Absorption, Metabolism, Excretion and Pharmacokinetics of a Single Dose [14C]AZD2014 Followed by a Multiple Dose Phase

A Phase I, Open-Label, Non-randomised, Single Centre Study of the Absorption, Metabolism, Excretion and Pharmacokinetics of AZD2014 After a Single Oral Dose of [14C]AZD2014, Followed by Multiple Doses of AZD2014 Either As Monotherapy or In Combination With Either Fulvestrant or Paclitaxel in Patients With Advanced Solid Malignancies

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02640755

Acronym

14C

Enrollment

Registered

2015-12-29

Start date

2016-01-28

Completion date

2017-07-06

Last updated

2019-04-22

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Solid Malignancies

Keywords

Radiolabelled

Brief summary

This Phase 1, open label, single centre, non-randomised study in patients with advanced solid malignancies consists of two parts: 1. Single Dose Period - will characterise the absorption, metabolism, excretion and pharmacokinetics of a single oral dose of \[14C\]AZD2014 from the body 2. Multiple Dose Period - will further assess the safety and tolerability and anti-tumour activity of multiple doses of AZD2014 when given as a monotherapy or given in combination with paclitaxel or fulvestrant.

Detailed description

This is a Phase I, open label, single centre, non-randomised study in patients with advanced solid malignancies that is refractory or resistant to standard treatment or where no suitable effective standard treatment exists or for whom paclitaxel or fulvestrant are appropriate treatment choices. The study will be divided in two parts: 1. Single Dose Period - will enrol up to 6 evaluable patients to characterise the absorption, metabolism, excretion and pharmacokinetics of a single radiolabelled \[14C\] oral dose of 125mg AZD2014 via residential intensive PK sampling over 8 days. An evaluable patient is defined as patient who does not vomit within 2 hours post dose and who has completed the scheduled PK sampling. 2. Multiple Dose Period - patients who have completed the Single Dose Period may continue to receive treatment as outpatients. Patients will be allocated to different treatment regimes as decided between Investigator and patient on a risk / benefit basis. From Day 1, Cycle 1, non-radiolabelled AZD2014 treatment will be administered as oral tablets to patients, either as: i. 50mg BD monotherapy ii. 125mg BD taken on first 2 days of treatment each week in combination with 500mg intramuscular fulvestrant on Day 1, Cycle 1, Day 15, Cycle 1; Day 1, Cycle 2, then Day 1 of each monthly cycle thereafter iii. 50mg BD taken on first 3 days of treatment each week for 6 weeks in combination with a single weekly paclitaxel infusion (80mg/m2 ) followed by a one week break from treatment where no AZD2014 or paclitaxel will be given. This 7 week schedule composes one cycle of treatment. Patients will be given up to 6 cycles of paclitaxel, although additional cycles of paclitaxel may be given if deemed appropriate by the Investigator. Radiolabelled AZD2014 will be administered to fasted patients (i.e. no food 2 hours before and 1 hour after each dose). Non-radiolabelled AZD2014 will be administered either under fasted or non-fasted conditions. The safety and tolerability and anti-tumour activity of AZD2014 and combination with paclitaxel or fulvestrant will be evaluated in all enrolled patients respectively using conventional safety parameters, AEs/SAEs and RECIST 1.1.

Interventions

DRUG[14C]AZD2014

Radiolabelled dual TORC1/TORC2 inhibitor

DRUGMultiple dose AZD2014

Dual TORC1/TORC2 inhibitor

DRUGFulvestrant

Hormonal Agent

DRUGPaclitaxel

Taxane

Study design

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

OTHER

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 130 Years

Healthy volunteers

Inclusion criteria

* Provision of signed, written & dated informed consent prior to any study specific procedures. * Male or female patients aged at least 18 years. * Have a body mass index (BMI) ≥18 kg/m2 and ≤35 kg/m2 & weigh at least 50 kg. * Histological or cytological confirmation of a solid malignant tumour that is refractory or resistant to standard therapies or for which no suitable effective standard therapies exist. SqNSCLC patients are excluded from the 50mg BD AZD2014 in combination with paclitaxel cohort. * For patients intending to enter combination therapy with fulvestrant or paclitaxel, this should be deemed as an appropriate treatment option by Investigator. * Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 with no deterioration over previous 2 weeks & minimum life expectancy of 12 weeks. * At least one lesion (measurable and/or non-measurable but evaluable) that can be accurately assessed at baseline by computerised tomography (CT) magnetic resonance imaging (MRI) or plain X-ray & is suitable for repeated assessment * Able & willing to stay in hospital for approximately 9 days * Females should be using adequate contraceptive measures, should not be breast feeding & must have negative pregnancy test prior to start of dosing if of childbearing potential or must have evidence of non-childbearing potential * Male patients should be surgically sterile or willing to use barrier contraception ie, condoms and spermicide &refrain from donating sperm from start of dosing until 16 weeks after discontinuing of study treatment. * Regular bowel movements (ie, on average production of at least 1 stool per day)

Exclusion criteria

* Involvement in planning and/or conduct of the study * Previous enrolment in present study * Another study with an investigational product in last 28 days * Chemotherapy, biological therapy, radiation therapy, androgens, thalidomide, immunotherapy, other anticancer agents & any investigational agents within 21 days of starting treatment (not including palliative radiotherapy at focal sites), or corticosteroids within 14 days * Major surgery within 4 weeks, or minor surgery within 14 days * Exposure to strong and moderate inhibitors or inducers of cytochrome P450 (CYP) 3A4/5, P-glycoprotein (Pgp) (multidrug resistance gene \[MDR1\]), and breast cancer resistance protein (BCRP), if taken within stated washout periods * Exposure to specific substrates of the drug organic anion-transporting polypeptide (OATP)1B1, OATP1B3, organic anion transporting polypeptide (OCT)1 and OCT2 within appropriate washout period * Any haemopoietic growth factors (eg, filgrastim \[granulocyte colony-stimulating factor; G-CSF\], sargramostim \[granulocyte-macrophage colony-stimulating factor; GM-CSF\]) within 14 days prior to receiving study treatment * Previous treatment with AZD2014 or AZD8055 * Patients who have received fulvestrant within 3 months * With exception of alopecia, any unresolved toxicities chemotherapy/radiotherapy should be no greater than CTCAE grade 1 * Participated in another absorption, distribution, metabolism and excretion study within 1 year * Spinal cord compression and/or brain metastases unless asymptomatic or treated & stable off steroids for at least 4 weeks * Severe or uncontrolled systemic diseases (eg, severe hepatic impairment, interstitial lung disease \[bilateral, diffuse, parenchymal lung disease\]), or current unstable or uncompensated respiratory or cardiac conditions, or uncontrolled hypertension, active bleeding diatheses or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV). * Recent history of drug abuse or alcohol abuse * Patients who have undergone any of the following procedures or experienced conditions currently or in preceding 12 months: * Coronary artery bypass graft * Angioplasty * Vascular stent * Myocardial infarction * Angina pectoris * Congestive heart failure New York Heart Association Grade 2 * Ventricular arrhythmias requiring continuous therapy * Uncontrolled supraventricular arrhythmias including atrial fibrillation * Haemorrhagic or thrombotic stroke, including transient ischaemic attacks or other central nervous system bleeding * Abnormal echocardiogram at baseline (left ventricular ejection fraction \[LVEF\] \<55% and shortening fraction \[SF\] \<15%) * Torsades de Pointes either currently or within 12 months * Mean resting QTcF ≥470 ms * Medications known to prolong QT interval, or that increase the risk of QTc prolongation or arrhythmic events (such as heart failure, hypokalaemia, congenital long QT syndrome, family history of either long QT syndrome), or unexplained sudden death under 40 years of age * Laboratory values as listed below: * Absolute neutrophil count \<1.5x109/L * Platelet count \<100x109/L * Haemoglobin \<90 g/L * Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>2.5 times upper limit of normal (ULN) if no demonstrable liver metastases or \>5xULN in the presence of liver metastases * Total bilirubin \>1.5xULN if no demonstrable liver metastases or \>3xULN in the presence of liver metastases * Serum creatinine \>1.5xULN concurrent with creatinine clearance \<50 mL/min (measured or calculated by Cockcroft and Gault equation), confirmation of creatinine clearance is only required when creatinine is \>1.5xULN * Clinically relevant and treatment resistant abnormalities in potassium, sodium, calcium (corrected for plasma albumin) or magnesium * Pre-existing renal disease including glomerulonephritis, nephritic syndrome, Fanconi Syndrome or renal tubular acidosis * Abnormal fasting glucose \>126 mg/dL (\>7 mmol/L) * Patients with diabetes Type 1 or uncontrolled Type 2 (glycosylated haemoglobin \[HbA1c\] \>8% \[64 mmol/mol\] assessed locally) * Current refractory nausea and vomiting, chronic gastrointestinal disease or inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption * History of hypersensitivity to active or inactive excipients of AZD2014 or drugs with a similar chemical structure or class to AZD2014 * Judgment that patient is unsuitable to participate in study and unlikely to comply with study procedures, restrictions & requirements

