Ovarian, Fallopian Tube, Peritoneal Cancer, P53 Mutation
Conditions
Keywords
Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
Brief summary
Adavosertib in combination with carboplatin, paclitaxel, gemcitabine, or PLD.
Detailed description
This is an open-label, four-arm lead-in safety and efficacy study in which adavosertib will be combined in four separate treatment arms as follows: adavosertib plus gemcitabine (Arm A); adavosertib plus weekly paclitaxel (Arm B); adavosertib plus carboplatin (Arm C); and adavosertib plus PLD (Arm D). A subset of patients will be evaluated for the safety assessment of each treatment arm. The adavosertib plus paclitaxel arm (Arm B) will enrol approximately 30 additional patients at selected sites as part of a further efficacy evaluation based on emerging data that suggests clinical activity. In addition, the adavosertib plus carboplatin arm (Arm C) will enrol approximately 23 patients overall at selected sites as part of a further efficacy evaluation based on emerging data that suggests clinical activity. To further optimise the dosing schedule of adavosertib in Arm C, a safety expansion arm (referred to as Arm C2) of approximately 12 additional patients will be enrolled at selected sites to explore emerging pre-clinical and clinical data that suggest that prolonged adavosertib exposure may increase the clinical activity.
Interventions
DRUGPLD
PLD (pegylated liposomal doxorubicin) 40 mg/m² IV will be given on Day 1 of each 28-Day cycle.
DRUGAdavosertib
Adavosertib will be taken as oral capsules with water, approx. 2 hours before or 2 hours after food.
DRUGPaclitaxel
Paclitaxel will be administered as a 1-hour IV infusion (± 10 minutes) at a dose of 80 mg/m2 according to institutional standards on Days 1, 8, and 15 of each 28 Day cycle. Patients should be pre-medicated with corticosteroids, diphenhydramine and/or H2 antagonists according to institutional standards.
DRUGCarboplatin
Carboplatin, at a dose calculated to produce an AUC of 5 will be administered by intravenous infusion according to institutional standards on Day 1 of each 21 Day cycle. The carboplatin dose will be calculated using the Calvert Formula based on the patient's glomerular filtration rate (GFR) which is estimated by using the creatinine clearance.
DRUGGemcitabine
Gemcitabine 800 mg/m² will be administered IV on Days 1, 8, and 15 of each 28-Day cycle.
Sponsors
AstraZeneca
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 130 Years
Healthy volunteers
No
Inclusion criteria
Inclusion * Has read and understands the informed consent form (ICF) and has given written IC prior to any study specific procedures. * Histologic or cytologic diagnosis of epithelial ovarian, fallopian tube, or primary peritoneal cancer. * Progressed within 6 months of completing at least 4 cycles of a first-line platinum-containing regimen for Stage III/IV disease. Patients with refractory disease (progression during platinum-containing therapy) are ineligible. * No more than 2-4 prior treatment regimens for Stage III/IV disease, defined as investigational, chemotherapy, hormonal, biologic, or targeted therapy. * Prior doxorubicin (or other anthracycline) at a cumulative dose of ≤ 360 mg/m² or cumulative epirubicin dose of ≤ 720 mg/m² (calculated using doxorubicin equivalent doses: 1 mg of doxorubicin = 1 mg PLD = 0.3 mg mitoxantrone = 0.25 mg idarubicin). Subjects without any prior anthracycline exposure can also be included. Applies to Arm D only. * At least 1 measurable lesion according to RECIST v1.1. * Any prior palliative radiation therapy must be completed at least 7 days prior to start of study treatment and patients must have recovered from any acute adverse effects prior to start of study treatment. * Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 - 1. * Baseline Laboratory Values: 1. ANC ≥1500/μL 2. HgB ≥ 9 g/dL with no blood transfusions in the past 28 days 3. Platelets ≥ 100,000/μL 4. ALT & AST ≤3 x ULN or ≤5 x ULN if known hepatic metastases 5. Serum bilirubin within normal limits (WNL) or ≤1.5 x the ULN in patients with liver metastases; or total bilirubin ≤3.0 x ULN with direct bilirubin WNL in patients with well documented Gilbert's Syndrome. 6. Serum creatinine ≤1.5 x the ULN and a calculated creatinine clearance (CrCl) ≥45 mL/min by the Cockcroft-Gault method. * Left ventricular ejection fraction (LVEF) WNL of the institution as determined by multiple uptake gated acquisition (MUGA) or echocardiography (ECHO) (applies to Arm D only). * Female patients, ≥18, (not of childbearing potential and fertile female patients of childbearing potential) who agree to use adequate contraceptive measures from 2 weeks prior to the study and until 1 month after study treatment discontinuation, who are not breastfeeding, and who have a negative serum or urine pregnancy test within 72 hours prior to start. * Predicted life expectancy ≥ 12 weeks Exclusion * Use of a study drug (approved or investigational drug therapy) ≤21 days or 5 half-lives (whichever is shorter) prior to the first dose of study treatment. For study drugs for which 5 half-lives is ≤21 days, a minimum of 10 days between termination of the study drug and administration of study treatment is required. * Major surgical procedures ≤ 28 days of beginning study, or minor surgical procedures ≤ 7 days. No waiting period following port-a-cath placement, or any other central venous access placement. * Grade \>1 toxicity from prior therapy (except alopecia or anorexia). * Known malignant CNS disease other than neurologically stable, treated brain metastases, defined as metastasis having no evidence of progression or haemorrhage after treatment for at least 2 weeks (including brain radiotherapy). Must be off any systemic corticosteroids for the treatment of brain metastases for at least 14 days prior to enrolment. * Patient has had prescription or non-prescription drugs or other products (i.e. grapefruit juice) known to be sensitive 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 prior to Day 1 of dosing and withheld throughout the study until 2 weeks after last dose of study drug. * Caution should be exercised when inhibitors or substrates of P-gP, substrates of CYP1A2 with a narrow therapeutic range, sensitive substrates of CYP2C19 or CYP2C19 substrates with a narrow therapeutic range are administered with adavosertib. * Herbal medications should be discontinued 7 days prior to the first dose of study treatment. * Any of the following cardiac diseases currently or within the last 6 months as defined by New York Heart Association (NYHA) ≥ Class 2: 1. Unstable angina pectoris 2. Congestive heart failure 3. Acute myocardial infarction 4. Conduction abnormality not controlled with pacemaker or medication 5. Significant ventricular or supraventricular arrhythmias (patients with chronic rate controlled atrial fibrillation in the absence of other cardiac abnormalities are eligible). * Adavosertib should not be given to patients who have a history of Torsades de pointes unless all risk factors that contributed to Torsades have been corrected. Adavosertib has not been studied in patients with ventricular arrhythmias or recent myocardial infarction. * Corrected QT interval (QTc) \>470 msec at study entry or congenital long QT syndrome. * Pregnant or lactating. * Serious active infection at the time of enrolment, or another serious underlying medical condition that would impair the patient's ability to receive study treatment. * Presence of other active cancers, or history of treatment for invasive cancer within 3 years. Patients with Stage I cancer who have received definitive local treatment within 3 years, and whom are considered unlikely to recur, are eligible. Patients with previously treated in-situ carcinoma (i.e., non-invasive) are eligible, as are patients with prior non-melanoma skin cancers.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | Throughout the duration of the study (up to 19 months) | Objective response rate is defined as the proportion of patients achieving a complete or partial tumour response according to RECIST v1.1 criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response (DoR) | Throughout the duration of the study, approximately 19 months. | Duration of Response (DoR) is defined as the time from first documented tumour response until the date of documented progression or death from any cause. |
