1 |
| Overall Study | Moved to local access programme. | 0 | 1 | 1 |
| Overall Study | Physician Decision | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | Cohort 1 | Total | Cohort 2 | Cohort 1a |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants | 18 Participants | 5 Participants | 6 Participants |
| Age, Continuous | 55.0 years STANDARD_DEVIATION 5.23 | 50.3 years STANDARD_DEVIATION 12.04 | 52.2 years STANDARD_DEVIATION 13.82 | 43.0 years STANDARD_DEVIATION 14.1 |
| Cancer Diagnosis Breast | 0 Participants | 4 Participants | 3 Participants | 1 Participants |
| Cancer Diagnosis Cervix | 1 Participants | 2 Participants | 0 Participants | 1 Participants |
| Cancer Diagnosis Head and Neck | 2 Participants | 2 Participants | 0 Participants | 0 Participants |
| Cancer Diagnosis Lung | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Cancer Diagnosis Other; Gallbladder | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Cancer Diagnosis Other; Thymic | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Cancer Diagnosis Ovary | 1 Participants | 2 Participants | 1 Participants | 0 Participants |
| Cancer Diagnosis Pancreas | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Cancer Diagnosis Skin/Soft Tissue | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Cancer Diagnosis Stomach | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Cancer Diagnosis Uterus | 1 Participants | 2 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 19 Participants | 6 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 7 Participants | 19 Participants | 6 Participants | 6 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Australia | 2 Participants | 2 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Japan | 3 Participants | 7 Participants | 1 Participants | 1 Participants |
| Region of Enrollment Korea, Republic Of | 2 Participants | 12 Participants | 5 Participants | 5 Participants |
| Sex: Female, Male Female | 3 Participants | 11 Participants | 5 Participants | 3 Participants |
| Sex: Female, Male Male | 4 Participants | 8 Participants | 1 Participants | 3 Participants |
| Smoking History Current Smoker | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Smoking History Former Smoker | 3 Participants | 7 Participants | 2 Participants | 2 Participants |
| Smoking History Never Used Tobacco | 4 Participants | 11 Participants | 3 Participants | 4 Participants |
| Type of Tobacco Product Used Cigarettes | 3 Participants | 8 Participants | 3 Participants | 2 Participants |
| Type of Tobacco Product Used Cigarillo | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Type of Tobacco Product Used Cigars | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Type of Tobacco Product Used No history of tobacco use | 4 Participants | 11 Participants | 3 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 7 | 1 / 6 | 1 / 6 |
| other Total, other adverse events | 7 / 7 | 6 / 6 | 6 / 6 |
| serious Total, serious adverse events | 3 / 7 | 0 / 6 | 4 / 6 |
Outcome results
Primary
Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term
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.
Time frame: Up to 21 days (1 Cycle)
Population: All patients who received at least one dose of the investigational drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1 | Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term | Alanine aminotransferase increased | 0 Participants |
| Cohort 1 | Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term | Hypocalcaemia | 0 Participants |
| Cohort 1 | Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term | Hypokalemia | 1 Participants |
| Cohort 1 | Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term | Aspartate aminotransferase increased | 0 Participants |
| Cohort 1 | Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term | Hyperglycaemia | 2 Participants |
| Cohort 1 | Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term | Hypophosphatemia | 1 Participants |
| Cohort 1 | Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term | Azotemia | 1 Participants |
| Cohort 1 | Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term | Dehydration | 1 Participants |
| Cohort 1 | Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term | Blood alkaline phosphatase increased | 1 Participants |
| Cohort 1 | Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term | Hypercholsterolaemia | 0 Participants |
| Cohort 1 | Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term | Hypomagnesaemia | 0 Participants |
| Cohort 1 | Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term | Blood lactate dehydrogenase increased | 1 Participants |
| Cohort 1 | Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term | Hypoglycaemia | 1 Participants |
| Cohort 1 | Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term | Hypercalcaemia | 0 Participants |
| Cohort 1 | Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term | C-reactive protein increased | 1 Participants |
| Cohort 1 | Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term | Hepatic function abnormal | 1 Participants |
| Cohort 1 | Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term | Hyponatraemia | 1 Participants |
| Cohort 1 | Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term | Hypoalbuminemia | 2 Participants |