Design outcomes

Primary

Measure	Time frame	Description
Cumulative Percentage of Total [14C] Radioactivity Excreted in Stool as a Percentage of the Dose (fe Cum%[f])	Stool was collected during the following periods: 0-6, 6-12, 12-24, 24-48, 48-72, 72-96, 96-120, 120-144 and 144-168 h post [14C]-AZD2014 dose in the Single Dose Period.	fe cum%(f) by the end of each collection period is presented following administration of \[14C\]-AZD2014. Radioactivity excreta data for 1 patient was not included due to technical issues with radioactivity sample collection.
Fraction of AZD2014 Excreted in Urine as a Percentage of the Dose (fe%[R])	Urine was collected during the following periods: 0-6, 6-12, 12-24, 24-48, 48-72, 72-96, 96-120, 120-144 and 144-168 h post [14C]-AZD2014 dose in the Single Dose Period.	Mean fe%(R) values per urine collection period are presented as a percentage of the total \[14C\]-AZD2014 dose administered on Day 1.
Renal Clearance (CL[R]) of AZD2014 From Plasma.	Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose in the Single Dose Period.	CL(R) of AZD2014 from plasma up to 168 h post-dose.
Cumulative Percentage of Total [14C] Radioactivity Excreted in Urine as a Percentage of the Dose (fe Cum%[R])	Urine was collected during the following periods: 0-6, 6-12, 12-24, 24-48, 48-72, 72-96, 96-120, 120-144 and 144-168 h post [14C]-AZD2014 dose in the Single Dose Period.	fe cum%(R) by the end of each collection period is presented following administration of \[14C\]-AZD2014. Radioactivity excreta data for 1 patient was not included due to technical issues with radioactivity sample collection.
Total Radioactivity in Plasma Following Administration of [14C]-AZD2014	Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32 and 48 hours (h) post [14C]-AZD2014 dose in the Single Dose Period.	The mean concentrations of total radioactivity in plasma collected from each patient who received a single oral dose of 125 mg \[14C\]-AZD2014 are presented for time points of plasma sampling up to 48 hours post-dose. Geometric mean concentrations were not quantifiable after 48 hours. The total \[14C\] radioactivity in plasma was converted to concentration equivalents of AZD2014 based on the actual specific activity of the dose.
AZD2014 Concentrations in Plasma Following Administration of [14C]-AZD2014	Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 h post [14C]-AZD2014 dose in the Single Dose Period.	The mean concentrations of AZD2014 in plasma collected from each patient who received a single oral dose of 125 mg \[14C\]-AZD2014 are presented for time points of plasma sampling up to 24 hours post-dose. Geometric mean concentrations were not quantifiable after 24 hours.
Total Radioactivity Concentrations in Saliva Following Administration of [14C]-AZD2014	Saliva was collected at 1, 2, 4, 6, 8, 10 and 12 h post [14C]-AZD2014 dose in the Single Dose Period.	The mean concentrations of total radioactivity in saliva collected from each patient who received a single oral dose of 125 mg \[14C\]-AZD2014 are presented for time points of saliva collection up to 12 hours post-dose. Geometric mean concentrations were not quantifiable after 12 hours. The total \[14C\] radioactivity in saliva was converted to concentration equivalents of AZD2014 based on the actual specific activity of the dose.
AZD2014 Concentrations in Saliva Following Administration of [14C]-AZD2014	Saliva was collected at 1, 2, 4, 6, 8, 10 and 12 h post [14C]-AZD2014 dose in the Single Dose Period.	The mean concentrations of AZD2014 in saliva collected from each patient who received a single oral dose of 125 mg \[14C\]-AZD2014 are presented for time points of plasma sampling up to 12 hours post-dose. Geometric mean concentrations were not quantifiable after 12 hours.
Total Radioactivity Concentrations in Blood Following Administration of [14C]-AZD2014	Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 h post [14C]-AZD2014 dose in the Single Dose Period.	The mean concentrations of total radioactivity in blood collected from each patient who received a single oral dose of 125 mg \[14C\]-AZD2014 are presented for time points of blood sampling up to 12 hours post-dose. Geometric mean concentrations were not quantifiable after 12 hours. The total \[14C\] radioactivity in plasma was converted to concentration equivalents of AZD2014 based on the actual specific activity of the dose.
Cumulative Percentage of [14C]-AZD2014 Recovered by Day 8	From pre-dose Day 1 to Day 8 of the Single Dose Period.	The mean cumulative percentage of \[14C\]-AZD2014 dose recovered as total radioactivity by the end of the Single Dose Period (Day 1 - 8) is presented. The total \[14C\] radioactivity in plasma was converted to concentration equivalents of AZD2014 based on the actual specific activity of the dose. Radioactivity excreta data for 1 patient was not included due to technical issues with radioactivity sample collection.
Maximum Observed Concentration (Cmax) of AZD2014 in Plasma and Saliva	Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose. Saliva was collected at 1, 2, 4, 6, 8, 10, 12 and 24 h post [14C]-AZD2014 dose in the Single Dose Period.	Mean AZD2014 Cmax values in plasma and saliva following administration of \[14C\]-AZD2014 on Day 1 are presented.
Time to Maximum Observed Concentration (Tmax) for AZD2014 in Plasma and Saliva	Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose. Saliva was collected at 1, 2, 4, 6, 8, 10, 12 and 24 h post [14C]-AZD2014 dose in the Single Dose Period.	AZD2014 Tmax values for plasma and saliva following administration of \[14C\]-AZD2014 on Day 1 are presented.
Time to Last Measurable Concentration (t[Last]) for AZD2014 in Plasma and Saliva	Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose. Saliva was collected at 1, 2, 4, 6, 8, 10, 12 and 24 h post [14C]-AZD2014 dose in the Single Dose Period.	AZD2014 t(last) values in plasma and saliva following administration of \[14C\]-AZD2014 on Day 1 are presented.
Area Under the Plasma Concentration-time Curve (AUC) for AZD2014	Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose in the Single Dose Period.	Mean AUC for AZD2014 following administration of \[14C\]-AZD2014 on Day 1 is presented.
Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC[0-t]) for AZD2014 in Plasma and Saliva	Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose. Saliva was collected at 1, 2, 4, 6, 8, 10, 12 and 24 h post [14C]-AZD2014 dose in the Single Dose Period.	Mean AUC(0-t) values in plasma and saliva for AZD2014 following administration of \[14C\]-AZD2014 on Day 1 are presented.
Apparent Total Body Clearance (CL/F) of AZD2014	Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose in the Single Dose Period.	The mean CL/F of AZD2014 in plasma following administration of \[14C\]-AZD2014 on Day 1 is presented.
Mean Residence Time (MRT) of AZD2014	Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose in the Single Dose Period.	The MRT of AZD2014 in plasma following administration of \[14C\]-AZD2014 on Day 1 is presented.
Apparent Volume of Distribution at Steady State (Vss/F) for AZD2014 in Plasma	Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose in the Single Dose Period.	The mean Vss/F of AZD2014 in plasma following administration of \[14C\]-AZD2014 on Day 1 is presented.
Terminal Elimination Rate Constant (lambda_z) for AZD2014 in Plasma	Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose in the Single Dose Period.	The mean lambda\_z of AZD2014 in plasma following administration of \[14C\]-AZD2014 on Day 1 is presented.
Half-life Associated With Terminal Slope (lambda_z) of a Semi-logarithmic Concentration-time Curve (t1/2[lambda_z]) for AZD2014 in Plasma	Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h ost [14C]-AZD2014 dose in the Single Dose Period.	The mean t1/2(lambda\_z) for AZD2014 in plasma following administration of \[14C\]-AZD2014 on Day 1 is presented.
Cmax for Total [14C] Radioactivity in Whole Blood and Saliva	Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose. Saliva was collected at 1, 2, 4, 6, 8, 10, 12 and 24 h post [14C]-AZD2014 dose in the Single Dose Period.	Mean \[14C\] radioactivity Cmax values in whole blood and saliva following administration of \[14C\]-AZD2014 on Day 1 are presented.
Tmax for [14C] Radioactivity in Whole Blood and Saliva	Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose. Saliva was collected at 1, 2, 4, 6, 8, 10, 12 and 24 h post [14C]-AZD2014 dose in the Single Dose Period.	\[14C\] radioactivity tmax in whole blood and saliva following administration of \[14C\]-AZD2014 on Day 1 is presented .
T(Last) for [14C] Radioactivity in Whole Blood and Saliva	Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose. Saliva was collected at 1, 2, 4, 6, 8, 10, 12 and 24 h post [14C]-AZD2014 dose in the Single Dose Period.	Mean \[14C\] radioactivity t(last) values in whole blood and saliva following administration of \[14C\]-AZD2014 on Day 1 are presented.
Ratio of Whole Blood Total Radioactivity to Plasma Total Radioactivity	Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 h post [14C]-AZD2014 dose.	The mean ratios of whole blood total radioactivity to plasma total radioactivity are presented for the timepoints of sample collection up to 12 hours post-dose. Geometric mean ratios were not calculated after 12 hours.
Ratio of AZD2014 Concentration to Total Radioactivity Concentration in Saliva	Saliva was collected at 1, 2, 4, 6, 8 and 10 h post [14C]-AZD2014 dose in the Single Dose Period.	The mean ratios of saliva AZD2014 to saliva radioactivity concentrations are presented for the timepoints of saliva collection up to 10 hours post-dose. Geometric mean ratios were not calculated after 10 hours. Radioactivity excreta data for 1 patient was not included due to technical issues with radioactivity sample collection.