| Progression Free Survival (Median, 80% CI) | Throughout the Study, Approximately 4 years | Progression-free survival (PFS) was defined as the elapsed time from date of first dose of AZD1775 until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdrew from therapy or received another anti-cancer therapy prior to progression. Patients who had not progressed or died at the time of analysis were censored at the time of the latest date of assessment from their last evaluable RECIST assessment. Progression-free survival was derived based on scan/assessment dates, not visit dates. |
| Progression Free Survival (Median, 95% CI) | Throughout the Study, Approximately 4 years | Progression-free survival (PFS) was defined as the elapsed time from date of first dose of AZD1775 until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdrew from therapy or received another anti-cancer therapy prior to progression. Patients who had not progressed or died at the time of analysis were censored at the time of the latest date of assessment from their last evaluable RECIST assessment. Progression-free survival was derived based on scan/assessment dates, not visit dates. |
| Overall Survival (Median, 80% CI) | Throughout the Study, Approximately 4 years | Overall survival (OS) was defined as the elapsed time from the date of first dose of AZD1775 until death due to any cause. Any patient not known to have died at the time of the analysis was censored based on the last recorded date on which the patient was known to be alive. |
| Overall Survival (Median, 95% CI) | Throughout the Study, Approximately 4 years | Overall survival (OS) was defined as the elapsed time from the date of first dose of AZD1775 until death due to any cause. Any patient not known to have died at the time of the analysis was censored based on the last recorded date on which the patient was known to be alive. |
| Gynecologic Cancer Intergroup (GCIG) CA-125 Response | Throughout the study, approximately 4 years | The GCIG CA-125 response is defined as the proportion of patients achieving a 50% reduction in CA-125 levels from baseline, if baseline level is ≥2 x the upper limit of normal (ULN) within 2 weeks prior to starting treatment. Response must be confirmed and maintained for at least 28 days. |
| The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) by Maximum CTCAE Grade. | Throughout the duration of the study (up to 19 months) | The number of patients experiencing at least one treatment-related adverse event (TEAE) by maximum CTCAE grade. Severity Grade 1 = Mild; Severity Grade 2 = Moderate; Severity Grade 3 = Severe; Severity Grade 4 = Life Threatening; Severity Grade 5 = Fatal |
| The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Adavosertib by Maximum CTCAE Grade | Throughout the duration of the study (up to 19 months) | The number and proportion of patients experiencing at least one treatment-related adverse event (TEAE) related to adavosertib by maximum CTCAE grade Severity Grade 1 = Mild; Severity Grade 2 = Moderate; Severity Grade 3 = Severe; Severity Grade 4 = Life Threatening; Severity Grade 5 = Fatal |
| The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Chemotherapy by Maximum CTCAE Grade | Throughout the duration of the study (up to 19 months) | The number of patients experiencing at least one treatment-related adverse event (TEAE) related to chemotherapy by maximum CTCAE grade. Severity Grade 1 = Mild; Severity Grade 2 = Moderate; Severity Grade 3 = Severe; Severity Grade 4 = Life Threatening; Severity Grade 5 = Fatal |
| Serious Adverse Events | Throughout the duration of the study (up to 19 months) | The number of patients experiencing at least one serious adverse event (SAE). |
| Disease Control Rate (DCR) | Throughout the duration of the study (up to 19 months) | The Disease Control Rate is defined as the proportion of patients achieving a complete response (CR), partial response (PR), or stable disease (SD) according to RECIST v1.1 criteria. |
| Treatment-Related Adverse Events Related to Adavosertib Leading to Treatment Discontinuation | Throughout the duration of the study (up to 19 months) | The number of patients experiencing at least one treatment-related adverse event related to adavosertib leading to treatment discontinuation. |
| Treatment-Related Adverse Events Related to Adavosertib Leading to Dose Reduction | Throughout the duration of the study (up to 19 months) | The number of patients experiencing at least one treatment-related adverse event related to adavosertib leading to dose reduction. |
| Treatment-Related Adverse Events Related to Adavosertib Leading to Treatment Interruption | Throughout the duration of the study (up to 19 months) | The number of patients experiencing at least one treatment-related adverse event related to adavosertib leading to treatment interruption. |
| Treatment-Related Adverse Events Related to Chemotherapy Leading to Treatment Discontinuation | Throughout the duration of the study (up to 19 months) | The number of patients experiencing at least one treatment-related adverse event related to chemotherapy leading to treatment discontinuation. |
| Treatment-Related Adverse Events Related to Chemotherapy Leading to Dose Reduction | Throughout the duration of the study (up to 19 months) | The number of patients experiencing at least one treatment-related adverse event related to chemotherapy leading to dose reduction. |
| Treatment-Related Adverse Events Related to Chemotherapy Leading to Treatment Interruption | Throughout the duration of the study (up to 19 months) | The number of patients experiencing at least one treatment-related adverse event related to chemotherapy leading to treatment interruption. |
| Single Dose Adavosertib Cmax | Pre-dose, 0.5 hr, 1 hr, 2 hr, 4 hr, 6 hr, and 8 hr | Maximum plasma concentration of adavosertib after a single oral dose (Cycle 1 Day 1) in combination with IV infusion of commonly used chemotherapy agents, including gemcitabine, paclitaxel, and carboplatin. |
| Multiple Dose Adavosertib Cmax | Pre-dose, 1 hr, 2 hr, 4 hr, 6 hr, and 8 hr | Maximum plasma concentration of adavosertib after a multiple oral doses (Cycle 1 Day 3) in combination with IV infusion of 40 mg/m² pegylated liposomal doxorubicin. |
| Single Dose Adavosertib Tmax | Pre-dose, 0.5 hr, 1 hr, 2 hr, 4 hr, 6 hr, and 8 hr | The time to reach maximum plasma concentration of adavosertib after a single oral dose (Cycle 1 Day 1) in combination with IV infusion of commonly used chemotherapy agents, including gemcitabine, paclitaxel, and carboplatin. |
| Multiple Dose Adavosertib Tmax | Pre-dose, 1 hr, 2 hr, 4 hr, 6 hr, and 8 hr | The time to reach maximum plasma concentration of adavosertib after multiple oral doses (Cycle 1 Day 3) in combination with IV infusion of 40 mg/m² pegylated liposomal doxorubicin. |
| Serious Adverse Events Leading to Death | Throughout the duration of the study (up to 19 months) | The number of patients experiencing at least one serious adverse event (SAE) leading to death. |
Countries
Canada, Netherlands, United States
Participant flow
Recruitment details
This multi-center study was conducted at 20 sites: 18 in the USA, 1 in Canada, and 1 in The Netherlands. Ninety-five (95) patients were enrolled; 94 patients received treatment. The first patient started treatment on 2 Feb 2015; the final patients were still receiving treatment and were censored at the time of database lock on 14 Dec 2018.
Pre-assignment details
One hundred twenty-six (126) patients consented and underwent screening; 94 patients passed screening, whereas 32 patients failed screening tests and were not eligible. The Full Analysis Set consists of 94 patients.
Participants by arm
| Arm | Count |
|---|---|
| Arm A Adavosertib 175 mg orally QD on Days 1, 2, 8, 9, 15, and 16 of 28 day cycles.
Gemcitabine 800 mg/m² IV on Days 1, 8, and 15 of 28 day cycles. | 9 |
| Arm B Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 28 day cycles.
Paclitaxel 80 mg/m² IV on Days 1, 8, and 15 of 28 day cycles. | 38 |
| Arm C Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 21 day cycles.
Carboplatin AUC 5 IV on Day 1 of 21 day cycles. | 23 |
| Arm C2 Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3, 8-10, and 15-17 of 21 day cycles.
Carboplatin AUC 5 IV on Day 1 of 21 day cycles. | 12 |
| Arm D-175 mg Adavosertib 175 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles.
Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles. | 6 |
| Arm D-225 mg Adavosertib 225 mg orally BID (5 doses over 3 days) on Days 1-3 of 28 day cycles.