| Cohort 1a | Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term | Blood lactate dehydrogenase increased | 0 Participants |
| Cohort 1a | Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term | Aspartate aminotransferase increased | 2 Participants |
| Cohort 1a | Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term | Alanine aminotransferase increased | 1 Participants |
| Cohort 1a | Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term | Blood alkaline phosphatase increased | 0 Participants |
| Cohort 1a | Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term | C-reactive protein increased | 0 Participants |
| Cohort 1a | Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term | Hypoalbuminemia | 0 Participants |
| Cohort 1a | Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term | Hypokalemia | 1 Participants |
| Cohort 1a | Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term | Hypophosphatemia | 0 Participants |
| Cohort 1a | Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term | Dehydration | 0 Participants |
| Cohort 1a | Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term | Hyperglycaemia | 0 Participants |
| Cohort 1a | Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term | Hypocalcaemia | 0 Participants |
| Cohort 1a | Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term | Hyponatraemia | 0 Participants |
| Cohort 1a | Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term | Hypercalcaemia | 0 Participants |
| Cohort 1a | Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term | Hypercholsterolaemia | 0 Participants |
| Cohort 1a | Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term | Hypoglycaemia | 0 Participants |
| Cohort 1a | Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term | Hypomagnesaemia | 0 Participants |
| Cohort 1a | Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term | Azotemia | 0 Participants |
| Cohort 1a | Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term | Hepatic function abnormal | 0 Participants |
| Cohort 2 | Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term | Hypomagnesaemia | 1 Participants |
| Cohort 2 | Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term | Hyponatraemia | 1 Participants |
| Cohort 2 | Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term | Blood lactate dehydrogenase increased | 0 Participants |
| Cohort 2 | Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term | Alanine aminotransferase increased | 0 Participants |
| Cohort 2 | Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term | Hepatic function abnormal | 0 Participants |
| Cohort 2 | Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term | Hypercholsterolaemia | 1 Participants |
| Cohort 2 | Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term | Hypercalcaemia | 1 Participants |
| Cohort 2 | Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term | Azotemia | 0 Participants |
| Cohort 2 | Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term | Hypophosphatemia | 2 Participants |
| Cohort 2 | Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term | Hypoglycaemia | 0 Participants |
| Cohort 2 | Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term | Dehydration | 1 Participants |
| Cohort 2 | Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term | Hypokalemia | 2 Participants |
| Cohort 2 | Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term | Blood alkaline phosphatase increased | 0 Participants |
| Cohort 2 | Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term | Hyperglycaemia | 0 Participants |
| Cohort 2 | Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term | Hypoalbuminemia | 2 Participants |
| Cohort 2 | Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term | Aspartate aminotransferase increased | 1 Participants |
| Cohort 2 | Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term | Hypocalcaemia | 1 Participants |
| Cohort 2 | Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term | C-reactive protein increased | 0 Participants |
Primary
Number of Patients With Clinically Important Abnormalities in Vital Signs by Preferred Term
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.
Time frame: Up to 21 days (1 Cycle)
Population: All patients who received at least one dose of the investigational drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1 | Number of Patients With Clinically Important Abnormalities in Vital Signs by Preferred Term | Pyrexia | 3 Participants |
| Cohort 1 | Number of Patients With Clinically Important Abnormalities in Vital Signs by Preferred Term | Hypotension | 2 Participants |
| Cohort 1a | Number of Patients With Clinically Important Abnormalities in Vital Signs by Preferred Term | Pyrexia | 1 Participants |
| Cohort 1a | Number of Patients With Clinically Important Abnormalities in Vital Signs by Preferred Term | Hypotension | 0 Participants |
| Cohort 2 | Number of Patients With Clinically Important Abnormalities in Vital Signs by Preferred Term | Pyrexia | 4 Participants |
| Cohort 2 | Number of Patients With Clinically Important Abnormalities in Vital Signs by Preferred Term | Hypotension | 1 Participants |
Primary
Number of Patients With Clinically Important Changes in Haematology and Coagulation TEAEs by System Organ Class and Preferred Term
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.