Secondary

Measure	Time frame	Description
Best Overall Response (BOR) Assessment	RECIST 1.1 assessments were performed pre-dose at screening and then once every 8 weeks relative to the start of treatment in the Multiple Dose Period.	Anti-tumour activity through assessment of BOR. BOR was defined for each patient as follows according to the RECIST 1.1 criteria: Complete Response (CR): Disappearance of all target lesions since baseline. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions. Stable Disease (SD): Any cases that do not qualify for either PR or progressive disease (PD). PD: At least a 20% increase in the sum of the diameters of target lesions. BOR for each patient was determined as the best response recorded from the day study treatment started until progression or until the last evaluable RECIST tumour assessment in the absence of progression.
Best Percentage Change in Tumour Size From Baseline	RECIST 1.1 assessments were performed pre-dose at screening and then once every 8 weeks relative to the start of treatment in the Multiple Dose Period.	Assessment of anti-tumour activity through measurement of tumour lesions. Tumour size was defined as the sum of the lengths of the longest diameters of the RECIST 1.1 target lesions.
Number of AEs Experienced by Patients.	From Day 1 of the Single Dose Period to 30 days after the last dose of AZD2014 administered in the Multiple Dose Period.	AEs (including serious AEs \[SAEs\]) were collected from the time of informed consent (Visit 1) and throughout the study, including the 30-day follow-up. The numbers of patients experiencing any AEs and SAEs, causally related AEs and SAEs, and SAEs which were fatal are presented.

Countries

United Kingdom

Participant flow

Recruitment details

First subject enrolled: 8 February 2016; Last Subject Last Visit: 21 December 2016 (End of Study \[EoS\]). The study was performed at a single study centre in the United Kingdom. Adult patients with advanced solid tumours refractory or resistant to standard therapies were recruited into this 2 period study.

Pre-assignment details

4 patients were enrolled (signed informed consent). Following \[14C\]-AZD2014, patients either continued AZD2014 as monotherapy or in combination with a standard regimen of fulvestrant or paclitaxel as appropriate and at the Investigator's discretion. No patients were recruited into AZD2014+paclitaxel treatment regimen.

Participants by arm

Arm	Count
[14C]-AZD2014 Then AZD2014 Monotherapy Single Dose Period: Patients were given a single oral dose of \[14C\]-AZD2014 as an oral solution on Day 1 of the first treatment period (Cycle 0). Patients were admitted to the study clinic pre-dose on Day 1 until at least Day 8 (168 hours post-dose). Multiple Dose Period: From Day 1 Cycle 1, patients could continue non-radiolabelled AZD2014 (AZD2014 monotherapy), which was administered as an oral tablet. Patients continued treatment as outpatients until withdrawal due to AEs, withdrawal of consent, progression of disease according to RECIST 1.1, until the patient was no longer receiving clinical benefit or the patient started any new anti-cancer therapy.	3
[14C]-AZD2014 Then AZD2014 + Fulvestrant Single Dose Period: Patients were given a single oral dose of \[14C\]-AZD2014 as an oral solution on Day 1 of the first treatment period (Cycle 0). Patients were admitted to the study clinic pre-dose on Day 1 until at least Day 8 (168 hours post-dose). Multiple Dose Period: From Day 1 Cycle 1, patients could continue AZD2014, which was administered as an oral tablet, in combination with standard regimens of fulvestrant therapy. Patients continued treatment as outpatients until withdrawal due to AEs, withdrawal of consent, progression of disease according to RECIST 1.1, until the patient was no longer receiving clinical benefit or the patient started any new anti-cancer therapy.	1
Total	4

Withdrawals & dropouts

Period	Reason	FG000	FG001
Multiple Dose Period (Day 8 - EoS)	Condition under investigation worsened	0	1
Multiple Dose Period (Day 8 - EoS)	Subjective progression of disease	1	0
Multiple Dose Period (Day 8 - EoS)	Withdrawal by Subject	1	0

Baseline characteristics

Characteristic	[14C]-AZD2014 Then AZD2014 Monotherapy	[14C]-AZD2014 Then AZD2014 + Fulvestrant	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	1 Participants	0 Participants	1 Participants
Age, Categorical Between 18 and 65 years	2 Participants	1 Participants	3 Participants
Sex: Female, Male Female	2 Participants	1 Participants	3 Participants
Sex: Female, Male Male	1 Participants	0 Participants	1 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	3 / 3	1 / 1
serious Total, serious adverse events	1 / 3	1 / 1

Outcome results

Primary

Apparent Total Body Clearance (CL/F) of AZD2014

The mean CL/F of AZD2014 in plasma following administration of \[14C\]-AZD2014 on Day 1 is presented.

Time frame: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose in the Single Dose Period.