Pegylated liposomal doxorubicin 40 mg/m² IV on Day 1 of 28 day cycles. | 6 |
| Total | 94 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Physician Decision | 0 | 1 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Arm A | Total | Arm D-225 mg | Arm D-175 mg | Arm C2 | Arm C | Arm B |
|---|---|---|---|---|---|---|---|
| Age, Categorical < 65 | 5 Participants | 59 Participants | 3 Participants | 3 Participants | 8 Participants | 14 Participants | 26 Participants |
| Age, Categorical ≥ 65 | 4 Participants | 35 Participants | 3 Participants | 3 Participants | 4 Participants | 9 Participants | 12 Participants |
| Age, Continuous | 63.0 years | 60.7 years STANDARD_DEVIATION 9.3 | 61.0 years STANDARD_DEVIATION 7.16 | 58.5 years | 58.5 years | 62.0 years | 60.0 years |
| Best overall response to most recent prior regimen Complete Response (CR) | 0 Participants | 3 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Best overall response to most recent prior regimen Non-CR/Non-PD | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Best overall response to most recent prior regimen Not Applicable | 5 Participants | 51 Participants | 1 Participants | 3 Participants | 5 Participants | 16 Participants | 21 Participants |
| Best overall response to most recent prior regimen Not Evaluable | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Best overall response to most recent prior regimen Partial Response (PR) | 0 Participants | 5 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Best overall response to most recent prior regimen Progressive Disease (PD) | 2 Participants | 23 Participants | 2 Participants | 1 Participants | 4 Participants | 5 Participants | 9 Participants |
| Best overall response to most recent prior regimen Stable Disease (SD) | 2 Participants | 10 Participants | 0 Participants | 1 Participants | 2 Participants | 1 Participants | 4 Participants |
| Body Surface Area (mean) | 1.8 m² STANDARD_DEVIATION 0.25 | 1.8 m² STANDARD_DEVIATION 0.19 | 1.7 m² STANDARD_DEVIATION 0.1 | 1.8 m² STANDARD_DEVIATION 0.18 | 1.8 m² STANDARD_DEVIATION 0.13 | 1.8 m² STANDARD_DEVIATION 0.22 | 1.8 m² STANDARD_DEVIATION 0.19 |
| Body Surface Area (median) | 1.8 m² | 1.7 m² | 1.7 m² | 1.7 m² | 1.7 m² | 1.8 m² | 1.8 m² |
| Diastolic Blood Pressure (mean) | 76.2 mmHg STANDARD_DEVIATION 10.96 | 75.8 mmHg STANDARD_DEVIATION 7.99 | 78.7 mmHg STANDARD_DEVIATION 6.02 | 73.0 mmHg STANDARD_DEVIATION 6.66 | 74.4 mmHg STANDARD_DEVIATION 8.26 | 74.8 mmHg STANDARD_DEVIATION 8.03 | 76.7 mmHg STANDARD_DEVIATION 7.74 |
| Diastolic Blood Pressure (median) | 78.0 mmHg | 76.0 mmHg | 77.5 mmHg | 74.0 mmHg | 73.5 mmHg | 75.0 mmHg | 78.0 mmHg |
| Disease setting for most recent prior regimen Adj/Neoadj in Localized disease (Stage I or II) | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Disease setting for most recent prior regimen Adjuvant | 4 Participants | 41 Participants | 1 Participants | 4 Participants | 4 Participants | 13 Participants | 15 Participants |
| Disease setting for most recent prior regimen Adjuvant in advanced disease (Stage III or IV) | 4 Participants | 39 Participants | 1 Participants | 3 Participants | 4 Participants | 13 Participants | 14 Participants |
| Disease setting for most recent prior regimen Metastatic | 5 Participants | 44 Participants | 4 Participants | 2 Participants | 6 Participants | 8 Participants | 19 Participants |
| Disease setting for most recent prior regimen Missing | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Disease setting for most recent prior regimen Neoadjuvant | 0 Participants | 9 Participants | 1 Participants | 0 Participants | 2 Participants | 2 Participants | 4 Participants |
| Disease setting for most recent prior regimen Neoadjuvant in advanced disease (Stage III or IV) | 0 Participants | 8 Participants | 1 Participants | 0 Participants | 2 Participants | 2 Participants | 3 Participants |
| Distant Metastases No | 6 Participants | 29 Participants | 1 Participants | 1 Participants | 0 Participants | 12 Participants | 9 Participants |
| Distant Metastases Yes | 3 Participants | 65 Participants | 5 Participants | 5 Participants | 12 Participants | 11 Participants | 29 Participants |
| ECOG Performance Status PS = 0 | 5 Participants | 45 Participants | 3 Participants | 1 Participants | 4 Participants | 13 Participants | 19 Participants |
| ECOG Performance Status PS = 1 | 4 Participants | 49 Participants | 3 Participants | 5 Participants | 8 Participants | 10 Participants | 19 Participants |
| ECOG Performance Status PS = 2 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| ECOG Performance Status PS = 3 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| ECOG Performance Status PS = 4 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 12 Participants | 1 Participants | 0 Participants | 2 Participants | 2 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants | 80 Participants | 5 Participants | 5 Participants | 10 Participants | 21 Participants | 31 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Histological Grade G1 - Well Differentiated | 1 Participants | 4 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 1 Participants |
| Histological Grade G2 - Moderately Differentiated | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Histological Grade G3 - Poorly Differentiated | 5 Participants | 65 Participants | 3 Participants | 5 Participants | 9 Participants | 15 Participants | 28 Participants |
| Histological Grade G4 - Undifferentiated | 0 Participants | 7 Participants | 1 Participants | 1 Participants | 0 Participants | 2 Participants | 3 Participants |
| Histological Grade GX - Grade cannot be assessed or Not Applicable | 2 Participants | 11 Participants | 2 Participants | 0 Participants | 1 Participants | 3 Participants | 3 Participants |
| Histological Grade Missing | 1 Participants | 5 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 2 Participants |
| Histology Clear Cell Epithelial Carcinoma | 0 Participants | 4 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Histology Endometrioid Carcinoma | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Histology Missing | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Histology Mixed Epithelial Carcinoma | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Histology Mucinous Epithelial Carcinoma | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Histology Serous Epithelial Carcinoma | 9 Participants | 85 Participants | 6 Participants | 4 Participants | 12 Participants | 21 Participants | 33 Participants |
| Histology Squamous Cell Epithelial Carcinoma | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Histology Transitional Cell/Brenner Carcinoma | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Histology Undifferentiated Epithelial Carcinoma | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Local or Regional Recurrence No | 4 Participants | 27 Participants | 0 Participants | 2 Participants | 3 Participants | 6 Participants | 12 Participants |
| Local or Regional Recurrence Yes | 5 Participants | 67 Participants | 6 Participants | 4 Participants | 9 Participants | 17 Participants | 26 Participants |
| Metastatic Disease No | 2 Participants | 8 Participants | 0 Participants | 1 Participants | 0 Participants | 4 Participants | 1 Participants |
| Metastatic Disease Yes | 7 Participants | 86 Participants | 6 Participants | 5 Participants | 12 Participants | 19 Participants | 37 Participants |
| Number of prior treatment regimens 0 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Number of prior treatment regimens 1 | 3 Participants | 32 Participants | 2 Participants | 3 Participants | 4 Participants | 8 Participants | 12 Participants |
| Number of prior treatment regimens 2 | 6 Participants | 43 Participants | 4 Participants | 3 Participants | 5 Participants | 9 Participants | 16 Participants |
| Number of prior treatment regimens 3 | 0 Participants | 18 Participants | 0 Participants | 0 Participants | 2 Participants | 6 Participants | 10 Participants |
| Number of prior treatment regimens >3 | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Prior Radiotherapy No | 9 Participants | 93 Participants | 6 Participants | 6 Participants | 12 Participants | 23 Participants | 37 Participants |
| Prior Radiotherapy Yes | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Prior Surgery No | 1 Participants | 6 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 3 Participants |
| Prior Surgery Yes | 8 Participants | 88 Participants | 6 Participants | 6 Participants | 11 Participants | 22 Participants | 35 Participants |
| Prior Systemic Therapy No | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Prior Systemic Therapy Yes | 9 Participants | 94 Participants | 6 Participants | 6 Participants | 12 Participants | 23 Participants | 38 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 5 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 8 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 8 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 5 Participants |