Time frame: Up to 21 days (1 Cycle)
Population: All patients who received at least one dose of the investigational drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1 | Number of Patients With Clinically Important Changes in Haematology and Coagulation TEAEs by System Organ Class and Preferred Term | BLSD - Febrile Neutropenia | 1 Participants |
| Cohort 1 | 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 |
| Cohort 1 | 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 |
| Cohort 1 | 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 |
| Cohort 1 | 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 |
| Cohort 1 | Number of Patients With Clinically Important Changes in Haematology and Coagulation TEAEs by System Organ Class and Preferred Term | Investigations - Haematocrit Decreased | 1 Participants |
| Cohort 1 | Number of Patients With Clinically Important Changes in Haematology and Coagulation TEAEs by System Organ Class and Preferred Term | BLSD - Thrombocytopenia | 1 Participants |
| Cohort 1 | Number of Patients With Clinically Important Changes in Haematology and Coagulation TEAEs by System Organ Class and Preferred Term | BLSD - Neutropenia | 3 Participants |
| Cohort 1 | 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 |
| Cohort 1a | Number of Patients With Clinically Important Changes in Haematology and Coagulation TEAEs by System Organ Class and Preferred Term | Investigations - WBC Count Decreased | 3 Participants |
| Cohort 1a | 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 | 4 Participants |
| Cohort 1a | Number of Patients With Clinically Important Changes in Haematology and Coagulation TEAEs by System Organ Class and Preferred Term | BLSD - Neutropenia | 0 Participants |
| Cohort 1a | Number of Patients With Clinically Important Changes in Haematology and Coagulation TEAEs by System Organ Class and Preferred Term | BLSD - Thrombocytopenia | 1 Participants |
| Cohort 1a | Number of Patients With Clinically Important Changes in Haematology and Coagulation TEAEs by System Organ Class and Preferred Term | BLSD - Febrile Neutropenia | 0 Participants |
| Cohort 1a | Number of Patients With Clinically Important Changes in Haematology and Coagulation TEAEs by System Organ Class and Preferred Term | Investigations - Neutrophil Count Decreased | 4 Participants |
| Cohort 1a | Number of Patients With Clinically Important Changes in Haematology and Coagulation TEAEs by System Organ Class and Preferred Term | Investigations - Platelet Count Decreased | 3 Participants |
| Cohort 1a | Number of Patients With Clinically Important Changes in Haematology and Coagulation TEAEs by System Organ Class and Preferred Term | Investigations - Haematocrit Decreased | 0 Participants |
| Cohort 1a | Number of Patients With Clinically Important Changes in Haematology and Coagulation TEAEs by System Organ Class and Preferred Term | Investigations - Monocyte Count Decreased | 0 Participants |
| Cohort 2 | Number of Patients With Clinically Important Changes in Haematology and Coagulation TEAEs by System Organ Class and Preferred Term | BLSD - Thrombocytopenia | 2 Participants |
| Cohort 2 | 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 | 5 Participants |
| Cohort 2 | Number of Patients With Clinically Important Changes in Haematology and Coagulation TEAEs by System Organ Class and Preferred Term | Investigations - Platelet Count Decreased | 3 Participants |
| Cohort 2 | Number of Patients With Clinically Important Changes in Haematology and Coagulation TEAEs by System Organ Class and Preferred Term | BLSD - Neutropenia | 2 Participants |
| Cohort 2 | Number of Patients With Clinically Important Changes in Haematology and Coagulation TEAEs by System Organ Class and Preferred Term | Investigations - Monocyte Count Decreased | 0 Participants |
| Cohort 2 | 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 |
| Cohort 2 | Number of Patients With Clinically Important Changes in Haematology and Coagulation TEAEs by System Organ Class and Preferred Term | BLSD - Febrile Neutropenia | 2 Participants |
| Cohort 2 | Number of Patients With Clinically Important Changes in Haematology and Coagulation TEAEs by System Organ Class and Preferred Term | Investigations - Haematocrit Decreased | 0 Participants |
| Cohort 2 | 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 |
Primary
Number of Patients With Treatment-Emergent Adverse Events
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.
Time frame: Up to 21 days (1 Cycle)
Population: All patients who received at least one dose of the investigational drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1 | Number of Patients With Treatment-Emergent Adverse Events | Patients with ≥ 1 Adverse Event (AE) | 7 Participants |
| Cohort 1 | Number of Patients With Treatment-Emergent Adverse Events | Patients with ≥ 1 Treatment-Emergent AE (TEAE) | 6 Participants |
| Cohort 1 | Number of Patients With Treatment-Emergent Adverse Events | Patients with TEAE Related to Treatment | 6 Participants |
| Cohort 1 | Number of Patients With Treatment-Emergent Adverse Events | Patients with Serious TEAE | 3 Participants |
| Cohort 1 | Number of Patients With Treatment-Emergent Adverse Events | Patients with Severe TEAE | 6 Participants |
| Cohort 1 | Number of Patients With Treatment-Emergent Adverse Events | Patients with TEAE with AZD1775 discontinued | 1 Participants |
| Cohort 1 | Number of Patients With Treatment-Emergent Adverse Events | Patients with TEAE with paclitaxel discontinued | 1 Participants |
| Cohort 1 | Number of Patients With Treatment-Emergent Adverse Events | Patients with TEAE with carboplatin discontinued | 0 Participants |