Population: The PK analysis population consisted of all evaluable patients who were dosed with \[14C\]-AZD2014 in Cycle 0 and who had reportable and evaluable PK concentration data. Patients were excluded if they vomited at or before 3 hours post-dosing or had identified procedural or scientific deficiency as being likely to impact the PK data.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Apparent Total Body Clearance (CL/F) of AZD2014	7.282 L/h	Geometric Coefficient of Variation 29.8

Primary

Apparent Volume of Distribution at Steady State (Vss/F) for AZD2014 in Plasma

The mean Vss/F of AZD2014 in plasma following administration of \[14C\]-AZD2014 on Day 1 is presented.

Time frame: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose in the Single Dose Period.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Apparent Volume of Distribution at Steady State (Vss/F) for AZD2014 in Plasma	37.86 L	Geometric Coefficient of Variation 31.68

Primary

Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC[0-t]) for AZD2014 in Plasma and Saliva

Mean AUC(0-t) values in plasma and saliva for AZD2014 following administration of \[14C\]-AZD2014 on Day 1 are presented.

Time frame: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose. Saliva was collected at 1, 2, 4, 6, 8, 10, 12 and 24 h post [14C]-AZD2014 dose in the Single Dose Period.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC[0-t]) for AZD2014 in Plasma and Saliva	AUC(0-t) in plasma	16510 h*ng/mL	Geometric Coefficient of Variation 29.31
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC[0-t]) for AZD2014 in Plasma and Saliva	AUC(0-t) in saliva	6025 h*ng/mL	Geometric Coefficient of Variation 78.7

Primary

Area Under the Plasma Concentration-time Curve (AUC) for AZD2014

Mean AUC for AZD2014 following administration of \[14C\]-AZD2014 on Day 1 is presented.

Time frame: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose in the Single Dose Period.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Area Under the Plasma Concentration-time Curve (AUC) for AZD2014	17170 h*ng/mL	Geometric Coefficient of Variation 29.8

Primary

AZD2014 Concentrations in Plasma Following Administration of [14C]-AZD2014

The mean concentrations of AZD2014 in plasma collected from each patient who received a single oral dose of 125 mg \[14C\]-AZD2014 are presented for time points of plasma sampling up to 24 hours post-dose. Geometric mean concentrations were not quantifiable after 24 hours.

Time frame: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 h post [14C]-AZD2014 dose in the Single Dose Period.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
[14C]-AZD2014 (Period 1 [Day 1 - 8])	AZD2014 Concentrations in Plasma Following Administration of [14C]-AZD2014	1 h (n = 4)	3090 ng/mL	Geometric Coefficient of Variation 39.49
[14C]-AZD2014 (Period 1 [Day 1 - 8])	AZD2014 Concentrations in Plasma Following Administration of [14C]-AZD2014	0.5 h (n = 3)	3704 ng/mL	Geometric Coefficient of Variation 29.79
[14C]-AZD2014 (Period 1 [Day 1 - 8])	AZD2014 Concentrations in Plasma Following Administration of [14C]-AZD2014	1.5 h (n = 4)	2758 ng/mL	Geometric Coefficient of Variation 26.33
[14C]-AZD2014 (Period 1 [Day 1 - 8])	AZD2014 Concentrations in Plasma Following Administration of [14C]-AZD2014	2 h (n = 4)	2409 ng/mL	Geometric Coefficient of Variation 22.11
[14C]-AZD2014 (Period 1 [Day 1 - 8])	AZD2014 Concentrations in Plasma Following Administration of [14C]-AZD2014	3 h (n = 4)	1768 ng/mL	Geometric Coefficient of Variation 26.45
[14C]-AZD2014 (Period 1 [Day 1 - 8])	AZD2014 Concentrations in Plasma Following Administration of [14C]-AZD2014	4 h (n = 4)	1439 ng/mL	Geometric Coefficient of Variation 43.74
[14C]-AZD2014 (Period 1 [Day 1 - 8])	AZD2014 Concentrations in Plasma Following Administration of [14C]-AZD2014	6 h (n = 4)	917.7 ng/mL	Geometric Coefficient of Variation 8.278
[14C]-AZD2014 (Period 1 [Day 1 - 8])	AZD2014 Concentrations in Plasma Following Administration of [14C]-AZD2014	8 h (n = 4)	619.4 ng/mL	Geometric Coefficient of Variation 40.08
[14C]-AZD2014 (Period 1 [Day 1 - 8])	AZD2014 Concentrations in Plasma Following Administration of [14C]-AZD2014	12 h (n = 4)	314.6 ng/mL	Geometric Coefficient of Variation 67.36
[14C]-AZD2014 (Period 1 [Day 1 - 8])	AZD2014 Concentrations in Plasma Following Administration of [14C]-AZD2014	24 h (n = 2)	35.11 ng/mL	Geometric Coefficient of Variation 103.2

Primary

AZD2014 Concentrations in Saliva Following Administration of [14C]-AZD2014

The mean concentrations of AZD2014 in saliva collected from each patient who received a single oral dose of 125 mg \[14C\]-AZD2014 are presented for time points of plasma sampling up to 12 hours post-dose. Geometric mean concentrations were not quantifiable after 12 hours.

Time frame: Saliva was collected at 1, 2, 4, 6, 8, 10 and 12 h post [14C]-AZD2014 dose in the Single Dose Period.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
[14C]-AZD2014 (Period 1 [Day 1 - 8])	AZD2014 Concentrations in Saliva Following Administration of [14C]-AZD2014	1 h (n = 3)	4159 ng/mL	Geometric Coefficient of Variation 84.68
[14C]-AZD2014 (Period 1 [Day 1 - 8])	AZD2014 Concentrations in Saliva Following Administration of [14C]-AZD2014	2 h (n = 4)	416.3 ng/mL	Geometric Coefficient of Variation 84.85
[14C]-AZD2014 (Period 1 [Day 1 - 8])	AZD2014 Concentrations in Saliva Following Administration of [14C]-AZD2014	4 h (n = 4)	169.1 ng/mL	Geometric Coefficient of Variation 52.5
[14C]-AZD2014 (Period 1 [Day 1 - 8])	AZD2014 Concentrations in Saliva Following Administration of [14C]-AZD2014	6 h (n = 4)	75.08 ng/mL	Geometric Coefficient of Variation 40.23
[14C]-AZD2014 (Period 1 [Day 1 - 8])	AZD2014 Concentrations in Saliva Following Administration of [14C]-AZD2014	8 h (n = 4)	73.27 ng/mL	Geometric Coefficient of Variation 15.19
[14C]-AZD2014 (Period 1 [Day 1 - 8])	AZD2014 Concentrations in Saliva Following Administration of [14C]-AZD2014	10 h (n = 3)	32.59 ng/mL	Geometric Coefficient of Variation 60.47
[14C]-AZD2014 (Period 1 [Day 1 - 8])	AZD2014 Concentrations in Saliva Following Administration of [14C]-AZD2014	12 h (n = 2)	33.96 ng/mL	Geometric Coefficient of Variation 69.25

Primary

Cmax for Total [14C] Radioactivity in Whole Blood and Saliva

Mean \[14C\] radioactivity Cmax values in whole blood and saliva following administration of \[14C\]-AZD2014 on Day 1 are presented.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Cmax for Total [14C] Radioactivity in Whole Blood and Saliva	Cmax in whole blood	3004 ngEq/mL	Geometric Coefficient of Variation 36.91
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Cmax for Total [14C] Radioactivity in Whole Blood and Saliva	Cmax in saliva	6966 ngEq/mL	Geometric Coefficient of Variation 76.9

Primary

Cumulative Percentage of [14C]-AZD2014 Recovered by Day 8

The mean cumulative percentage of \[14C\]-AZD2014 dose recovered as total radioactivity by the end of the Single Dose Period (Day 1 - 8) is presented. The total \[14C\] radioactivity in plasma was converted to concentration equivalents of AZD2014 based on the actual specific activity of the dose. Radioactivity excreta data for 1 patient was not included due to technical issues with radioactivity sample collection.