| Race (NIH/OMB) White | 7 Participants | 73 Participants | 6 Participants | 6 Participants | 10 Participants | 20 Participants | 24 Participants |
| Reason most recent prior regimen ended Completed planned treatment | 4 Participants | 38 Participants | 2 Participants | 3 Participants | 5 Participants | 10 Participants | 14 Participants |
| Reason most recent prior regimen ended Other | 0 Participants | 4 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 2 Participants |
| Reason most recent prior regimen ended Progressive Disease | 5 Participants | 46 Participants | 3 Participants | 2 Participants | 7 Participants | 10 Participants | 19 Participants |
| Reason most recent prior regimen ended Toxicity | 0 Participants | 6 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 3 Participants |
| Region of Enrollment Canada | 2 Participants | 9 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 7 Participants |
| Region of Enrollment Netherlands | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Region of Enrollment United States | 7 Participants | 84 Participants | 6 Participants | 6 Participants | 12 Participants | 23 Participants | 30 Participants |
| Sex: Female, Male Female | 9 Participants | 94 Participants | 6 Participants | 6 Participants | 12 Participants | 23 Participants | 38 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sites of Metastatic Disease Bone | 2 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Sites of Metastatic Disease Breast | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants |
| Sites of Metastatic Disease Distant Lymph Nodes | 1 Participants | 37 Participants | 1 Participants | 3 Participants | 8 Participants | 10 Participants | 14 Participants |
| Sites of Metastatic Disease Liver | 6 Participants | 31 Participants | 3 Participants | 2 Participants | 3 Participants | 4 Participants | 13 Participants |
| Sites of Metastatic Disease Local or Regional Lymph Nodes | 4 Participants | 45 Participants | 1 Participants | 1 Participants | 7 Participants | 12 Participants | 20 Participants |
| Sites of Metastatic Disease Lung | 1 Participants | 19 Participants | 2 Participants | 1 Participants | 2 Participants | 3 Participants | 10 Participants |
| Sites of Metastatic Disease Other | 4 Participants | 59 Participants | 2 Participants | 5 Participants | 9 Participants | 8 Participants | 31 Participants |
| Sites of Metastatic Disease Skin or Subcutaneous | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Stage at Initial Diagnosis IC | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Stage at Initial Diagnosis IIC | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Stage at Initial Diagnosis III | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Stage at Initial Diagnosis IIIA | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Stage at Initial Diagnosis IIIB | 0 Participants | 3 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants |
| Stage at Initial Diagnosis IIIC | 6 Participants | 44 Participants | 5 Participants | 1 Participants | 4 Participants | 14 Participants | 14 Participants |
| Stage at Initial Diagnosis IV | 3 Participants | 40 Participants | 1 Participants | 2 Participants | 8 Participants | 8 Participants | 18 Participants |
| Stage at Initial Diagnosis Missing | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Systolic Blood Pressure (mean) | 130.0 mmHg STANDARD_DEVIATION 15.23 | 126.1 mmHg STANDARD_DEVIATION 12.16 | 127.5 mmHg STANDARD_DEVIATION 9.35 | 125.2 mmHg STANDARD_DEVIATION 17.22 | 122.3 mmHg STANDARD_DEVIATION 6.4 | 127.7 mmHg STANDARD_DEVIATION 10.65 | 125.2 mmHg STANDARD_DEVIATION 13.37 |
| Systolic Blood Pressure (median) | 130.0 mmHg | 126.0 mmHg | 126.5 mmHg | 120.0 mmHg | 121.0 mmHg | 128.0 mmHg | 126.5 mmHg |
| Time from 1st positive biopsy for disease to consent for this study (mean) | 52.0 Weeks STANDARD_DEVIATION 11.83 | 68.0 Weeks STANDARD_DEVIATION 38.93 | 65.8 Weeks STANDARD_DEVIATION 20.82 | 61.4 Weeks STANDARD_DEVIATION 23.88 | 86.1 Weeks STANDARD_DEVIATION 55.67 | 62.3 Weeks STANDARD_DEVIATION 24.68 | 70.9 Weeks STANDARD_DEVIATION 46.42 |
| Time from 1st positive biopsy for disease to consent for this study (median) | 49.9 Days | 54.9 Days | 71.1 Days | 62.9 Days | 74.9 Days | 54.1 Days | 54.9 Days |
| Time from end of most recent prior systemic therapy to consent for this trial (mean) | 11.0 Weeks STANDARD_DEVIATION 9.54 | 13.1 Weeks STANDARD_DEVIATION 12.75 | 13.4 Weeks STANDARD_DEVIATION 12.08 | 12.9 Weeks STANDARD_DEVIATION 11.36 | 15.4 Weeks STANDARD_DEVIATION 15.12 | 10.5 Weeks STANDARD_DEVIATION 7.81 | 14.4 Weeks STANDARD_DEVIATION 15.45 |
| Time from end of most recent prior systemic therapy to consent for this trial (median) | 5.4 Weeks | 7.6 Weeks | 12.2 Weeks | 10.5 Weeks | 9.4 Weeks | 6.9 Weeks | 6.9 Weeks |
| Time from local/regional recurrence to consent for this study (mean) | 12.2 Weeks STANDARD_DEVIATION 14.98 | 28.6 Weeks STANDARD_DEVIATION 41.11 | 5.2 Weeks STANDARD_DEVIATION 3.61 | 39.3 Weeks STANDARD_DEVIATION 27.78 | 47.0 Weeks STANDARD_DEVIATION 57.13 | 20.6 Weeks STANDARD_DEVIATION 20.23 | 34.3 Weeks STANDARD_DEVIATION 51.2 |
| Time from local/regional recurrence to consent for this study (median) | 6.1 Weeks | 13.0 Weeks | 5.6 Weeks | 37.7 Weeks | 15.4 Weeks | 16.6 Weeks | 18.6 Weeks |
| Weight (mean) | 73.5 Kilograms STANDARD_DEVIATION 21.56 | 72.8 Kilograms STANDARD_DEVIATION 16.12 | 65.7 Kilograms STANDARD_DEVIATION 8.61 | 70.2 Kilograms STANDARD_DEVIATION 14.11 | 70.6 Kilograms STANDARD_DEVIATION 9.45 | 75.7 Kilograms STANDARD_DEVIATION 19.25 | 73.2 Kilograms STANDARD_DEVIATION 15.89 |
| Weight (median) | 69.6 Kilograms | 69.7 Kilograms | 67.8 Kilograms | 68.2 Kilograms | 67.7 Kilograms | 71.5 Kilograms | 69.6 Kilograms |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 5 / 9 | 12 / 38 | 9 / 23 | 2 / 12 | 3 / 6 | 0 / 6 |
| other Total, other adverse events | 9 / 9 | 38 / 38 | 23 / 23 | 12 / 12 | 6 / 6 | 6 / 6 |
| serious Total, serious adverse events | 4 / 9 | 17 / 38 | 12 / 23 | 8 / 12 | 2 / 6 | 1 / 6 |
Outcome results
Primary
Objective Response Rate (ORR)
Objective response rate is defined as the proportion of patients achieving a complete or partial tumour response according to RECIST v1.1 criteria.
Time frame: Throughout the duration of the study (up to 19 months)
Population: This analysis was conducted on the Full Analysis Set, comprised of all patients who received at least dose of study treatment (n = 94).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A | Objective Response Rate (ORR) | 1 Participants |
| Arm B | Objective Response Rate (ORR) | 11 Participants |
| Arm C | Objective Response Rate (ORR) | 7 Participants |
| Arm C2 | Objective Response Rate (ORR) | 8 Participants |
| Arm D-175 mg | Objective Response Rate (ORR) | 2 Participants |
| Arm D-225 mg | Objective Response Rate (ORR) | 1 Participants |
Secondary
Disease Control Rate (DCR)
The Disease Control Rate is defined as the proportion of patients achieving a complete response (CR), partial response (PR), or stable disease (SD) according to RECIST v1.1 criteria.
Time frame: Throughout the duration of the study (up to 19 months)
Population: This analysis was conducted on the Full Analysis Set, comprised of all patients who received at least dose of study treatment (n = 94).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A | Disease Control Rate (DCR) | 3 Participants |
| Arm B | Disease Control Rate (DCR) | 27 Participants |
| Arm C | Disease Control Rate (DCR) | 19 Participants |
| Arm C2 | Disease Control Rate (DCR) | 12 Participants |
| Arm D-175 mg | Disease Control Rate (DCR) | 3 Participants |
| Arm D-225 mg | Disease Control Rate (DCR) | 5 Participants |
Secondary
Duration of Response (DoR)
Duration of Response (DoR) is defined as the time from first documented tumour response until the date of documented progression or death from any cause.
Time frame: Throughout the duration of the study, approximately 19 months.
Population: Duration of Response (DoR) was calculated for all responders (N = 30)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A | Duration of Response (DoR) | 4.4 Months |
| Arm B | Duration of Response (DoR) | 12.0 Months |
| Arm C | Duration of Response (DoR) | NA Months |
| Arm C2 | Duration of Response (DoR) | 10.4 Months |
| Arm D-175 mg | Duration of Response (DoR) | NA Months |
| Arm D-225 mg | Duration of Response (DoR) | NA Months |
Secondary
Gynecologic Cancer Intergroup (GCIG) CA-125 Response
The GCIG CA-125 response is defined as the proportion of patients achieving a 50% reduction in CA-125 levels from baseline, if baseline level is ≥2 x the upper limit of normal (ULN) within 2 weeks prior to starting treatment. Response must be confirmed and maintained for at least 28 days.
