Advanced Malignancies
Conditions
Keywords
Safety,, Pharmacokinetics,, Pegylated liposomal doxorubicin,, Dose finding
Brief summary
This is a modular Phase I/IIa, open-label, multi-centre, study of AZD7648 administered orally, either as a monotherapy, or in combination with either cytotoxic chemotherapies or novel anti-cancer agents in participants with advanced malignancies.
Detailed description
The modular design allows for an escalation of the dose of AZD7648 alone or in combination with either cytotoxic chemotherapies or novel anti-cancer agents, with intensive safety monitoring to ensure the safety of the participants. The study consists of 2 modules each evaluating the safety and tolerability of AZD7648 monotherapy or with a specific combination partner. Core module of the study is dose escalation (Part A) of AZD7648 monotherapy, administered orally, in participants with advanced solid tumours. Combination module 1 has 2 study parts: Part A consisting of dose escalation cohorts and Part B, a safety and proof of concept Phase IIa expansion. A Safety Review Committee will review evaluable participants at each cohort and assess if the study should progress to Part B.
Interventions
DRUGAZD7648
Core: AZD7648 will be administered orally
DRUGPLD
The starting dose of PLD is 40 mg/m\^2, administered by intravenous infusion once every 4 weeks, for a maximum of 6 cycles
Sponsors
Parexel
AstraZeneca
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Masking description
This is an open-label study; there will be no blinding.
Eligibility
Sex/Gender
ALL
Age
18 Years to 130 Years
Healthy volunteers
No
Inclusion criteria
1. Capable and willing to give signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF). 2. Participant must be at least 18 years of age, at the time of signing the ICF. 3. Participants must have histological or cytological confirmation of advanced malignancy considered to be suitable for study treatment. 4. Eastern cooperative oncology group performance status 0-1. 5. Life expectancy greater than 12 weeks. 6. Progressive cancer at the time of study entry. 7. Pharmacodynamics expansion cohorts: Participants must have at least 1 tumour suitable for biopsy and consent to having biopsies collected. 8. Negative pregnancy test (urine or serum) prior to start of dosing for women of childbearing potential. 9. Female participants must be post-menopausal, surgically sterile, or using an acceptable method of contraception for the duration of the study (from the time they sign consent) and for 12 weeks after the last dose of study treatment to prevent pregnancy. 10. For the duration of the study (from the time they sign consent) and for 12 weeks after the last dose of study treatment, sexually active male participants must be willing to use contraception. Post-menopausal is defined as: * No menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the post-menopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy). However in the absence of 12 months of amenorrhea, a FSH measurement is insufficient. * Radiation-induced oophorectomy with last menses greater than 12 months ago. * Chemotherapy-induced menopause with greater than 12 month interval since last menses. * Surgical sterilisation.