Time frame: From pre-dose Day 1 to Day 8 of the Single Dose Period.

Arm	Measure	Value (MEAN)	Dispersion
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Cumulative Percentage of [14C]-AZD2014 Recovered by Day 8	92.02 Percentage of dose administered	Standard Deviation 1.994

Primary

Cumulative Percentage of Total [14C] Radioactivity Excreted in Stool as a Percentage of the Dose (fe Cum%[f])

fe cum%(f) by the end of each collection period is presented following administration of \[14C\]-AZD2014. Radioactivity excreta data for 1 patient was not included due to technical issues with radioactivity sample collection.

Time frame: Stool was collected during the following periods: 0-6, 6-12, 12-24, 24-48, 48-72, 72-96, 96-120, 120-144 and 144-168 h post [14C]-AZD2014 dose in the Single Dose Period.

Arm	Measure	Group	Value (MEAN)	Dispersion
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Cumulative Percentage of Total [14C] Radioactivity Excreted in Stool as a Percentage of the Dose (fe Cum%[f])	0 - 24 h	18.23 Cumulative % of total [14C]-AZD2014 dose	Standard Deviation 21.55
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Cumulative Percentage of Total [14C] Radioactivity Excreted in Stool as a Percentage of the Dose (fe Cum%[f])	0 - 48 h	52.85 Cumulative % of total [14C]-AZD2014 dose	Standard Deviation 5.033
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Cumulative Percentage of Total [14C] Radioactivity Excreted in Stool as a Percentage of the Dose (fe Cum%[f])	0 - 72 h	77.04 Cumulative % of total [14C]-AZD2014 dose	Standard Deviation 6.843
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Cumulative Percentage of Total [14C] Radioactivity Excreted in Stool as a Percentage of the Dose (fe Cum%[f])	0 - 96 h	78.59 Cumulative % of total [14C]-AZD2014 dose	Standard Deviation 6.029
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Cumulative Percentage of Total [14C] Radioactivity Excreted in Stool as a Percentage of the Dose (fe Cum%[f])	0 - 120 h	79.25 Cumulative % of total [14C]-AZD2014 dose	Standard Deviation 5.39
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Cumulative Percentage of Total [14C] Radioactivity Excreted in Stool as a Percentage of the Dose (fe Cum%[f])	0 - 144 h	79.70 Cumulative % of total [14C]-AZD2014 dose	Standard Deviation 5.167
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Cumulative Percentage of Total [14C] Radioactivity Excreted in Stool as a Percentage of the Dose (fe Cum%[f])	0 - 168 h	79.94 Cumulative % of total [14C]-AZD2014 dose	Standard Deviation 4.955

Primary

Cumulative Percentage of Total [14C] Radioactivity Excreted in Urine as a Percentage of the Dose (fe Cum%[R])

fe cum%(R) by the end of each collection period is presented following administration of \[14C\]-AZD2014. Radioactivity excreta data for 1 patient was not included due to technical issues with radioactivity sample collection.

Time frame: Urine was collected during the following periods: 0-6, 6-12, 12-24, 24-48, 48-72, 72-96, 96-120, 120-144 and 144-168 h post [14C]-AZD2014 dose in the Single Dose Period.

Arm	Measure	Group	Value (MEAN)	Dispersion
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Cumulative Percentage of Total [14C] Radioactivity Excreted in Urine as a Percentage of the Dose (fe Cum%[R])	0 - 6 h	5.514 Cumulative % of total [14C]-AZD2014 dose	Standard Deviation 3.917
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Cumulative Percentage of Total [14C] Radioactivity Excreted in Urine as a Percentage of the Dose (fe Cum%[R])	0 - 12 h	8.990 Cumulative % of total [14C]-AZD2014 dose	Standard Deviation 4.711
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Cumulative Percentage of Total [14C] Radioactivity Excreted in Urine as a Percentage of the Dose (fe Cum%[R])	0 - 24 h	11.06 Cumulative % of total [14C]-AZD2014 dose	Standard Deviation 5.13
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Cumulative Percentage of Total [14C] Radioactivity Excreted in Urine as a Percentage of the Dose (fe Cum%[R])	0 - 48 h	11.81 Cumulative % of total [14C]-AZD2014 dose	Standard Deviation 5.294
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Cumulative Percentage of Total [14C] Radioactivity Excreted in Urine as a Percentage of the Dose (fe Cum%[R])	0 - 72 h	11.96 Cumulative % of total [14C]-AZD2014 dose	Standard Deviation 5.378
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Cumulative Percentage of Total [14C] Radioactivity Excreted in Urine as a Percentage of the Dose (fe Cum%[R])	0 - 96 h	12.03 Cumulative % of total [14C]-AZD2014 dose	Standard Deviation 5.416
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Cumulative Percentage of Total [14C] Radioactivity Excreted in Urine as a Percentage of the Dose (fe Cum%[R])	0 - 120 h	12.07 Cumulative % of total [14C]-AZD2014 dose	Standard Deviation 5.441
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Cumulative Percentage of Total [14C] Radioactivity Excreted in Urine as a Percentage of the Dose (fe Cum%[R])	0 - 144 h	12.07 Cumulative % of total [14C]-AZD2014 dose	Standard Deviation 5.441
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Cumulative Percentage of Total [14C] Radioactivity Excreted in Urine as a Percentage of the Dose (fe Cum%[R])	0 - 168 h	12.08 Cumulative % of total [14C]-AZD2014 dose	Standard Deviation 5.453

Primary

Fraction of AZD2014 Excreted in Urine as a Percentage of the Dose (fe%[R])

Mean fe%(R) values per urine collection period are presented as a percentage of the total \[14C\]-AZD2014 dose administered on Day 1.

Time frame: Urine was collected during the following periods: 0-6, 6-12, 12-24, 24-48, 48-72, 72-96, 96-120, 120-144 and 144-168 h post [14C]-AZD2014 dose in the Single Dose Period.

Arm	Measure	Group	Value (MEAN)	Dispersion
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Fraction of AZD2014 Excreted in Urine as a Percentage of the Dose (fe%[R])	0 - 6 h	1.575 % of total [14C]-AZD2014 dose	Standard Deviation 1.165
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Fraction of AZD2014 Excreted in Urine as a Percentage of the Dose (fe%[R])	6 - 12 h	0.7471 % of total [14C]-AZD2014 dose	Standard Deviation 0.7198
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Fraction of AZD2014 Excreted in Urine as a Percentage of the Dose (fe%[R])	12 - 24 h	0.3472 % of total [14C]-AZD2014 dose	Standard Deviation 0.3251
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Fraction of AZD2014 Excreted in Urine as a Percentage of the Dose (fe%[R])	24 - 48 h	0.0460 % of total [14C]-AZD2014 dose	Standard Deviation 0.0697
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Fraction of AZD2014 Excreted in Urine as a Percentage of the Dose (fe%[R])	48 - 72 h	0 % of total [14C]-AZD2014 dose	Standard Deviation 0
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Fraction of AZD2014 Excreted in Urine as a Percentage of the Dose (fe%[R])	72 - 96 h	0 % of total [14C]-AZD2014 dose	Standard Deviation 0
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Fraction of AZD2014 Excreted in Urine as a Percentage of the Dose (fe%[R])	96 - 120 h	0 % of total [14C]-AZD2014 dose	Standard Deviation 0
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Fraction of AZD2014 Excreted in Urine as a Percentage of the Dose (fe%[R])	120 - 144 h	NA % of total [14C]-AZD2014 dose	—
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Fraction of AZD2014 Excreted in Urine as a Percentage of the Dose (fe%[R])	144 - 168 h	0 % of total [14C]-AZD2014 dose	Standard Deviation 0

Primary

Half-life Associated With Terminal Slope (lambda_z) of a Semi-logarithmic Concentration-time Curve (t1/2[lambda_z]) for AZD2014 in Plasma

The mean t1/2(lambda\_z) for AZD2014 in plasma following administration of \[14C\]-AZD2014 on Day 1 is presented.