Time frame: Throughout the study, approximately 4 years
Population: The CA-125 analysis set was comprised of all dosed patients with pre-treatment serum sample showing CA-125 ≥ 2 x ULN within 2 weeks before starting treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A | Gynecologic Cancer Intergroup (GCIG) CA-125 Response | 25.0 Percent |
| Arm B | Gynecologic Cancer Intergroup (GCIG) CA-125 Response | 53.6 Percent |
| Arm C | Gynecologic Cancer Intergroup (GCIG) CA-125 Response | 26.7 Percent |
| Arm C2 | Gynecologic Cancer Intergroup (GCIG) CA-125 Response | 63.6 Percent |
| Arm D-175 mg | Gynecologic Cancer Intergroup (GCIG) CA-125 Response | 25.0 Percent |
| Arm D-225 mg | Gynecologic Cancer Intergroup (GCIG) CA-125 Response | 25.0 Percent |
Secondary
Multiple Dose Adavosertib Cmax
Maximum plasma concentration of adavosertib after a multiple oral doses (Cycle 1 Day 3) in combination with IV infusion of 40 mg/m² pegylated liposomal doxorubicin.
Time frame: Pre-dose, 1 hr, 2 hr, 4 hr, 6 hr, and 8 hr
Population: The PK Analysis Set included all dosed patients who had at least one measurable plasma concentration collected post-dose which was obtained without any protocol deviation, violation, or other event which may have significantly affected the pharmacokinetics.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Arm A | Multiple Dose Adavosertib Cmax | 4135 nM | Geometric Coefficient of Variation 65.8 |
| Arm B | Multiple Dose Adavosertib Cmax | 23530 nM | Geometric Coefficient of Variation 30.15 |
Secondary
Multiple Dose Adavosertib Tmax
The time to reach maximum plasma concentration of adavosertib after multiple oral doses (Cycle 1 Day 3) in combination with IV infusion of 40 mg/m² pegylated liposomal doxorubicin.
Time frame: Pre-dose, 1 hr, 2 hr, 4 hr, 6 hr, and 8 hr
Population: The PK Analysis Set included all dosed patients who had at least one measurable plasma concentration collected post-dose which was obtained without any protocol deviation, violation, or other event which may have significantly affected the pharmacokinetics.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A | Multiple Dose Adavosertib Tmax | 3.92 hours |
| Arm B | Multiple Dose Adavosertib Tmax | 2.88 hours |
Secondary
Overall Survival (Median, 80% CI)
Overall survival (OS) was defined as the elapsed time from the date of first dose of AZD1775 until death due to any cause. Any patient not known to have died at the time of the analysis was censored based on the last recorded date on which the patient was known to be alive.
Time frame: Throughout the Study, Approximately 4 years
Population: This analysis was conducted on the Full Analysis Set, comprised of all patients who received at least dose of study treatment (n = 94).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A | Overall Survival (Median, 80% CI) | 16.0 Months |
| Arm B | Overall Survival (Median, 80% CI) | NA Months |
| Arm C | Overall Survival (Median, 80% CI) | 8.9 Months |
| Arm C2 | Overall Survival (Median, 80% CI) | 19.2 Months |
| Arm D-175 mg | Overall Survival (Median, 80% CI) | 3.8 Months |
| Arm D-225 mg | Overall Survival (Median, 80% CI) | NA Months |
Secondary
Overall Survival (Median, 95% CI)
Overall survival (OS) was defined as the elapsed time from the date of first dose of AZD1775 until death due to any cause. Any patient not known to have died at the time of the analysis was censored based on the last recorded date on which the patient was known to be alive.
Time frame: Throughout the Study, Approximately 4 years
Population: This analysis was conducted on the Full Analysis Set, comprised of all patients who received at least dose of study treatment (n = 94).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A | Overall Survival (Median, 95% CI) | 16.0 Months |
| Arm B | Overall Survival (Median, 95% CI) | NA Months |
| Arm C | Overall Survival (Median, 95% CI) | 8.9 Months |
| Arm C2 | Overall Survival (Median, 95% CI) | 19.2 Months |
| Arm D-175 mg | Overall Survival (Median, 95% CI) | 6.2 Months |
| Arm D-225 mg | Overall Survival (Median, 95% CI) | NA Months |
Secondary
Progression Free Survival (Median, 80% CI)
Progression-free survival (PFS) was defined as the elapsed time from date of first dose of AZD1775 until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdrew from therapy or received another anti-cancer therapy prior to progression. Patients who had not progressed or died at the time of analysis were censored at the time of the latest date of assessment from their last evaluable RECIST assessment. Progression-free survival was derived based on scan/assessment dates, not visit dates.
Time frame: Throughout the Study, Approximately 4 years
Population: This analysis was conducted on the Full Analysis Set, comprised of all patients who received at least dose of study treatment (n = 94).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A | Progression Free Survival (Median, 80% CI) | 1.7 Months |
| Arm B | Progression Free Survival (Median, 80% CI) | 5.5 Months |
| Arm C | Progression Free Survival (Median, 80% CI) | 4.2 Months |
| Arm C2 | Progression Free Survival (Median, 80% CI) | 12.0 Months |
| Arm D-175 mg | Progression Free Survival (Median, 80% CI) | 2.7 Months |
| Arm D-225 mg | Progression Free Survival (Median, 80% CI) | NA Months |
Secondary
Progression Free Survival (Median, 95% CI)
Progression-free survival (PFS) was defined as the elapsed time from date of first dose of AZD1775 until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdrew from therapy or received another anti-cancer therapy prior to progression. Patients who had not progressed or died at the time of analysis were censored at the time of the latest date of assessment from their last evaluable RECIST assessment. Progression-free survival was derived based on scan/assessment dates, not visit dates.
Time frame: Throughout the Study, Approximately 4 years
Population: This analysis was conducted on the Full Analysis Set, comprised of all patients who received at least dose of study treatment (n = 94).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A | Progression Free Survival (Median, 95% CI) | 1.7 Months |
| Arm B | Progression Free Survival (Median, 95% CI) | 5.5 Months |
| Arm C | Progression Free Survival (Median, 95% CI) | 4.2 Months |
| Arm C2 | Progression Free Survival (Median, 95% CI) | 12.0 Months |
| Arm D-175 mg | Progression Free Survival (Median, 95% CI) | 2.7 Months |
| Arm D-225 mg | Progression Free Survival (Median, 95% CI) | NA Months |
Secondary
Serious Adverse Events
The number of patients experiencing at least one serious adverse event (SAE).
Time frame: Throughout the duration of the study (up to 19 months)
Population: This analysis was conducted on the Full Analysis Set, comprised of all patients who received at least dose of study treatment (n = 94).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm A | Serious Adverse Events | Pts. with ≥ one serious TEAE related to AZD1775. | 0 Participants |
| Arm A | Serious Adverse Events | Pts. with ≥ one serious TEAE related to Chemo. | 0 Participants |
| Arm B | Serious Adverse Events | Pts. with ≥ one serious TEAE related to AZD1775. | 8 Participants |
| Arm B | Serious Adverse Events | Pts. with ≥ one serious TEAE related to Chemo. | 8 Participants |
| Arm C | Serious Adverse Events | Pts. with ≥ one serious TEAE related to AZD1775. | 9 Participants |
| Arm C | Serious Adverse Events | Pts. with ≥ one serious TEAE related to Chemo. | 9 Participants |
| Arm C2 | Serious Adverse Events | Pts. with ≥ one serious TEAE related to AZD1775. | 7 Participants |
| Arm C2 | Serious Adverse Events | Pts. with ≥ one serious TEAE related to Chemo. | 7 Participants |
| Arm D-175 mg | Serious Adverse Events | Pts. with ≥ one serious TEAE related to AZD1775. | 1 Participants |
| Arm D-175 mg | Serious Adverse Events | Pts. with ≥ one serious TEAE related to Chemo. | 1 Participants |
| Arm D-225 mg | Serious Adverse Events | Pts. with ≥ one serious TEAE related to AZD1775. | 1 Participants |
| Arm D-225 mg | Serious Adverse Events | Pts. with ≥ one serious TEAE related to Chemo. | 1 Participants |
Secondary
Serious Adverse Events Leading to Death
The number of patients experiencing at least one serious adverse event (SAE) leading to death.