Exclusion criteria
1. Any unresolved toxicities from prior therapy common terminology criteria for adverse event (CTCAE) Grade ≥2 (with the exception of alopecia). 2. Spinal cord compression or brain metastases unless definitively treated, asymptomatic, stable and not requiring steroids for at least 4 weeks. 3. As judged by the Investigator, any evidence of severe or uncontrolled medical conditions including but not limited to: • Uncontrolled diabetes mellitus, uncontrolled seizures, active infection requiring systemic antibiotics, antifungal or antiviral drugs, severe chronic obstructive pulmonary disease, severe Parkinson's disease, active inflammatory bowel disease, psychiatric condition, active bleeding diatheses, renal transplant, or active infection including any participant with active hepatitis B, hepatitis C or human immunodeficiency virus. 4. Any other malignancy which has been active or treated within the past 3 years, with the exception of in situ cancer of the cervix, non-melanoma skin cancer, ductal carcinoma in situ, Stage 1 Grade 1 endometrial carcinoma, or other solid tumours including lymphomas curatively treated with no evidence of disease for ≥5 years. 5. Refractory nausea and vomiting or unable to swallow and retain oral medication, chronic gastrointestinal diseases or previous bowel resection with clinically significant sequelae that would preclude adequate absorption of AZD7648, gastrointestinal symptoms CTCAE Grade \>1, history of gastrointestinal ulceration and gastrointestinal haemorrhage within 6 months of first study drug administration. 6 Receiving or having received anti-cancer treatment within the following periods prior to the first dose of investigational product: (a) Cytotoxic treatment: 3 weeks, (b) Non-cytotoxic drugs: including small molecule investigational products: 3 weeks or 5 half-lives (whichever is longest), (c) Biological products including investigational immuno-oncology agents: 4 weeks, (d) Radiation with a limited field for palliation: 1 week (3 months for radiation to the abdomen or pelvis), (e) Radiation to \>30% of the bone marrow or with a wide field: 4 weeks, (f) Lung radiation: 60 days, (g) Major surgery: 4 weeks; minor surgery or biopsy: 1 week 7. During the 4 weeks prior to the first dose, receiving corticosteroids at a dose of \>10 mg prednisone/day or equivalent for any reason. Ongoing low dose steroids for longer than 3 months (excluding inhalational, nasal, creams, lotions, and gels) are not allowed. 8\. Receiving or having received concomitant medications, herbal supplements and/or foods known to significantly modulate CYP3A4 activity. 9\. Prior exposure to a deoxyribonucleic acid-pharmacokinetics inhibitor or hypersensitivity to any excipient of the product. 10\. Cardiac dysfunction as defined by any of the following within 6 months of study entry: (a) Acute myocardial infarction, (b) New York Heart Association Class II/III/IV heart failure, (c) Unstable angina, (d) Unstable cardiac arrhythmias 11. Any of the following cardiac criteria: (a) Known reduced left ventricular ejection fraction below the institutional lower limit of normal, (b) Mean resting corrected QT interval (QTc) \>470 milliseconds obtained from 3 electrocardiograms in 24 hours using the Fridericia formula, (c) Any factors that increase the risk of QTc prolongation or arrhythmic events such as hypokalaemia, congenital long QT syndrome, immediate family history of long QT syndrome or unexplained sudden death under 40 years of age 12. Inadequate hematological or organ function 13. Involvement in the planning and/or conduct of the study. 14. Judgement by the Investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions and requirements. 15\. Previous enrolment in the present study. 16. For female participant only: currently pregnant or breast-feeding. 17. For food effect cohort only: insulin dependent diabetes. 18. History and/or presence of coronavirus disease 2019.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Adverse Events or Serious Adverse Events | From Screening (Day -28) till study drug discontinuation (3.2 years) | Safety and tolerability of AZD7648 when given orally to patients with advanced malignancies, as monotherapy and in combination with anti-cancer agents was assessed. |
| Number of Patients With Dose Limiting Toxicities (DLTs) | From Screening (Day -28) till study drug discontinuation (3.2 years) | A DLT is defined as an AE that occurs from the first dose of study treatment up to and including Cycle 1, Day 28 (the DLT assessment period) that is assessed as unrelated to the disease, intercurrent illness, or concomitant medications. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under Plasma Concentration-time Curve in the Dosing Interval τ (AUCτ) | Monotherapy and Combination therapy: Cycle 0 Day 1 Pre-dose to 72 hours post-dose (each cycle is 28 days) | The AUCτ of AZD7648, at steady state after multiple dosing, when given orally as monotherapy and in combination with anti-cancer agents. |