| Cohort 1 | Number of Patients With Treatment-Emergent Adverse Events | Patients with TEAE and fatal outcome | 1 Participants |
| Cohort 1 | Number of Patients With Treatment-Emergent Adverse Events | Patients with Dose-Limiting Toxicity | 1 Participants |
| Cohort 1a | Number of Patients With Treatment-Emergent Adverse Events | Patients with TEAE and fatal outcome | 0 Participants |
| Cohort 1a | Number of Patients With Treatment-Emergent Adverse Events | Patients with ≥ 1 Adverse Event (AE) | 6 Participants |
| Cohort 1a | Number of Patients With Treatment-Emergent Adverse Events | Patients with TEAE with AZD1775 discontinued | 0 Participants |
| Cohort 1a | Number of Patients With Treatment-Emergent Adverse Events | Patients with Severe TEAE | 4 Participants |
| Cohort 1a | Number of Patients With Treatment-Emergent Adverse Events | Patients with ≥ 1 Treatment-Emergent AE (TEAE) | 6 Participants |
| Cohort 1a | Number of Patients With Treatment-Emergent Adverse Events | Patients with Dose-Limiting Toxicity | 1 Participants |
| Cohort 1a | Number of Patients With Treatment-Emergent Adverse Events | Patients with TEAE with carboplatin discontinued | 0 Participants |
| Cohort 1a | Number of Patients With Treatment-Emergent Adverse Events | Patients with TEAE Related to Treatment | 4 Participants |
| Cohort 1a | Number of Patients With Treatment-Emergent Adverse Events | Patients with TEAE with paclitaxel discontinued | NA Participants |
| Cohort 1a | Number of Patients With Treatment-Emergent Adverse Events | Patients with Serious TEAE | 0 Participants |
| Cohort 2 | Number of Patients With Treatment-Emergent Adverse Events | Patients with TEAE with carboplatin discontinued | 2 Participants |
| Cohort 2 | Number of Patients With Treatment-Emergent Adverse Events | Patients with Serious TEAE | 4 Participants |
| Cohort 2 | Number of Patients With Treatment-Emergent Adverse Events | Patients with Severe TEAE | 6 Participants |
| Cohort 2 | Number of Patients With Treatment-Emergent Adverse Events | Patients with TEAE with AZD1775 discontinued | 2 Participants |
| Cohort 2 | Number of Patients With Treatment-Emergent Adverse Events | Patients with TEAE and fatal outcome | 1 Participants |
| Cohort 2 | Number of Patients With Treatment-Emergent Adverse Events | Patients with TEAE with paclitaxel discontinued | 2 Participants |
| Cohort 2 | Number of Patients With Treatment-Emergent Adverse Events | Patients with ≥ 1 Adverse Event (AE) | 6 Participants |
| Cohort 2 | Number of Patients With Treatment-Emergent Adverse Events | Patients with Dose-Limiting Toxicity | 2 Participants |
| Cohort 2 | Number of Patients With Treatment-Emergent Adverse Events | Patients with ≥ 1 Treatment-Emergent AE (TEAE) | 6 Participants |
| Cohort 2 | Number of Patients With Treatment-Emergent Adverse Events | Patients with TEAE Related to Treatment | 6 Participants |
Primary
Number of Patients With Treatment-Emergent Adverse Events During AZD1775 Monotherapy Cycle by System Organ Class and Preferred Term
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.
Time frame: Up to 1 week
Population: All patients who received at least one dose of the investigational drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1 | Number of Patients With Treatment-Emergent Adverse Events During AZD1775 Monotherapy Cycle by System Organ Class and Preferred Term | Gastrointestinal Disorders - Diarrhoea | 0 Participants |
| Cohort 1 | Number of Patients With Treatment-Emergent Adverse Events During AZD1775 Monotherapy Cycle by System Organ Class and Preferred Term | Gastrointestinal Disorders - Constipation | 0 Participants |
| Cohort 1 | 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 |
| Cohort 1 | Number of Patients With Treatment-Emergent Adverse Events During AZD1775 Monotherapy Cycle by System Organ Class and Preferred Term | Gastrointestinal Disorders - Nausea | 1 Participants |
| Cohort 1 | 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 |
| Cohort 1a | Number of Patients With Treatment-Emergent Adverse Events During AZD1775 Monotherapy Cycle by System Organ Class and Preferred Term | Gastrointestinal Disorders - Constipation | 0 Participants |
| Cohort 1a | 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 |
| Cohort 1a | Number of Patients With Treatment-Emergent Adverse Events During AZD1775 Monotherapy Cycle by System Organ Class and Preferred Term | Gastrointestinal Disorders - Nausea | 1 Participants |
| Cohort 1a | Number of Patients With Treatment-Emergent Adverse Events During AZD1775 Monotherapy Cycle by System Organ Class and Preferred Term | Gastrointestinal Disorders - Diarrhoea | 1 Participants |
| Cohort 1a | 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 |
| Cohort 2 | Number of Patients With Treatment-Emergent Adverse Events During AZD1775 Monotherapy Cycle by System Organ Class and Preferred Term | Immune System Disorders - Hypersensitivity | 1 Participants |
| Cohort 2 | Number of Patients With Treatment-Emergent Adverse Events During AZD1775 Monotherapy Cycle by System Organ Class and Preferred Term | Gastrointestinal Disorders - Diarrhoea | 0 Participants |
| Cohort 2 | 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 | 2 Participants |
| Cohort 2 | Number of Patients With Treatment-Emergent Adverse Events During AZD1775 Monotherapy Cycle by System Organ Class and Preferred Term | Gastrointestinal Disorders - Constipation | 1 Participants |
| Cohort 2 | Number of Patients With Treatment-Emergent Adverse Events During AZD1775 Monotherapy Cycle by System Organ Class and Preferred Term | Gastrointestinal Disorders - Nausea | 1 Participants |
Primary
Number of Treatment-Emergent Adverse Events (TEAE)
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.