Time frame: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h ost [14C]-AZD2014 dose in the Single Dose Period.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Half-life Associated With Terminal Slope (lambda_z) of a Semi-logarithmic Concentration-time Curve (t1/2[lambda_z]) for AZD2014 in Plasma	3.571 h	Geometric Coefficient of Variation 32.54

Primary

Maximum Observed Concentration (Cmax) of AZD2014 in Plasma and Saliva

Mean AZD2014 Cmax values in plasma and saliva following administration of \[14C\]-AZD2014 on Day 1 are presented.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Maximum Observed Concentration (Cmax) of AZD2014 in Plasma and Saliva	Cmax in plasma	4254 ng/mL	Geometric Coefficient of Variation 37.73
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Maximum Observed Concentration (Cmax) of AZD2014 in Plasma and Saliva	Cmax in saliva	5410 ng/mL	Geometric Coefficient of Variation 94.34

Primary

Mean Residence Time (MRT) of AZD2014

The MRT of AZD2014 in plasma following administration of \[14C\]-AZD2014 on Day 1 is presented.

Time frame: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose in the Single Dose Period.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Mean Residence Time (MRT) of AZD2014	5.200 h	Geometric Coefficient of Variation 27.98

Primary

Ratio of AZD2014 Concentration to Total Radioactivity Concentration in Saliva

The mean ratios of saliva AZD2014 to saliva radioactivity concentrations are presented for the timepoints of saliva collection up to 10 hours post-dose. Geometric mean ratios were not calculated after 10 hours. Radioactivity excreta data for 1 patient was not included due to technical issues with radioactivity sample collection.

Time frame: Saliva was collected at 1, 2, 4, 6, 8 and 10 h post [14C]-AZD2014 dose in the Single Dose Period.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Ratio of AZD2014 Concentration to Total Radioactivity Concentration in Saliva	2 h	0.8217 ng/mL:ngEq/mL	Geometric Coefficient of Variation 18.2
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Ratio of AZD2014 Concentration to Total Radioactivity Concentration in Saliva	1 h	1.011 ng/mL:ngEq/mL	Geometric Coefficient of Variation 5.35
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Ratio of AZD2014 Concentration to Total Radioactivity Concentration in Saliva	4 h	0.7001 ng/mL:ngEq/mL	Geometric Coefficient of Variation 6.167
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Ratio of AZD2014 Concentration to Total Radioactivity Concentration in Saliva	6 h	0.4993 ng/mL:ngEq/mL	Geometric Coefficient of Variation 28.85
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Ratio of AZD2014 Concentration to Total Radioactivity Concentration in Saliva	8 h	0.4671 ng/mL:ngEq/mL	Geometric Coefficient of Variation 45.52
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Ratio of AZD2014 Concentration to Total Radioactivity Concentration in Saliva	10 h	0.3648 ng/mL:ngEq/mL	Geometric Coefficient of Variation 21.01

Primary

Ratio of Whole Blood Total Radioactivity to Plasma Total Radioactivity

The mean ratios of whole blood total radioactivity to plasma total radioactivity are presented for the timepoints of sample collection up to 12 hours post-dose. Geometric mean ratios were not calculated after 12 hours.

Time frame: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 h post [14C]-AZD2014 dose.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Ratio of Whole Blood Total Radioactivity to Plasma Total Radioactivity	1 h	0.6713 ngEq/mL:ngEq/mL	Geometric Coefficient of Variation 9.982
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Ratio of Whole Blood Total Radioactivity to Plasma Total Radioactivity	0.5 h	0.6861 ngEq/mL:ngEq/mL	Geometric Coefficient of Variation 8.213
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Ratio of Whole Blood Total Radioactivity to Plasma Total Radioactivity	1.5 h	0.6825 ngEq/mL:ngEq/mL	Geometric Coefficient of Variation 7.089
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Ratio of Whole Blood Total Radioactivity to Plasma Total Radioactivity	2 h	0.6623 ngEq/mL:ngEq/mL	Geometric Coefficient of Variation 5.377
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Ratio of Whole Blood Total Radioactivity to Plasma Total Radioactivity	3 h	0.6750 ngEq/mL:ngEq/mL	Geometric Coefficient of Variation 5.583
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Ratio of Whole Blood Total Radioactivity to Plasma Total Radioactivity	4 h	0.6904 ngEq/mL:ngEq/mL	Geometric Coefficient of Variation 8.647
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Ratio of Whole Blood Total Radioactivity to Plasma Total Radioactivity	6 h	0.6797 ngEq/mL:ngEq/mL	Geometric Coefficient of Variation 7.197
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Ratio of Whole Blood Total Radioactivity to Plasma Total Radioactivity	8 h	0.6917 ngEq/mL:ngEq/mL	Geometric Coefficient of Variation 11.16
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Ratio of Whole Blood Total Radioactivity to Plasma Total Radioactivity	12 h	0.7211 ngEq/mL:ngEq/mL	Geometric Coefficient of Variation 8.798

Primary

Renal Clearance (CL[R]) of AZD2014 From Plasma.

CL(R) of AZD2014 from plasma up to 168 h post-dose.

Time frame: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose in the Single Dose Period.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Renal Clearance (CL[R]) of AZD2014 From Plasma.	0.1596 L/h	Geometric Coefficient of Variation 78.34

Primary

Terminal Elimination Rate Constant (lambda_z) for AZD2014 in Plasma

The mean lambda\_z of AZD2014 in plasma following administration of \[14C\]-AZD2014 on Day 1 is presented.

Time frame: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32, 48, 72, 96, 120, 144 and 168 h post [14C]-AZD2014 dose in the Single Dose Period.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Terminal Elimination Rate Constant (lambda_z) for AZD2014 in Plasma	0.1941 1/h	Geometric Coefficient of Variation 32.54

Primary

Time to Last Measurable Concentration (t[Last]) for AZD2014 in Plasma and Saliva

AZD2014 t(last) values in plasma and saliva following administration of \[14C\]-AZD2014 on Day 1 are presented.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Time to Last Measurable Concentration (t[Last]) for AZD2014 in Plasma and Saliva	t(last) in plasma	17.04 h	Geometric Coefficient of Variation 41.33
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Time to Last Measurable Concentration (t[Last]) for AZD2014 in Plasma and Saliva	t(last) in saliva	10.57 h	Geometric Coefficient of Variation 21.76

Primary

Time to Maximum Observed Concentration (Tmax) for AZD2014 in Plasma and Saliva

AZD2014 Tmax values for plasma and saliva following administration of \[14C\]-AZD2014 on Day 1 are presented.

Arm	Measure	Group	Value (MEDIAN)	Dispersion
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Time to Maximum Observed Concentration (Tmax) for AZD2014 in Plasma and Saliva	Tmax in plasma	0.53 h	Full Range 37.73
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Time to Maximum Observed Concentration (Tmax) for AZD2014 in Plasma and Saliva	Tmax in saliva	1.00 h	—

Primary

T(Last) for [14C] Radioactivity in Whole Blood and Saliva

Mean \[14C\] radioactivity t(last) values in whole blood and saliva following administration of \[14C\]-AZD2014 on Day 1 are presented.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
[14C]-AZD2014 (Period 1 [Day 1 - 8])	T(Last) for [14C] Radioactivity in Whole Blood and Saliva	t(last) in whole blood	18.26 h	Geometric Coefficient of Variation 53.16
[14C]-AZD2014 (Period 1 [Day 1 - 8])	T(Last) for [14C] Radioactivity in Whole Blood and Saliva	t(last) in saliva	15.33 h	Geometric Coefficient of Variation 39.24

Primary

Tmax for [14C] Radioactivity in Whole Blood and Saliva

\[14C\] radioactivity tmax in whole blood and saliva following administration of \[14C\]-AZD2014 on Day 1 is presented .