| Maximum Observed Plasma (Peak) Drug Concentration After Single Dose and Multiple Doses (Cmax) | Monotherapy: Cycle 0 Day 1 Pre-dose to 72 hours post-dose, Cycle 1 Day 8 Pre-dose to 12 hours post dose; Combination therapy: Cycle 0 Day 1 Pre-dose to 12 hours post dose and Cycle 1 Days 7, 8 Pre-dose to 8 hours post dose (each cycle is 28 days) | The Cmax of AZD7648, following a single dose and at steady state after multiple dosing, when given orally as monotherapy and in combination with anti-cancer agents. |
| Time to Reach Maximum Plasma Concentration (Tmax) | Monotherapy: Cycle 0 Day 1 Pre-dose to 72 hours post-dose, Cycle 1 Day 8 Pre-dose to 12 hours post dose; Combination therapy: Cycle 0 Day 1 Pre-dose to 12 hours post dose and Cycle 1 Days 7, 8 Pre-dose to 8 hours post dose (each cycle is 28 days) | The tmax of AZD7648, following a single dose and at steady state after multiple dosing, when given orally as monotherapy and in combination with anti-cancer agents. |
| Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t½λz) | Monotherapy and Combination therapy: Cycle 0 Day 1 Pre-dose to 72 hours post-dose (each cycle is 28 days) | The t½λ of AZD7648, following a single dose and at steady state after multiple dosing, when given orally as monotherapy and in combination with anti-cancer agents. |
| Accumulation Ratio for Area Under Curve (Rac AUC) | Monotherapy: Cycle 1 Day 8 Pre-dose to 12 hours post dose; Combination therapy: Cycle 1 Days 7 and 8 Pre-dose to 8 hours post dose (each cycle is 28 days) | The Rac AUC of AZD7648, following a single dose and at steady state after multiple dosing, when given orally as monotherapy and in combination with anti-cancer agents. Accumulation ratio for AUC, calculated by multiple dose AUCτ/single dose AUC(0-12) or AUC(0-24). |
| Area Under Plasma Concentration-time Curve From Zero to Infinity (AUCinf) | Monotherapy and Combination therapy: Cycle 0 Day 1 Pre-dose to 72 hours post-dose [each cycle is 28 days] | The AUCinf of AZD7648, following a single dose and at steady state after multiple dosing, when given orally as monotherapy and in combination with anti-cancer agents. |
| Dose Proportionality (TCP) | Monotherapy: Cycle 1 Day 8 Pre-dose to 12 hours post dose; Combination therapy: Cycle 1 Days 7 and 8 Pre-dose to 8 hours post dose (each cycle is 28 days) | The TCP of AZD7648, following a single dose and at steady state after multiple dosing, when given orally as monotherapy and in combination with anti-cancer agents. Temporal change parameter in systemic exposure, calculated as multiple dose AUCtau/single dose AUCinf. |
| Objective Response Rate (ORR) | First dose of study treatment on Cycle 1 Day 1 (each cycle is 28 days) until progression or the last evaluable assessment in the absence of progression (3.2 years) | ORR is defined as the percentage of patients who have a confirmed visit response of complete response (CR) or partial response (PR) prior to any evidence of progression (as defined by Response Evaluation Criteria in Solid Tumours 1.1). CR is defined when all target lesions (TLs) and non-target lesions (NTLs) present at baseline have disappeared (with the exception of lymph nodes which must be \<10mm to be considered non pathological) and no new lesions have developed since baseline. PR is defined when the sum of diameters of the TLs has decreased by 30% or more compared to baseline (with no evidence of progression) and the NTLs are at least stable with no evidence of new lesions. |
| Progression Free Survival (PFS) for Monotherapy | At 12 months | PFS is defined as the time from first dose of Cycle 1 until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from study therapy or receives another anti-cancer therapy prior to progression. Disease progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as increased by \> 20% or more compared to the smallest sum of diameters on study. |
| Progression Free Survival (PFS) for Combination Therapy | At 18 months | PFS is defined as the time from first dose of Cycle 1 until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from study therapy or receives another anti-cancer therapy prior to progression. Disease progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as increased by \> 20% or more compared to the smallest sum of diameters on study. |
| Accumulation Ratio for Cmax (Rac Cmax) | Monotherapy: Cycle 1 Day 8 Pre-dose to 12 hours post dose; Combination therapy: Cycle 1 Days 7 and 8 Pre-dose to 8 hours post dose (each cycle is 28 days) | The Rac Cmax of AZD7648, following a single dose and at steady state after multiple dosing, when given orally as monotherapy and in combination with anti-cancer agents. Accumulation ratio for Cmax, calculated by multiple dose Cmax/single dose Cmax. |
| Area Under the Plasma Concentration-curve From Zero to the Last Quantifiable Concentration (AUClast) | Monotherapy and Combination therapy: Cycle 0 Day 1 Pre-dose to 72 hours post-dose (each cycle is 28 days) | The AUClast of AZD7648, following a single dose, when given orally as monotherapy and in combination with anti-cancer agents. |
Countries
United Kingdom, United States
Participant flow
Recruitment details
A total of 30 patients were enrolled at two sites in the United States and three sites in the United Kingdom from 09 October 2019 to 07 December 2022.