Time frame: Up to 21 days (1 Cycle)
Population: All patients who received at least one dose of the investigational drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1 | Number of Treatment-Emergent Adverse Events (TEAE) | Number of Adverse Events (AEs) | 370 TEAE |
| Cohort 1 | Number of Treatment-Emergent Adverse Events (TEAE) | Number of TEAEs with paclitaxel discontinued | 1 TEAE |
| Cohort 1 | Number of Treatment-Emergent Adverse Events (TEAE) | Number of Severe TEAEs | 88 TEAE |
| Cohort 1 | Number of Treatment-Emergent Adverse Events (TEAE) | Number of Dose-Limiting Toxicities (DLT) | 1 TEAE |
| Cohort 1 | Number of Treatment-Emergent Adverse Events (TEAE) | Number of TEAEs with AZD1775 discontinued | 3 TEAE |
| Cohort 1 | Number of Treatment-Emergent Adverse Events (TEAE) | Number of TEAEs with fatal outcome | 1 TEAE |
| Cohort 1 | Number of Treatment-Emergent Adverse Events (TEAE) | Number of TEAEs | 362 TEAE |
| Cohort 1 | Number of Treatment-Emergent Adverse Events (TEAE) | Number of Serious TEAEs | 9 TEAE |
| Cohort 1 | Number of Treatment-Emergent Adverse Events (TEAE) | Number of TEAEs with carboplatin discontinued | 0 TEAE |
| Cohort 1 | Number of Treatment-Emergent Adverse Events (TEAE) | Number of TEAEs Related to Study Treatment | 262 TEAE |
| Cohort 1 | Number of Treatment-Emergent Adverse Events (TEAE) | Number of TEAEs with DLT | 1 TEAE |
| Cohort 1a | Number of Treatment-Emergent Adverse Events (TEAE) | Number of TEAEs Related to Study Treatment | 95 TEAE |
| Cohort 1a | Number of Treatment-Emergent Adverse Events (TEAE) | Number of Adverse Events (AEs) | 202 TEAE |
| Cohort 1a | Number of Treatment-Emergent Adverse Events (TEAE) | Number of TEAEs | 182 TEAE |
| Cohort 1a | Number of Treatment-Emergent Adverse Events (TEAE) | Number of Serious TEAEs | 0 TEAE |
| Cohort 1a | Number of Treatment-Emergent Adverse Events (TEAE) | Number of Severe TEAEs | 23 TEAE |
| Cohort 1a | Number of Treatment-Emergent Adverse Events (TEAE) | Number of TEAEs with AZD1775 discontinued | 0 TEAE |
| Cohort 1a | Number of Treatment-Emergent Adverse Events (TEAE) | Number of TEAEs with paclitaxel discontinued | NA TEAE |
| Cohort 1a | Number of Treatment-Emergent Adverse Events (TEAE) | Number of TEAEs with carboplatin discontinued | 0 TEAE |
| Cohort 1a | Number of Treatment-Emergent Adverse Events (TEAE) | Number of TEAEs with fatal outcome | 0 TEAE |
| Cohort 1a | Number of Treatment-Emergent Adverse Events (TEAE) | Number of Dose-Limiting Toxicities (DLT) | 1 TEAE |
| Cohort 1a | Number of Treatment-Emergent Adverse Events (TEAE) | Number of TEAEs with DLT | 1 TEAE |
| Cohort 2 | Number of Treatment-Emergent Adverse Events (TEAE) | Number of TEAEs | 381 TEAE |
| Cohort 2 | Number of Treatment-Emergent Adverse Events (TEAE) | Number of TEAEs with DLT | 2 TEAE |
| Cohort 2 | Number of Treatment-Emergent Adverse Events (TEAE) | Number of TEAEs with carboplatin discontinued | 3 TEAE |
| Cohort 2 | Number of Treatment-Emergent Adverse Events (TEAE) | Number of Adverse Events (AEs) | 382 TEAE |
| Cohort 2 | Number of Treatment-Emergent Adverse Events (TEAE) | Number of Dose-Limiting Toxicities (DLT) | 2 TEAE |
| Cohort 2 | Number of Treatment-Emergent Adverse Events (TEAE) | Number of Severe TEAEs | 101 TEAE |
| Cohort 2 | Number of Treatment-Emergent Adverse Events (TEAE) | Number of TEAEs with fatal outcome | 2 TEAE |
| Cohort 2 | Number of Treatment-Emergent Adverse Events (TEAE) | Number of TEAEs with AZD1775 discontinued | 3 TEAE |
| Cohort 2 | Number of Treatment-Emergent Adverse Events (TEAE) | Number of Serious TEAEs | 9 TEAE |
| Cohort 2 | Number of Treatment-Emergent Adverse Events (TEAE) | Number of TEAEs Related to Study Treatment | 263 TEAE |
| Cohort 2 | Number of Treatment-Emergent Adverse Events (TEAE) | Number of TEAEs with paclitaxel discontinued | 3 TEAE |
Secondary
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)