Arm	Measure	Group	Value (MEDIAN)	Dispersion
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Tmax for [14C] Radioactivity in Whole Blood and Saliva	tmax in whole blood	0.53 h	Full Range 37.73
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Tmax for [14C] Radioactivity in Whole Blood and Saliva	tmax in saliva	1.00 h	—

Primary

Total Radioactivity Concentrations in Blood Following Administration of [14C]-AZD2014

The mean concentrations of total radioactivity in blood collected from each patient who received a single oral dose of 125 mg \[14C\]-AZD2014 are presented for time points of blood sampling up to 12 hours post-dose. Geometric mean concentrations were not quantifiable after 12 hours. The total \[14C\] radioactivity in plasma was converted to concentration equivalents of AZD2014 based on the actual specific activity of the dose.

Time frame: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 h post [14C]-AZD2014 dose in the Single Dose Period.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Total Radioactivity Concentrations in Blood Following Administration of [14C]-AZD2014	0.5 h (n = 3)	2725 ngEq/mL	Geometric Coefficient of Variation 38.13
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Total Radioactivity Concentrations in Blood Following Administration of [14C]-AZD2014	1 h (n = 4)	2293 ngEq/mL	Geometric Coefficient of Variation 42.5
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Total Radioactivity Concentrations in Blood Following Administration of [14C]-AZD2014	1.5 h (n = 4)	1980 ngEq/mL	Geometric Coefficient of Variation 36.01
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Total Radioactivity Concentrations in Blood Following Administration of [14C]-AZD2014	2 h (n = 4)	1783 ngEq/mL	Geometric Coefficient of Variation 36.48
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Total Radioactivity Concentrations in Blood Following Administration of [14C]-AZD2014	3 h (n = 4)	1421 ngEq/mL	Geometric Coefficient of Variation 38.64
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Total Radioactivity Concentrations in Blood Following Administration of [14C]-AZD2014	4 h (n = 4)	1255 ngEq/mL	Geometric Coefficient of Variation 37.07
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Total Radioactivity Concentrations in Blood Following Administration of [14C]-AZD2014	6 h (n = 4)	964.9 ngEq/mL	Geometric Coefficient of Variation 39.01
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Total Radioactivity Concentrations in Blood Following Administration of [14C]-AZD2014	8 h (n = 4)	632.1 ngEq/mL	Geometric Coefficient of Variation 43.65
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Total Radioactivity Concentrations in Blood Following Administration of [14C]-AZD2014	12 h (n = 4)	345.0 ngEq/mL	Geometric Coefficient of Variation 44.17

Primary

Total Radioactivity Concentrations in Saliva Following Administration of [14C]-AZD2014

The mean concentrations of total radioactivity in saliva collected from each patient who received a single oral dose of 125 mg \[14C\]-AZD2014 are presented for time points of saliva collection up to 12 hours post-dose. Geometric mean concentrations were not quantifiable after 12 hours. The total \[14C\] radioactivity in saliva was converted to concentration equivalents of AZD2014 based on the actual specific activity of the dose.

Time frame: Saliva was collected at 1, 2, 4, 6, 8, 10 and 12 h post [14C]-AZD2014 dose in the Single Dose Period.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Total Radioactivity Concentrations in Saliva Following Administration of [14C]-AZD2014	1 h (n = 2)	5495 ngEq/mL	Geometric Coefficient of Variation 89.69
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Total Radioactivity Concentrations in Saliva Following Administration of [14C]-AZD2014	2 h (n = 3)	650.2 ngEq/mL	Geometric Coefficient of Variation 52.98
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Total Radioactivity Concentrations in Saliva Following Administration of [14C]-AZD2014	4 h (n = 3)	264.3 ngEq/mL	Geometric Coefficient of Variation 62.1
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Total Radioactivity Concentrations in Saliva Following Administration of [14C]-AZD2014	6 h (n = 3)	135.4 ngEq/mL	Geometric Coefficient of Variation 73.87
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Total Radioactivity Concentrations in Saliva Following Administration of [14C]-AZD2014	8 h (n = 3)	158.5 ngEq/mL	Geometric Coefficient of Variation 33.15
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Total Radioactivity Concentrations in Saliva Following Administration of [14C]-AZD2014	10 h (n = 3)	105.2 ngEq/mL	Geometric Coefficient of Variation 39.57
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Total Radioactivity Concentrations in Saliva Following Administration of [14C]-AZD2014	12 h (n = 3)	104.0 ngEq/mL	Geometric Coefficient of Variation 48.01

Primary

Total Radioactivity in Plasma Following Administration of [14C]-AZD2014

The mean concentrations of total radioactivity in plasma collected from each patient who received a single oral dose of 125 mg \[14C\]-AZD2014 are presented for time points of plasma sampling up to 48 hours post-dose. Geometric mean concentrations were not quantifiable after 48 hours. The total \[14C\] radioactivity in plasma was converted to concentration equivalents of AZD2014 based on the actual specific activity of the dose.

Time frame: Blood samples collected: Day 1 at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 32 and 48 hours (h) post [14C]-AZD2014 dose in the Single Dose Period.

Population: The Pharmacokinetic (PK) analysis population consisted of all evaluable patients who were dosed with \[14C\]-AZD2014 in Cycle 0 and who had reportable and evaluable PK concentration data. Patients were excluded if they vomited at or before 3 hours post-dosing or had identified procedural or scientific deficiency as being likely to impact the PK data.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Total Radioactivity in Plasma Following Administration of [14C]-AZD2014	0.5 h (n = 3)	4013 nanogram equivalent/millilitre (ngEq/mL)	Geometric Coefficient of Variation 41.55
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Total Radioactivity in Plasma Following Administration of [14C]-AZD2014	1 h (n = 4)	3415 nanogram equivalent/millilitre (ngEq/mL)	Geometric Coefficient of Variation 40.69
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Total Radioactivity in Plasma Following Administration of [14C]-AZD2014	1.5 h (n = 4)	2901 nanogram equivalent/millilitre (ngEq/mL)	Geometric Coefficient of Variation 34.87
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Total Radioactivity in Plasma Following Administration of [14C]-AZD2014	2 h (n = 4)	2693 nanogram equivalent/millilitre (ngEq/mL)	Geometric Coefficient of Variation 36.75
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Total Radioactivity in Plasma Following Administration of [14C]-AZD2014	3 h (n = 4)	2105 nanogram equivalent/millilitre (ngEq/mL)	Geometric Coefficient of Variation 38.82
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Total Radioactivity in Plasma Following Administration of [14C]-AZD2014	4 h (n = 4)	1818 nanogram equivalent/millilitre (ngEq/mL)	Geometric Coefficient of Variation 37.85
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Total Radioactivity in Plasma Following Administration of [14C]-AZD2014	6 h (n = 4)	1419 nanogram equivalent/millilitre (ngEq/mL)	Geometric Coefficient of Variation 37.31
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Total Radioactivity in Plasma Following Administration of [14C]-AZD2014	8 h (n = 4)	914.1 nanogram equivalent/millilitre (ngEq/mL)	Geometric Coefficient of Variation 42.85
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Total Radioactivity in Plasma Following Administration of [14C]-AZD2014	12 h (n = 4)	478.6 nanogram equivalent/millilitre (ngEq/mL)	Geometric Coefficient of Variation 47.42
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Total Radioactivity in Plasma Following Administration of [14C]-AZD2014	24 h (n = 4)	97.16 nanogram equivalent/millilitre (ngEq/mL)	Geometric Coefficient of Variation 35.55
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Total Radioactivity in Plasma Following Administration of [14C]-AZD2014	32 h (n = 4)	45.68 nanogram equivalent/millilitre (ngEq/mL)	Geometric Coefficient of Variation 35.92
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Total Radioactivity in Plasma Following Administration of [14C]-AZD2014	48 h (n = 3)	27.21 nanogram equivalent/millilitre (ngEq/mL)	Geometric Coefficient of Variation 43.22

Secondary

Best Overall Response (BOR) Assessment

Anti-tumour activity through assessment of BOR. BOR was defined for each patient as follows according to the RECIST 1.1 criteria: Complete Response (CR): Disappearance of all target lesions since baseline. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions. Stable Disease (SD): Any cases that do not qualify for either PR or progressive disease (PD). PD: At least a 20% increase in the sum of the diameters of target lesions. BOR for each patient was determined as the best response recorded from the day study treatment started until progression or until the last evaluable RECIST tumour assessment in the absence of progression.