Pre-assignment details
Patients who met the inclusion and none of the exclusion criteria were enrolled to the study. This study consisted of a screening period of 28 days. All the study assessments were performed as per schedule of assessment.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: AZD7648 Dose A (Monotherapy) Patients received single dose A of AZD7648, and after a washout period patients received multiple continuous dosing of dose A of AZD7648 in 28-day cycle regimen orally on an empty stomach. | 1 |
| Cohort 2: AZD7648 Dose A1 (Monotherapy) Patients received single dose A1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose A of AZD7648 in 28-day cycle regimen orally on an empty stomach. | 1 |
| Cohort 3: AZD7648 Dose B1 (Monotherapy) Patients received single dose B1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose B1 of AZD7648 in 28-day cycle regimen orally on an empty stomach. | 1 |
| Cohort 4: AZD7648 Dose C1 (Monotherapy) Patients received single dose C1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose C1 of AZD7648 in 28-day cycle regimen orally on an empty stomach. | 1 |
| Cohort 5: AZD7648 Dose D1 (Monotherapy) Patients received single dose D1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose D1 of AZD7648 in 28-day cycle regimen orally on an empty stomach. | 3 |
| Cohort 6: AZD7648 Dose E1 (Monotherapy) Patients received single dose E1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose E1 of AZD7648 in 28-day cycle regimen orally on an empty stomach. | 4 |
| Cohort 7: AZD7648 Dose F1 (Monotherapy) Patients received single dose F1 of AZD7648, and after a washout period patients received multiple continuous dosing of dose F1 of AZD7648 in 28-day cycle regimen orally on an empty stomach. | 3 |
| Cohort 1: AZD7648 Dose C1 + PLD (Combination Therapy) Patients received continuous dosing of dose C1 of AZD7648 orally on an empty stomach. In combination of AZD7648 patients also received PLD of 40 mg/m\^2, administered by intravenous (IV) infusion once every 4 weeks. | 2 |
| Cohort 1: AZD7648 Dose C + PLD (Combination Therapy) Patients received single dosing of dose C of AZD7648 orally on an empty stomach. In combination of AZD7648 patients also received PLD of 40 mg/m\^2, administered by IV infusion once every 4 weeks. | 2 |
| Cohort 2: AZD7648 Dose C2 + PLD (Combination Therapy) Patients received single dosing of dose C2 of AZD7648 orally on an empty stomach. In combination of AZD7648 patients also received PLD of 40 mg/m\^2, administered by IV infusion once every 4 weeks. | 5 |
| Cohort 3: AZD7648 Dose X + PLD (Combination Therapy) Patients received single dosing of dose X of AZD7648 orally on an empty stomach. In combination of AZD7648 patients also received PLD of 40 mg/m\^2, administered by IV infusion once every 4 weeks. | 7 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Combination Therapy Part A | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 |
| Combination Therapy Part A | Death | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 |