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | 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 |
| Cohort 1a | 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) | 44630 h*ng/mL | Geometric Coefficient of Variation 2.552 |
| Cohort 2 | 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) | 51340 h*ng/mL | Geometric Coefficient of Variation 12.24 |
Secondary
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)
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | 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 |
| Cohort 1a | 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) | 48700 h*ng/mL | Geometric Coefficient of Variation 0 |
Secondary
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
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | 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 |
| Cohort 2 | 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 | 16360 h*ng/mL | Geometric Coefficient of Variation 20.11 |
Secondary
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)
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | 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 |
| Cohort 1a | 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) | 7154 nM*h | Geometric Coefficient of Variation 32.29 |
| Cohort 2 | 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) | 14870 nM*h | Geometric Coefficient of Variation 34.05 |
Secondary
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
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | 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 |
| Cohort 1a | 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 | 3387 nM*h | Geometric Coefficient of Variation 12.54 |
| Cohort 2 | 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 | 5331 nM*h | Geometric Coefficient of Variation 37.42 |
Secondary
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)
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | 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 |
| Cohort 1a | 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) | 2902 nM*h | Geometric Coefficient of Variation 33.21 |
| Cohort 2 | 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) | 5606 nM*h | Geometric Coefficient of Variation 20.02 |
Secondary
Best Overall Response
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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1 | Best Overall Response | Progressive Disease | 2 Participants |
| Cohort 1 | Best Overall Response | Stable Disease | 2 Participants |
| Cohort 1 | Best Overall Response | Partial Response | 1 Participants |
| Cohort 1 | Best Overall Response | Not Evaluable | 1 Participants |
| Cohort 1 | Best Overall Response | Complete Response | 0 Participants |
| Cohort 1a | Best Overall Response | Stable Disease | 2 Participants |
| Cohort 1a | Best Overall Response | Partial Response | 1 Participants |
| Cohort 1a | Best Overall Response | Not Evaluable | 2 Participants |
| Cohort 1a | Best Overall Response | Progressive Disease | 1 Participants |
| Cohort 1a | Best Overall Response | Complete Response | 0 Participants |
| Cohort 2 | Best Overall Response | Complete Response | 0 Participants |
| Cohort 2 | Best Overall Response | Progressive Disease | 0 Participants |
| Cohort 2 | Best Overall Response | Partial Response | 3 Participants |
| Cohort 2 | Best Overall Response | Stable Disease | 2 Participants |
| Cohort 2 | Best Overall Response | Not Evaluable | 1 Participants |
Secondary
Duration of Response
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.
Time frame: Up to 18 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 | Duration of Response | 18.1 Weeks |
| Cohort 1a | Duration of Response | 0.00 Weeks |
| Cohort 2 | Duration of Response | 20.7 Weeks |
Secondary
Number of Patients With an Objective Response
Objective response is defined as either a complete response or a partial response.