Time frame: Throughout the duration of the study (up to 19 months)
Population: This analysis was conducted on the Full Analysis Set, comprised of all patients who received at least dose of study treatment (n = 94).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm A | Serious Adverse Events Leading to Death | No. with STEAE related to AZD1775 leading to death | 0 Participants |
| Arm A | Serious Adverse Events Leading to Death | No. with STEAE related to chemo leading to death | 0 Participants |
| Arm B | Serious Adverse Events Leading to Death | No. with STEAE related to AZD1775 leading to death | 1 Participants |
| Arm B | Serious Adverse Events Leading to Death | No. with STEAE related to chemo leading to death | 1 Participants |
| Arm C | Serious Adverse Events Leading to Death | No. with STEAE related to AZD1775 leading to death | 0 Participants |
| Arm C | Serious Adverse Events Leading to Death | No. with STEAE related to chemo leading to death | 0 Participants |
| Arm C2 | Serious Adverse Events Leading to Death | No. with STEAE related to AZD1775 leading to death | 0 Participants |
| Arm C2 | Serious Adverse Events Leading to Death | No. with STEAE related to chemo leading to death | 0 Participants |
| Arm D-175 mg | Serious Adverse Events Leading to Death | No. with STEAE related to AZD1775 leading to death | 0 Participants |
| Arm D-175 mg | Serious Adverse Events Leading to Death | No. with STEAE related to chemo leading to death | 0 Participants |
| Arm D-225 mg | Serious Adverse Events Leading to Death | No. with STEAE related to AZD1775 leading to death | 0 Participants |
| Arm D-225 mg | Serious Adverse Events Leading to Death | No. with STEAE related to chemo leading to death | 0 Participants |
Secondary
Single Dose Adavosertib Cmax
Maximum plasma concentration of adavosertib after a single oral dose (Cycle 1 Day 1) in combination with IV infusion of commonly used chemotherapy agents, including gemcitabine, paclitaxel, and carboplatin.
Time frame: Pre-dose, 0.5 hr, 1 hr, 2 hr, 4 hr, 6 hr, and 8 hr
Population: The PK Analysis Set included all dosed patients who had at least one measurable plasma concentration collected post-dose which was obtained without any protocol deviation, violation, or other event which may have significantly affected the pharmacokinetics.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Arm A | Single Dose Adavosertib Cmax | 477.4 nM | Geometric Coefficient of Variation 3.776 |
| Arm B | Single Dose Adavosertib Cmax | 571.1 nM | Geometric Coefficient of Variation 29.79 |
| Arm C | Single Dose Adavosertib Cmax | 533.8 nM | Geometric Coefficient of Variation 37.29 |
| Arm C2 | Single Dose Adavosertib Cmax | 556.6 nM | Geometric Coefficient of Variation 56.39 |
Secondary
Single Dose Adavosertib Tmax
The time to reach maximum plasma concentration of adavosertib after a single oral dose (Cycle 1 Day 1) in combination with IV infusion of commonly used chemotherapy agents, including gemcitabine, paclitaxel, and carboplatin.
Time frame: Pre-dose, 0.5 hr, 1 hr, 2 hr, 4 hr, 6 hr, and 8 hr
Population: The PK Analysis Set included all dosed patients who had at least one measurable plasma concentration collected post-dose which was obtained without any protocol deviation, violation, or other event which may have significantly affected the pharmacokinetics.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A | Single Dose Adavosertib Tmax | 2.00 hours |
| Arm B | Single Dose Adavosertib Tmax | 2.02 hours |
| Arm C | Single Dose Adavosertib Tmax | 4.08 hours |
| Arm C2 | Single Dose Adavosertib Tmax | 3.15 hours |
Secondary
The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) by Maximum CTCAE Grade.
The number of patients experiencing at least one treatment-related adverse event (TEAE) by maximum CTCAE grade. Severity Grade 1 = Mild; Severity Grade 2 = Moderate; Severity Grade 3 = Severe; Severity Grade 4 = Life Threatening; Severity Grade 5 = Fatal
Time frame: Throughout the duration of the study (up to 19 months)
Population: This analysis was conducted on the Full Analysis Set, comprised of all patients who received at least dose of study treatment (n = 94).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm A | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) by Maximum CTCAE Grade. | Number of patients with ≥1 TEAE of max Grade 4 | 6 Participants |
| Arm A | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) by Maximum CTCAE Grade. | Number of patients with ≥1 TEAE of max Grade 2 | 1 Participants |
| Arm A | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) by Maximum CTCAE Grade. | Number of patients with ≥1 TEAE of max Grade 1 | 0 Participants |
| Arm A | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) by Maximum CTCAE Grade. | Number of patients with ≥1 TEAE of max Grade 5 | 0 Participants |
| Arm A | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) by Maximum CTCAE Grade. | Number of patients with ≥1 TEAE of max Grade 3 | 2 Participants |
| Arm B | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) by Maximum CTCAE Grade. | Number of patients with ≥1 TEAE of max Grade 2 | 1 Participants |
| Arm B | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) by Maximum CTCAE Grade. | Number of patients with ≥1 TEAE of max Grade 4 | 15 Participants |
| Arm B | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) by Maximum CTCAE Grade. | Number of patients with ≥1 TEAE of max Grade 1 | 2 Participants |
| Arm B | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) by Maximum CTCAE Grade. | Number of patients with ≥1 TEAE of max Grade 5 | 1 Participants |
| Arm B | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) by Maximum CTCAE Grade. | Number of patients with ≥1 TEAE of max Grade 3 | 19 Participants |
| Arm C | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) by Maximum CTCAE Grade. | Number of patients with ≥1 TEAE of max Grade 2 | 5 Participants |
| Arm C | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) by Maximum CTCAE Grade. | Number of patients with ≥1 TEAE of max Grade 4 | 8 Participants |
| Arm C | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) by Maximum CTCAE Grade. | Number of patients with ≥1 TEAE of max Grade 5 | 0 Participants |
| Arm C | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) by Maximum CTCAE Grade. | Number of patients with ≥1 TEAE of max Grade 3 | 10 Participants |
| Arm C | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) by Maximum CTCAE Grade. | Number of patients with ≥1 TEAE of max Grade 1 | 0 Participants |
| Arm C2 | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) by Maximum CTCAE Grade. | Number of patients with ≥1 TEAE of max Grade 3 | 4 Participants |
| Arm C2 | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) by Maximum CTCAE Grade. | Number of patients with ≥1 TEAE of max Grade 1 | 0 Participants |
| Arm C2 | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) by Maximum CTCAE Grade. | Number of patients with ≥1 TEAE of max Grade 2 | 0 Participants |
| Arm C2 | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) by Maximum CTCAE Grade. | Number of patients with ≥1 TEAE of max Grade 4 | 8 Participants |
| Arm C2 | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) by Maximum CTCAE Grade. | Number of patients with ≥1 TEAE of max Grade 5 | 0 Participants |
| Arm D-175 mg | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) by Maximum CTCAE Grade. | Number of patients with ≥1 TEAE of max Grade 4 | 0 Participants |
| Arm D-175 mg | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) by Maximum CTCAE Grade. | Number of patients with ≥1 TEAE of max Grade 1 | 0 Participants |
| Arm D-175 mg | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) by Maximum CTCAE Grade. | Number of patients with ≥1 TEAE of max Grade 5 | 0 Participants |
| Arm D-175 mg | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) by Maximum CTCAE Grade. | Number of patients with ≥1 TEAE of max Grade 2 | 3 Participants |
| Arm D-175 mg | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) by Maximum CTCAE Grade. | Number of patients with ≥1 TEAE of max Grade 3 | 3 Participants |
| Arm D-225 mg | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) by Maximum CTCAE Grade. | Number of patients with ≥1 TEAE of max Grade 1 | 0 Participants |
| Arm D-225 mg | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) by Maximum CTCAE Grade. | Number of patients with ≥1 TEAE of max Grade 4 | 2 Participants |
| Arm D-225 mg | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) by Maximum CTCAE Grade. | Number of patients with ≥1 TEAE of max Grade 2 | 4 Participants |
| Arm D-225 mg | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) by Maximum CTCAE Grade. | Number of patients with ≥1 TEAE of max Grade 5 | 0 Participants |
| Arm D-225 mg | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) by Maximum CTCAE Grade. | Number of patients with ≥1 TEAE of max Grade 3 | 0 Participants |
Secondary
The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Adavosertib by Maximum CTCAE Grade
The number and proportion of patients experiencing at least one treatment-related adverse event (TEAE) related to adavosertib by maximum CTCAE grade Severity Grade 1 = Mild; Severity Grade 2 = Moderate; Severity Grade 3 = Severe; Severity Grade 4 = Life Threatening; Severity Grade 5 = Fatal
Time frame: Throughout the duration of the study (up to 19 months)
Population: This analysis was conducted on the Full Analysis Set, comprised of all patients who received at least dose of study treatment (n = 94).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm A | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Adavosertib by Maximum CTCAE Grade | Number of patients with ≥1 TEAE of max Grade 4 | 5 Participants |
| Arm A | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Adavosertib by Maximum CTCAE Grade | Number of patients with ≥1 TEAE of max Grade 2 | 1 Participants |
| Arm A | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Adavosertib by Maximum CTCAE Grade | Number of patients with ≥1 TEAE of max Grade 1 | 0 Participants |
| Arm A | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Adavosertib by Maximum CTCAE Grade | Number of patients with ≥1 TEAE of max Grade 5 | 0 Participants |