| Combination Therapy Part A | Other than specified main reasons | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Combination Therapy Part A | Physician Decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 |
| Combination Therapy Part A | Progressive disease | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 2 | 3 |
| Combination Therapy Part A | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Monotherapy Part A | Death | 0 | 0 | 1 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Monotherapy Part A | Progressive Disease | 0 | 1 | 0 | 0 | 0 | 1 | 2 | 0 | 0 | 0 | 0 |
| Monotherapy Part A | Withdrawal by Subject | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Cohort 1: AZD7648 Dose A (Monotherapy) | Cohort 2: AZD7648 Dose A1 (Monotherapy) | Cohort 3: AZD7648 Dose B1 (Monotherapy) | Cohort 4: AZD7648 Dose C1 (Monotherapy) | Cohort 5: AZD7648 Dose D1 (Monotherapy) | Cohort 6: AZD7648 Dose E1 (Monotherapy) | Cohort 7: AZD7648 Dose F1 (Monotherapy) | Cohort 1: AZD7648 Dose C1 + PLD (Combination Therapy) | Cohort 1: AZD7648 Dose C + PLD (Combination Therapy) | Cohort 2: AZD7648 Dose C2 + PLD (Combination Therapy) | Cohort 3: AZD7648 Dose X + PLD (Combination Therapy) | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | NA Years | NA Years | NA Years | NA Years | 64.3 Years STANDARD_DEVIATION 6.35 | 60.3 Years STANDARD_DEVIATION 8.18 | 51.3 Years STANDARD_DEVIATION 2.08 | NA Years | NA Years | 56.6 Years STANDARD_DEVIATION 10.16 | 61.7 Years STANDARD_DEVIATION 16.18 | 60.20 Years STANDARD_DEVIATION 10.2 |
| Race/Ethnicity, Customized Race Other | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 3 Participants | 2 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 14 Participants |
| Race/Ethnicity, Customized Race White | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 2 Participants | 2 Participants | 5 Participants | 5 Participants | 16 Participants |
| Sex/Gender, Customized All | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 2 Participants | 2 Participants | 0 Participants | 1 Participants | 11 Participants |
| Sex/Gender, Customized Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 3 Participants | 0 Participants | 0 Participants | 3 Participants | 6 Participants | 15 Participants |
| Sex/Gender, Customized Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 4 Participants |
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 | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 1 | 1 / 1 | 1 / 1 | 1 / 3 | 1 / 4 | 0 / 3 | 0 / 2 | 1 / 2 | 0 / 5 | 1 / 7 |
| other Total, other adverse events | 0 / 1 | 1 / 1 | 1 / 1 | 1 / 1 | 2 / 3 | 4 / 4 | 3 / 3 | 2 / 2 | 2 / 2 | 4 / 5 | 7 / 7 |
| serious Total, serious adverse events | 0 / 1 | 0 / 1 | 0 / 1 | 0 / 1 | 1 / 3 | 4 / 4 | 0 / 3 | 1 / 2 | 1 / 2 | 0 / 5 | 4 / 7 |
Outcome results
Primary
Number of Patients With Adverse Events or Serious Adverse Events
Safety and tolerability of AZD7648 when given orally to patients with advanced malignancies, as monotherapy and in combination with anti-cancer agents was assessed.