Time frame: Up to 18 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 | Number of Patients With an Objective Response | 1 Participants |
| Cohort 1a | Number of Patients With an Objective Response | 1 Participants |
| Cohort 2 | Number of Patients With an Objective Response | 3 Participants |
Secondary
Number of Patients With Clinical Benefit
Clinical benefit is defined as achieving complete response, partial response, or stable disease.
Time frame: Up to 18 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 | Number of Patients With Clinical Benefit | 3 Participants |
| Cohort 1a | Number of Patients With Clinical Benefit | 3 Participants |
| Cohort 2 | Number of Patients With Clinical Benefit | 5 Participants |
Secondary
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)
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | 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 |
| Cohort 1a | 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) | 1129 nM | Geometric Coefficient of Variation 25.51 |
| Cohort 2 | 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) | 2289 nM | Geometric Coefficient of Variation 32.82 |
Secondary
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)
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | 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 |
| Cohort 1a | 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) | 654.8 nM | Geometric Coefficient of Variation 32.27 |
| Cohort 2 | 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) | 1133 nM | Geometric Coefficient of Variation 16.3 |
Secondary
Peak Plasma Concentration (Cmax) of AZD1775 Following Single Dose Administration of AZD1775 Monotherapy
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | Peak Plasma Concentration (Cmax) of AZD1775 Following Single Dose Administration of AZD1775 Monotherapy | 689.1 nM | Geometric Coefficient of Variation 51.79 |
| Cohort 1a | Peak Plasma Concentration (Cmax) of AZD1775 Following Single Dose Administration of AZD1775 Monotherapy | 649.2 nM | Geometric Coefficient of Variation 10.74 |
| Cohort 2 | Peak Plasma Concentration (Cmax) of AZD1775 Following Single Dose Administration of AZD1775 Monotherapy | 1066 nM | Geometric Coefficient of Variation 38 |
Secondary
Peak Plasma Concentration (Cmax) of Paclitaxel Following Single IV Infusion in Combination With Single Dose Oral AZD1775 and IV Carboplatin
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | 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 |
| Cohort 2 | Peak Plasma Concentration (Cmax) of Paclitaxel Following Single IV Infusion in Combination With Single Dose Oral AZD1775 and IV Carboplatin | 5361 ng/mL | Geometric Coefficient of Variation 4.744 |
Secondary
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)
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | 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 |
| Cohort 1a | 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) | 18550 ng/mL | Geometric Coefficient of Variation 19.87 |
| Cohort 2 | 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) | 17500 ng/mL | Geometric Coefficient of Variation 34.93 |
Secondary
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)
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | 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 |
| Cohort 1a | 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) | 13200 ng/mL | Geometric Coefficient of Variation 0 |
Secondary
Percentage of Patients With an Objective Response
Objective response is defined as either a complete response or a partial response.
Time frame: Up to 18 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 | Percentage of Patients With an Objective Response | 16.7 Percentage |
| Cohort 1a | Percentage of Patients With an Objective Response | 16.7 Percentage |
| Cohort 2 | Percentage of Patients With an Objective Response | 50 Percentage |
Secondary
Percentage of Patients With Clinical Benefit
Clinical benefit is defined as achieving complete response, partial response, or stable disease.
Time frame: Up to 18 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 | Percentage of Patients With Clinical Benefit | 50 Percentage |
| Cohort 1a | Percentage of Patients With Clinical Benefit | 50 Percentage |
| Cohort 2 | Percentage of Patients With Clinical Benefit | 83.3 Percentage |
Secondary
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)
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | 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 |
| Cohort 1a | 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) | 774.6 nM | Geometric Coefficient of Variation 32.96 |
| Cohort 2 | 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) | 1700 nM | Geometric Coefficient of Variation 37.6 |
Secondary
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)
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | 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 |
| Cohort 1a | 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) | 378.2 nM | Geometric Coefficient of Variation 27.61 |
| Cohort 2 | 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) | 805.9 nM | Geometric Coefficient of Variation 27.5 |
Secondary
Plasma Concentration of AZD1775 8 Hours After Single Dose Administration (C8h) of AZD1775 Monotherapy
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | Plasma Concentration of AZD1775 8 Hours After Single Dose Administration (C8h) of AZD1775 Monotherapy | 370.1 nM | Geometric Coefficient of Variation 29.15 |
| Cohort 1a | Plasma Concentration of AZD1775 8 Hours After Single Dose Administration (C8h) of AZD1775 Monotherapy | 343.5 nM | Geometric Coefficient of Variation 29.97 |
| Cohort 2 | Plasma Concentration of AZD1775 8 Hours After Single Dose Administration (C8h) of AZD1775 Monotherapy | 612 nM | Geometric Coefficient of Variation 36.6 |
Secondary
Plasma Concentration of Paclitaxel at the End of Infusion (Ceoi) When Given Combination With Oral AZD1775 and IV Carboplatin.