Time frame: RECIST 1.1 assessments were performed pre-dose at screening and then once every 8 weeks relative to the start of treatment in the Multiple Dose Period.

Population: The efficacy analysis population consisted of all patients who received at least one dose of study treatment and had a baseline tumour assessment.

Arm	Measure	Group	Value (NUMBER)
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Best Overall Response (BOR) Assessment	Non-response: Not evaluable	0 Participants
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Best Overall Response (BOR) Assessment	Response: CR	0 Participants
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Best Overall Response (BOR) Assessment	Response: PR	0 Participants
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Best Overall Response (BOR) Assessment	Non-response: SD	3 Participants
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Best Overall Response (BOR) Assessment	Non-response: Progression	0 Participants
[14C]-AZD2014 Then AZD2014 + Fulvestrant	Best Overall Response (BOR) Assessment	Non-response: Progression	1 Participants
[14C]-AZD2014 Then AZD2014 + Fulvestrant	Best Overall Response (BOR) Assessment	Non-response: SD	0 Participants
[14C]-AZD2014 Then AZD2014 + Fulvestrant	Best Overall Response (BOR) Assessment	Response: CR	0 Participants
[14C]-AZD2014 Then AZD2014 + Fulvestrant	Best Overall Response (BOR) Assessment	Non-response: Not evaluable	0 Participants
[14C]-AZD2014 Then AZD2014 + Fulvestrant	Best Overall Response (BOR) Assessment	Response: PR	0 Participants

Secondary

Best Percentage Change in Tumour Size From Baseline

Assessment of anti-tumour activity through measurement of tumour lesions. Tumour size was defined as the sum of the lengths of the longest diameters of the RECIST 1.1 target lesions.

Time frame: RECIST 1.1 assessments were performed pre-dose at screening and then once every 8 weeks relative to the start of treatment in the Multiple Dose Period.

Population: The efficacy analysis population consisted of all patients who received at least one dose of study treatment and had a baseline tumour assessment. Patients with available data are presented.

Arm	Measure	Value (MEDIAN)
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Best Percentage Change in Tumour Size From Baseline	-8.75 Percentage change in tumour size
[14C]-AZD2014 Then AZD2014 + Fulvestrant	Best Percentage Change in Tumour Size From Baseline	3.1 Percentage change in tumour size

Secondary

Number of AEs Experienced by Patients.

AEs (including serious AEs \[SAEs\]) were collected from the time of informed consent (Visit 1) and throughout the study, including the 30-day follow-up. The numbers of patients experiencing any AEs and SAEs, causally related AEs and SAEs, and SAEs which were fatal are presented.

Time frame: From Day 1 of the Single Dose Period to 30 days after the last dose of AZD2014 administered in the Multiple Dose Period.

Population: The safety analysis population consisted of all patients who received at least one dose of AZD2014 (radiolabelled or non-radiolabelled).

Arm	Measure	Group	Value (NUMBER)
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Number of AEs Experienced by Patients.	Patients who experienced any AE	3 Participants
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Number of AEs Experienced by Patients.	Patients who experienced any SAE	1 Participants
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Number of AEs Experienced by Patients.	Patients who experienced any causally related SAE	0 Participants
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Number of AEs Experienced by Patients.	Patients who experienced fatal SAE	0 Participants
[14C]-AZD2014 (Period 1 [Day 1 - 8])	Number of AEs Experienced by Patients.	Patients who experienced any causally related AE	3 Participants
[14C]-AZD2014 Then AZD2014 + Fulvestrant	Number of AEs Experienced by Patients.	Patients who experienced fatal SAE	0 Participants
[14C]-AZD2014 Then AZD2014 + Fulvestrant	Number of AEs Experienced by Patients.	Patients who experienced any AE	1 Participants
[14C]-AZD2014 Then AZD2014 + Fulvestrant	Number of AEs Experienced by Patients.	Patients who experienced any causally related AE	1 Participants
[14C]-AZD2014 Then AZD2014 + Fulvestrant	Number of AEs Experienced by Patients.	Patients who experienced any causally related SAE	0 Participants
[14C]-AZD2014 Then AZD2014 + Fulvestrant	Number of AEs Experienced by Patients.	Patients who experienced any SAE	1 Participants

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026

Absorption, Metabolism, Excretion and Pharmacokinetics of a Single Dose [14C]AZD2014 Followed by a Multiple Dose Phase

Conditions

Keywords

Brief summary

Detailed description

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Recruitment details

Pre-assignment details

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Apparent Total Body Clearance (CL/F) of AZD2014

Apparent Volume of Distribution at Steady State (Vss/F) for AZD2014 in Plasma

Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC[0-t]) for AZD2014 in Plasma and Saliva

Area Under the Plasma Concentration-time Curve (AUC) for AZD2014

AZD2014 Concentrations in Plasma Following Administration of [14C]-AZD2014

AZD2014 Concentrations in Saliva Following Administration of [14C]-AZD2014

Cmax for Total [14C] Radioactivity in Whole Blood and Saliva

Cumulative Percentage of [14C]-AZD2014 Recovered by Day 8

Cumulative Percentage of Total [14C] Radioactivity Excreted in Stool as a Percentage of the Dose (fe Cum%[f])

Cumulative Percentage of Total [14C] Radioactivity Excreted in Urine as a Percentage of the Dose (fe Cum%[R])

Fraction of AZD2014 Excreted in Urine as a Percentage of the Dose (fe%[R])

Half-life Associated With Terminal Slope (lambda_z) of a Semi-logarithmic Concentration-time Curve (t1/2[lambda_z]) for AZD2014 in Plasma

Maximum Observed Concentration (Cmax) of AZD2014 in Plasma and Saliva

Mean Residence Time (MRT) of AZD2014

Ratio of AZD2014 Concentration to Total Radioactivity Concentration in Saliva

Ratio of Whole Blood Total Radioactivity to Plasma Total Radioactivity

Renal Clearance (CL[R]) of AZD2014 From Plasma.

Terminal Elimination Rate Constant (lambda_z) for AZD2014 in Plasma

Time to Last Measurable Concentration (t[Last]) for AZD2014 in Plasma and Saliva

Time to Maximum Observed Concentration (Tmax) for AZD2014 in Plasma and Saliva

T(Last) for [14C] Radioactivity in Whole Blood and Saliva

Tmax for [14C] Radioactivity in Whole Blood and Saliva

Total Radioactivity Concentrations in Blood Following Administration of [14C]-AZD2014

Total Radioactivity Concentrations in Saliva Following Administration of [14C]-AZD2014

Total Radioactivity in Plasma Following Administration of [14C]-AZD2014

Best Overall Response (BOR) Assessment

Best Percentage Change in Tumour Size From Baseline

Number of AEs Experienced by Patients.