Time frame: From Screening (Day -28) till study drug discontinuation (3.2 years)
Population: All patients who received at least 1 dose of any study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1: AZD7648 Dose A (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE leading to AZD7648 dose modification | 0 Participants |
| Cohort 1: AZD7648 Dose A (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE, possibly related to AZD7648 | 0 Participants |
| Cohort 1: AZD7648 Dose A (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE causing discontinuation of AZD7648 | 0 Participants |
| Cohort 1: AZD7648 Dose A (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE leading to AZD7648 dose reduction | 0 Participants |
| Cohort 1: AZD7648 Dose A (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE with outcome of death | 0 Participants |
| Cohort 1: AZD7648 Dose A (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE | 0 Participants |
| Cohort 1: AZD7648 Dose A (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE with outcome of death, possibly related to AZD7648 | 0 Participants |
| Cohort 1: AZD7648 Dose A (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE of CTCAE Grade 3 or higher | 0 Participants |
| Cohort 1: AZD7648 Dose A (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE leading to discontinuation of AZD7648 | 0 Participants |
| Cohort 1: AZD7648 Dose A (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE with outcome of death, possibly related to AZD7648 | 0 Participants |
| Cohort 1: AZD7648 Dose A (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE | 0 Participants |
| Cohort 1: AZD7648 Dose A (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE leading to AZD7648 dose interruption | 0 Participants |
| Cohort 1: AZD7648 Dose A (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE of CTCAE Grade 3 or higher, possibly related to AZD7648 | 0 Participants |
| Cohort 1: AZD7648 Dose A (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE causing discontinuation of AZD7648, possibly related to AZD7648 | 0 Participants |
| Cohort 1: AZD7648 Dose A (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE possibly related to AZD7648 | 0 Participants |
| Cohort 1: AZD7648 Dose A (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE with outcome of death | 0 Participants |
| Cohort 2: AZD7648 Dose A1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE possibly related to AZD7648 | 0 Participants |
| Cohort 2: AZD7648 Dose A1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE of CTCAE Grade 3 or higher | 0 Participants |
| Cohort 2: AZD7648 Dose A1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE leading to AZD7648 dose interruption | 0 Participants |
| Cohort 2: AZD7648 Dose A1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE with outcome of death | 0 Participants |
| Cohort 2: AZD7648 Dose A1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE, possibly related to AZD7648 | 0 Participants |
| Cohort 2: AZD7648 Dose A1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE with outcome of death, possibly related to AZD7648 | 0 Participants |
| Cohort 2: AZD7648 Dose A1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE causing discontinuation of AZD7648 | 0 Participants |
| Cohort 2: AZD7648 Dose A1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE causing discontinuation of AZD7648, possibly related to AZD7648 | 0 Participants |
| Cohort 2: AZD7648 Dose A1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE leading to AZD7648 dose modification | 0 Participants |
| Cohort 2: AZD7648 Dose A1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE with outcome of death, possibly related to AZD7648 | 0 Participants |
| Cohort 2: AZD7648 Dose A1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE | 1 Participants |
| Cohort 2: AZD7648 Dose A1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE of CTCAE Grade 3 or higher, possibly related to AZD7648 | 0 Participants |
| Cohort 2: AZD7648 Dose A1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE | 0 Participants |
| Cohort 2: AZD7648 Dose A1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE leading to AZD7648 dose reduction | 0 Participants |
| Cohort 2: AZD7648 Dose A1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE leading to discontinuation of AZD7648 | 0 Participants |
| Cohort 2: AZD7648 Dose A1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE with outcome of death | 0 Participants |
| Cohort 3: AZD7648 Dose B1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE of CTCAE Grade 3 or higher, possibly related to AZD7648 | 0 Participants |
| Cohort 3: AZD7648 Dose B1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE causing discontinuation of AZD7648 | 0 Participants |
| Cohort 3: AZD7648 Dose B1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE with outcome of death | 0 Participants |
| Cohort 3: AZD7648 Dose B1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE leading to AZD7648 dose reduction | 0 Participants |
| Cohort 3: AZD7648 Dose B1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE with outcome of death, possibly related to AZD7648 | 0 Participants |