| Arm A | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Adavosertib by Maximum CTCAE Grade | Number of patients with ≥1 TEAE of max Grade 3 | 3 Participants |
| Arm B | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Adavosertib by Maximum CTCAE Grade | Number of patients with ≥1 TEAE of max Grade 2 | 4 Participants |
| Arm B | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Adavosertib by Maximum CTCAE Grade | Number of patients with ≥1 TEAE of max Grade 4 | 14 Participants |
| Arm B | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Adavosertib by Maximum CTCAE Grade | Number of patients with ≥1 TEAE of max Grade 1 | 3 Participants |
| Arm B | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Adavosertib by Maximum CTCAE Grade | Number of patients with ≥1 TEAE of max Grade 5 | 1 Participants |
| Arm B | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Adavosertib by Maximum CTCAE Grade | Number of patients with ≥1 TEAE of max Grade 3 | 16 Participants |
| Arm C | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Adavosertib by Maximum CTCAE Grade | Number of patients with ≥1 TEAE of max Grade 2 | 5 Participants |
| Arm C | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Adavosertib by Maximum CTCAE Grade | Number of patients with ≥1 TEAE of max Grade 4 | 8 Participants |
| Arm C | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Adavosertib by Maximum CTCAE Grade | Number of patients with ≥1 TEAE of max Grade 5 | 0 Participants |
| Arm C | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Adavosertib by Maximum CTCAE Grade | Number of patients with ≥1 TEAE of max Grade 3 | 7 Participants |
| Arm C | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Adavosertib by Maximum CTCAE Grade | Number of patients with ≥1 TEAE of max Grade 1 | 2 Participants |
| Arm C2 | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Adavosertib by Maximum CTCAE Grade | Number of patients with ≥1 TEAE of max Grade 3 | 4 Participants |
| Arm C2 | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Adavosertib by Maximum CTCAE Grade | Number of patients with ≥1 TEAE of max Grade 1 | 0 Participants |
| Arm C2 | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Adavosertib by Maximum CTCAE Grade | Number of patients with ≥1 TEAE of max Grade 2 | 0 Participants |
| Arm C2 | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Adavosertib by Maximum CTCAE Grade | Number of patients with ≥1 TEAE of max Grade 4 | 8 Participants |
| Arm C2 | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Adavosertib by Maximum CTCAE Grade | Number of patients with ≥1 TEAE of max Grade 5 | 0 Participants |
| Arm D-175 mg | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Adavosertib by Maximum CTCAE Grade | Number of patients with ≥1 TEAE of max Grade 4 | 0 Participants |
| Arm D-175 mg | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Adavosertib by Maximum CTCAE Grade | Number of patients with ≥1 TEAE of max Grade 1 | 0 Participants |
| Arm D-175 mg | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Adavosertib by Maximum CTCAE Grade | Number of patients with ≥1 TEAE of max Grade 5 | 0 Participants |
| Arm D-175 mg | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Adavosertib by Maximum CTCAE Grade | Number of patients with ≥1 TEAE of max Grade 2 | 5 Participants |
| Arm D-175 mg | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Adavosertib by Maximum CTCAE Grade | Number of patients with ≥1 TEAE of max Grade 3 | 1 Participants |
| Arm D-225 mg | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Adavosertib by Maximum CTCAE Grade | Number of patients with ≥1 TEAE of max Grade 1 | 0 Participants |
| Arm D-225 mg | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Adavosertib by Maximum CTCAE Grade | Number of patients with ≥1 TEAE of max Grade 4 | 2 Participants |
| Arm D-225 mg | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Adavosertib by Maximum CTCAE Grade | Number of patients with ≥1 TEAE of max Grade 2 | 4 Participants |
| Arm D-225 mg | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Adavosertib by Maximum CTCAE Grade | Number of patients with ≥1 TEAE of max Grade 5 | 0 Participants |
| Arm D-225 mg | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Adavosertib by Maximum CTCAE Grade | Number of patients with ≥1 TEAE of max Grade 3 | 0 Participants |
Secondary
The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Chemotherapy by Maximum CTCAE Grade
The number of patients experiencing at least one treatment-related adverse event (TEAE) related to chemotherapy by maximum CTCAE grade. Severity Grade 1 = Mild; Severity Grade 2 = Moderate; Severity Grade 3 = Severe; Severity Grade 4 = Life Threatening; Severity Grade 5 = Fatal
Time frame: Throughout the duration of the study (up to 19 months)
Population: This analysis was conducted on the Full Analysis Set, comprised of all patients who received at least dose of study treatment (n = 94).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm A | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Chemotherapy by Maximum CTCAE Grade | Number of patients with ≥1 TEAE of max Grade 4 | 5 Participants |
| Arm A | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Chemotherapy by Maximum CTCAE Grade | Number of patients with ≥1 TEAE of max Grade 2 | 1 Participants |
| Arm A | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Chemotherapy by Maximum CTCAE Grade | Number of patients with ≥1 TEAE of max Grade 1 | 0 Participants |
| Arm A | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Chemotherapy by Maximum CTCAE Grade | Number of patients with ≥1 TEAE of max Grade 5 | 0 Participants |
| Arm A | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Chemotherapy by Maximum CTCAE Grade | Number of patients with ≥1 TEAE of max Grade 3 | 3 Participants |
| Arm B | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Chemotherapy by Maximum CTCAE Grade | Number of patients with ≥1 TEAE of max Grade 2 | 5 Participants |
| Arm B | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Chemotherapy by Maximum CTCAE Grade | Number of patients with ≥1 TEAE of max Grade 4 | 15 Participants |
| Arm B | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Chemotherapy by Maximum CTCAE Grade | Number of patients with ≥1 TEAE of max Grade 1 | 4 Participants |
| Arm B | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Chemotherapy by Maximum CTCAE Grade | Number of patients with ≥1 TEAE of max Grade 5 | 1 Participants |
| Arm B | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Chemotherapy by Maximum CTCAE Grade | Number of patients with ≥1 TEAE of max Grade 3 | 13 Participants |
| Arm C | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Chemotherapy by Maximum CTCAE Grade | Number of patients with ≥1 TEAE of max Grade 2 | 6 Participants |
| Arm C | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Chemotherapy by Maximum CTCAE Grade | Number of patients with ≥1 TEAE of max Grade 4 | 8 Participants |
| Arm C | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Chemotherapy by Maximum CTCAE Grade | Number of patients with ≥1 TEAE of max Grade 5 | 0 Participants |
| Arm C | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Chemotherapy by Maximum CTCAE Grade | Number of patients with ≥1 TEAE of max Grade 3 | 8 Participants |
| Arm C | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Chemotherapy by Maximum CTCAE Grade | Number of patients with ≥1 TEAE of max Grade 1 | 0 Participants |
| Arm C2 | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Chemotherapy by Maximum CTCAE Grade | Number of patients with ≥1 TEAE of max Grade 3 | 4 Participants |
| Arm C2 | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Chemotherapy by Maximum CTCAE Grade | Number of patients with ≥1 TEAE of max Grade 1 | 0 Participants |
| Arm C2 | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Chemotherapy by Maximum CTCAE Grade | Number of patients with ≥1 TEAE of max Grade 2 | 0 Participants |
| Arm C2 | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Chemotherapy by Maximum CTCAE Grade | Number of patients with ≥1 TEAE of max Grade 4 | 8 Participants |
| Arm C2 | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Chemotherapy by Maximum CTCAE Grade | Number of patients with ≥1 TEAE of max Grade 5 | 0 Participants |
| Arm D-175 mg | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Chemotherapy by Maximum CTCAE Grade | Number of patients with ≥1 TEAE of max Grade 4 | 0 Participants |
| Arm D-175 mg | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Chemotherapy by Maximum CTCAE Grade | Number of patients with ≥1 TEAE of max Grade 1 | 0 Participants |
| Arm D-175 mg | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Chemotherapy by Maximum CTCAE Grade | Number of patients with ≥1 TEAE of max Grade 5 | 0 Participants |
| Arm D-175 mg | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Chemotherapy by Maximum CTCAE Grade | Number of patients with ≥1 TEAE of max Grade 2 | 5 Participants |
| Arm D-175 mg | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Chemotherapy by Maximum CTCAE Grade | Number of patients with ≥1 TEAE of max Grade 3 | 1 Participants |
| Arm D-225 mg | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Chemotherapy by Maximum CTCAE Grade | Number of patients with ≥1 TEAE of max Grade 1 | 0 Participants |
| Arm D-225 mg | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Chemotherapy by Maximum CTCAE Grade | Number of patients with ≥1 TEAE of max Grade 4 | 2 Participants |
| Arm D-225 mg | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Chemotherapy by Maximum CTCAE Grade | Number of patients with ≥1 TEAE of max Grade 2 | 4 Participants |
| Arm D-225 mg | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Chemotherapy by Maximum CTCAE Grade | Number of patients with ≥1 TEAE of max Grade 5 | 0 Participants |
| Arm D-225 mg | The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Chemotherapy by Maximum CTCAE Grade | Number of patients with ≥1 TEAE of max Grade 3 | 0 Participants |
Secondary
Treatment-Related Adverse Events Related to Adavosertib Leading to Dose Reduction
The number of patients experiencing at least one treatment-related adverse event related to adavosertib leading to dose reduction.