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | 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 |
| Cohort 2 | Plasma Concentration of Paclitaxel at the End of Infusion (Ceoi) When Given Combination With Oral AZD1775 and IV Carboplatin. | 5361 ng/mL | Geometric Coefficient of Variation 4.744 |
Secondary
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.
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | 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 |
| Cohort 1a | 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. | 18550 ng/mL | Geometric Coefficient of Variation 19.87 |
| Cohort 2 | 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. | 17500 ng/mL | Geometric Coefficient of Variation 34.93 |
Secondary
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.
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 | 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 |
| Cohort 1a | 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. | 12200 ng/mL | Geometric Coefficient of Variation 0 |
Secondary
Time to Last Detectable Concentration of Platinum (Tlast) When Given as a 1 Hour Infusion in Combination With Oral AZD1775 and IV Paclitaxel.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 | 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 |
| Cohort 1a | Time to Last Detectable Concentration of Platinum (Tlast) When Given as a 1 Hour Infusion in Combination With Oral AZD1775 and IV Paclitaxel. | 7.28 hours |
| Cohort 2 | Time to Last Detectable Concentration of Platinum (Tlast) When Given as a 1 Hour Infusion in Combination With Oral AZD1775 and IV Paclitaxel. | 8.00 hours |
Secondary
Time to Last Detectable Concentration of Platinum (Tlast) When Given as a 2 Hour Infusion in Combination With Oral AZD1775 and IV Paclitaxel.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 | 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 |
| Cohort 1a | Time to Last Detectable Concentration of Platinum (Tlast) When Given as a 2 Hour Infusion in Combination With Oral AZD1775 and IV Paclitaxel. | 8.00 hours |
Secondary
Time to Last Detectable Concentration (Tlast) of Paclitaxel When Given in Combination With Oral AZD1775 and IV Carboplatin
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 | Time to Last Detectable Concentration (Tlast) of Paclitaxel When Given in Combination With Oral AZD1775 and IV Carboplatin | 2.99 hours |
| Cohort 2 | Time to Last Detectable Concentration (Tlast) of Paclitaxel When Given in Combination With Oral AZD1775 and IV Carboplatin | 3.03 hours |
Secondary
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)
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 | 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 |
| Cohort 1a | 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) | 3.09 hours |
| Cohort 2 | 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) | 4.04 hours |
Secondary
Time to Maximum Plasma Concentration (Tmax) of AZD1775 Following Single Dose Administration of AZD1775 Monotherapy
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 | Time to Maximum Plasma Concentration (Tmax) of AZD1775 Following Single Dose Administration of AZD1775 Monotherapy | 2.02 hours |
| Cohort 1a | Time to Maximum Plasma Concentration (Tmax) of AZD1775 Following Single Dose Administration of AZD1775 Monotherapy | 3.95 hours |
| Cohort 2 | Time to Maximum Plasma Concentration (Tmax) of AZD1775 Following Single Dose Administration of AZD1775 Monotherapy | 3.96 hours |
Secondary
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)
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 | 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 |
| Cohort 1a | 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) | 4.04 hours |
| Cohort 2 | 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 |
Secondary
Time to Maximum Plasma Concentration (Tmax) of IV Paclitaxel When Given in Combination With Oral AZD1775 and IV Carboplatin
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 | Time to Maximum Plasma Concentration (Tmax) of IV Paclitaxel When Given in Combination With Oral AZD1775 and IV Carboplatin | 2.99 hours |
| Cohort 2 | Time to Maximum Plasma Concentration (Tmax) of IV Paclitaxel When Given in Combination With Oral AZD1775 and IV Carboplatin | 3.03 hours |
Secondary
Time to Peak Plasma Concentration of Platinum (Tmax) When Given as a 1 Hour Infusion in Combination With Oral AZD1775 and IV Paclitaxel.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 | 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 |
| Cohort 1a | 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 |
| Cohort 2 | 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 |
Secondary
Time to Peak Plasma Concentration of Platinum (Tmax) When Given as a 2 Hour Infusion in Combination With Oral AZD1775 and IV Paclitaxel.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 | 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 |
| Cohort 1a | Time to Peak Plasma Concentration of Platinum (Tmax) When Given as a 2 Hour Infusion in Combination With Oral AZD1775 and IV Paclitaxel. | 1.08 hours |