| Cohort 3: AZD7648 Dose B1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE with outcome of death, possibly related to AZD7648 | 0 Participants |
| Cohort 3: AZD7648 Dose B1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE | 1 Participants |
| Cohort 3: AZD7648 Dose B1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE | 0 Participants |
| Cohort 3: AZD7648 Dose B1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE leading to AZD7648 dose modification | 0 Participants |
| Cohort 3: AZD7648 Dose B1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE of CTCAE Grade 3 or higher | 0 Participants |
| Cohort 3: AZD7648 Dose B1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE leading to AZD7648 dose interruption | 0 Participants |
| Cohort 3: AZD7648 Dose B1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE possibly related to AZD7648 | 0 Participants |
| Cohort 3: AZD7648 Dose B1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE with outcome of death | 0 Participants |
| Cohort 3: AZD7648 Dose B1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE, possibly related to AZD7648 | 0 Participants |
| Cohort 3: AZD7648 Dose B1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE leading to discontinuation of AZD7648 | 0 Participants |
| Cohort 3: AZD7648 Dose B1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE causing discontinuation of AZD7648, possibly related to AZD7648 | 0 Participants |
| Cohort 4: AZD7648 Dose C1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE with outcome of death, possibly related to AZD7648 | 0 Participants |
| Cohort 4: AZD7648 Dose C1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE possibly related to AZD7648 | 0 Participants |
| Cohort 4: AZD7648 Dose C1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE with outcome of death, possibly related to AZD7648 | 0 Participants |
| Cohort 4: AZD7648 Dose C1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE causing discontinuation of AZD7648, possibly related to AZD7648 | 0 Participants |
| Cohort 4: AZD7648 Dose C1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE leading to AZD7648 dose reduction | 0 Participants |
| Cohort 4: AZD7648 Dose C1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE leading to AZD7648 dose interruption | 0 Participants |
| Cohort 4: AZD7648 Dose C1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE | 0 Participants |
| Cohort 4: AZD7648 Dose C1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE causing discontinuation of AZD7648 | 0 Participants |
| Cohort 4: AZD7648 Dose C1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE of CTCAE Grade 3 or higher, possibly related to AZD7648 | 0 Participants |
| Cohort 4: AZD7648 Dose C1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE leading to discontinuation of AZD7648 | 0 Participants |
| Cohort 4: AZD7648 Dose C1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE | 1 Participants |
| Cohort 4: AZD7648 Dose C1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE with outcome of death | 0 Participants |
| Cohort 4: AZD7648 Dose C1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE leading to AZD7648 dose modification | 0 Participants |
| Cohort 4: AZD7648 Dose C1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE of CTCAE Grade 3 or higher | 0 Participants |
| Cohort 4: AZD7648 Dose C1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE, possibly related to AZD7648 | 0 Participants |
| Cohort 4: AZD7648 Dose C1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE with outcome of death | 0 Participants |
| Cohort 5: AZD7648 Dose D1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE | 1 Participants |
| Cohort 5: AZD7648 Dose D1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE, possibly related to AZD7648 | 0 Participants |
| Cohort 5: AZD7648 Dose D1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE leading to AZD7648 dose modification | 1 Participants |
| Cohort 5: AZD7648 Dose D1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE | 2 Participants |
| Cohort 5: AZD7648 Dose D1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE leading to AZD7648 dose interruption | 1 Participants |
| Cohort 5: AZD7648 Dose D1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE possibly related to AZD7648 | 1 Participants |
| Cohort 5: AZD7648 Dose D1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE leading to AZD7648 dose reduction | 0 Participants |
| Cohort 5: AZD7648 Dose D1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE leading to discontinuation of AZD7648 | 0 Participants |
| Cohort 5: AZD7648 Dose D1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE of CTCAE Grade 3 or higher | 2 Participants |
| Cohort 5: AZD7648 Dose D1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE causing discontinuation of AZD7648, possibly related to AZD7648 | 0 Participants |
| Cohort 5: AZD7648 Dose D1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE of CTCAE Grade 3 or higher, possibly related to AZD7648 | 0 Participants |
| Cohort 5: AZD7648 Dose D1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE causing discontinuation of AZD7648 | 0 Participants |
| Cohort 5: AZD7648 Dose D1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE with outcome of death | 0 Participants |