Time frame: Throughout the duration of the study (up to 19 months)
Population: This analysis was conducted on the Full Analysis Set, comprised of all patients who received at least dose of study treatment (n = 94).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A | Treatment-Related Adverse Events Related to Adavosertib Leading to Dose Reduction | 2 Participants |
| Arm B | Treatment-Related Adverse Events Related to Adavosertib Leading to Dose Reduction | 18 Participants |
| Arm C | Treatment-Related Adverse Events Related to Adavosertib Leading to Dose Reduction | 5 Participants |
| Arm C2 | Treatment-Related Adverse Events Related to Adavosertib Leading to Dose Reduction | 11 Participants |
| Arm D-175 mg | Treatment-Related Adverse Events Related to Adavosertib Leading to Dose Reduction | 0 Participants |
| Arm D-225 mg | Treatment-Related Adverse Events Related to Adavosertib Leading to Dose Reduction | 0 Participants |
Secondary
Treatment-Related Adverse Events Related to Adavosertib Leading to Treatment Discontinuation
The number of patients experiencing at least one treatment-related adverse event related to adavosertib leading to treatment discontinuation.
Time frame: Throughout the duration of the study (up to 19 months)
Population: This analysis was conducted on the Full Analysis Set, comprised of all patients who received at least dose of study treatment (n = 94).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A | Treatment-Related Adverse Events Related to Adavosertib Leading to Treatment Discontinuation | 0 Participants |
| Arm B | Treatment-Related Adverse Events Related to Adavosertib Leading to Treatment Discontinuation | 6 Participants |
| Arm C | Treatment-Related Adverse Events Related to Adavosertib Leading to Treatment Discontinuation | 5 Participants |
| Arm C2 | Treatment-Related Adverse Events Related to Adavosertib Leading to Treatment Discontinuation | 1 Participants |
| Arm D-175 mg | Treatment-Related Adverse Events Related to Adavosertib Leading to Treatment Discontinuation | 0 Participants |
| Arm D-225 mg | Treatment-Related Adverse Events Related to Adavosertib Leading to Treatment Discontinuation | 0 Participants |
Secondary
Treatment-Related Adverse Events Related to Adavosertib Leading to Treatment Interruption
The number of patients experiencing at least one treatment-related adverse event related to adavosertib leading to treatment interruption.
Time frame: Throughout the duration of the study (up to 19 months)
Population: This analysis was conducted on the Full Analysis Set, comprised of all patients who received at least dose of study treatment (n = 94).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A | Treatment-Related Adverse Events Related to Adavosertib Leading to Treatment Interruption | 8 Participants |
| Arm B | Treatment-Related Adverse Events Related to Adavosertib Leading to Treatment Interruption | 30 Participants |
| Arm C | Treatment-Related Adverse Events Related to Adavosertib Leading to Treatment Interruption | 10 Participants |
| Arm C2 | Treatment-Related Adverse Events Related to Adavosertib Leading to Treatment Interruption | 11 Participants |
| Arm D-175 mg | Treatment-Related Adverse Events Related to Adavosertib Leading to Treatment Interruption | 0 Participants |
| Arm D-225 mg | Treatment-Related Adverse Events Related to Adavosertib Leading to Treatment Interruption | 1 Participants |
Secondary
Treatment-Related Adverse Events Related to Chemotherapy Leading to Dose Reduction
The number of patients experiencing at least one treatment-related adverse event related to chemotherapy leading to dose reduction.
Time frame: Throughout the duration of the study (up to 19 months)
Population: This analysis was conducted on the Full Analysis Set, comprised of all patients who received at least dose of study treatment (n = 94).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A | Treatment-Related Adverse Events Related to Chemotherapy Leading to Dose Reduction | 6 Participants |
| Arm B | Treatment-Related Adverse Events Related to Chemotherapy Leading to Dose Reduction | 19 Participants |
| Arm C | Treatment-Related Adverse Events Related to Chemotherapy Leading to Dose Reduction | 8 Participants |
| Arm C2 | Treatment-Related Adverse Events Related to Chemotherapy Leading to Dose Reduction | 11 Participants |
| Arm D-175 mg | Treatment-Related Adverse Events Related to Chemotherapy Leading to Dose Reduction | 0 Participants |
| Arm D-225 mg | Treatment-Related Adverse Events Related to Chemotherapy Leading to Dose Reduction | 0 Participants |
Secondary
Treatment-Related Adverse Events Related to Chemotherapy Leading to Treatment Discontinuation
The number of patients experiencing at least one treatment-related adverse event related to chemotherapy leading to treatment discontinuation.
Time frame: Throughout the duration of the study (up to 19 months)
Population: This analysis was conducted on the Full Analysis Set, comprised of all patients who received at least dose of study treatment (n = 94).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A | Treatment-Related Adverse Events Related to Chemotherapy Leading to Treatment Discontinuation | 0 Participants |
| Arm B | Treatment-Related Adverse Events Related to Chemotherapy Leading to Treatment Discontinuation | 6 Participants |
| Arm C | Treatment-Related Adverse Events Related to Chemotherapy Leading to Treatment Discontinuation | 5 Participants |
| Arm C2 | Treatment-Related Adverse Events Related to Chemotherapy Leading to Treatment Discontinuation | 1 Participants |
| Arm D-175 mg | Treatment-Related Adverse Events Related to Chemotherapy Leading to Treatment Discontinuation | 0 Participants |
| Arm D-225 mg | Treatment-Related Adverse Events Related to Chemotherapy Leading to Treatment Discontinuation | 0 Participants |
Secondary
Treatment-Related Adverse Events Related to Chemotherapy Leading to Treatment Interruption
The number of patients experiencing at least one treatment-related adverse event related to chemotherapy leading to treatment interruption.
Time frame: Throughout the duration of the study (up to 19 months)
Population: This analysis was conducted on the Full Analysis Set, comprised of all patients who received at least dose of study treatment (n = 94).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A | Treatment-Related Adverse Events Related to Chemotherapy Leading to Treatment Interruption | 8 Participants |
| Arm B | Treatment-Related Adverse Events Related to Chemotherapy Leading to Treatment Interruption | 28 Participants |
| Arm C | Treatment-Related Adverse Events Related to Chemotherapy Leading to Treatment Interruption | 12 Participants |
| Arm C2 | Treatment-Related Adverse Events Related to Chemotherapy Leading to Treatment Interruption | 9 Participants |
| Arm D-175 mg | Treatment-Related Adverse Events Related to Chemotherapy Leading to Treatment Interruption | 0 Participants |
| Arm D-225 mg | Treatment-Related Adverse Events Related to Chemotherapy Leading to Treatment Interruption | 1 Participants |