| Cohort 5: AZD7648 Dose D1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE with outcome of death, possibly related to AZD7648 | 0 Participants |
| Cohort 5: AZD7648 Dose D1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE with outcome of death, possibly related to AZD7648 | 0 Participants |
| Cohort 5: AZD7648 Dose D1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE with outcome of death | 0 Participants |
| Cohort 6: AZD7648 Dose E1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE, possibly related to AZD7648 | 1 Participants |
| Cohort 6: AZD7648 Dose E1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE with outcome of death, possibly related to AZD7648 | 0 Participants |
| Cohort 6: AZD7648 Dose E1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE with outcome of death | 1 Participants |
| Cohort 6: AZD7648 Dose E1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE of CTCAE Grade 3 or higher, possibly related to AZD7648 | 2 Participants |
| Cohort 6: AZD7648 Dose E1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE causing discontinuation of AZD7648, possibly related to AZD7648 | 1 Participants |
| Cohort 6: AZD7648 Dose E1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE with outcome of death | 1 Participants |
| Cohort 6: AZD7648 Dose E1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE | 4 Participants |
| Cohort 6: AZD7648 Dose E1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE of CTCAE Grade 3 or higher | 4 Participants |
| Cohort 6: AZD7648 Dose E1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE leading to discontinuation of AZD7648 | 3 Participants |
| Cohort 6: AZD7648 Dose E1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE leading to AZD7648 dose reduction | 1 Participants |
| Cohort 6: AZD7648 Dose E1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE possibly related to AZD7648 | 2 Participants |
| Cohort 6: AZD7648 Dose E1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE leading to AZD7648 dose interruption | 3 Participants |
| Cohort 6: AZD7648 Dose E1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE | 4 Participants |
| Cohort 6: AZD7648 Dose E1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE leading to AZD7648 dose modification | 3 Participants |
| Cohort 6: AZD7648 Dose E1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE with outcome of death, possibly related to AZD7648 | 0 Participants |
| Cohort 6: AZD7648 Dose E1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE causing discontinuation of AZD7648 | 3 Participants |
| Cohort 7: AZD7648 Dose F1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE, possibly related to AZD7648 | 0 Participants |
| Cohort 7: AZD7648 Dose F1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE leading to AZD7648 dose modification | 2 Participants |
| Cohort 7: AZD7648 Dose F1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE | 3 Participants |
| Cohort 7: AZD7648 Dose F1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE possibly related to AZD7648 | 2 Participants |
| Cohort 7: AZD7648 Dose F1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE of CTCAE Grade 3 or higher | 2 Participants |
| Cohort 7: AZD7648 Dose F1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE of CTCAE Grade 3 or higher, possibly related to AZD7648 | 2 Participants |
| Cohort 7: AZD7648 Dose F1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE with outcome of death | 0 Participants |
| Cohort 7: AZD7648 Dose F1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE with outcome of death, possibly related to AZD7648 | 0 Participants |
| Cohort 7: AZD7648 Dose F1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE | 0 Participants |
| Cohort 7: AZD7648 Dose F1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE with outcome of death | 0 Participants |
| Cohort 7: AZD7648 Dose F1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE with outcome of death, possibly related to AZD7648 | 0 Participants |
| Cohort 7: AZD7648 Dose F1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE causing discontinuation of AZD7648 | 0 Participants |
| Cohort 7: AZD7648 Dose F1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE causing discontinuation of AZD7648, possibly related to AZD7648 | 0 Participants |
| Cohort 7: AZD7648 Dose F1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE leading to discontinuation of AZD7648 | 0 Participants |
| Cohort 7: AZD7648 Dose F1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE leading to AZD7648 dose reduction | 1 Participants |
| Cohort 7: AZD7648 Dose F1 (Monotherapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE leading to AZD7648 dose interruption | 2 Participants |
| Cohort 1: AZD7648 Dose C1 + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE with outcome of death, possibly related to AZD7648 | 0 Participants |
| Cohort 1: AZD7648 Dose C1 + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE with outcome of death, possibly related to PLD | 0 Participants |
| Cohort 1: AZD7648 Dose C1 + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE leading to AZD7648 dose reduction | 1 Participants |
| Cohort 1: AZD7648 Dose C1 + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE with outcome of death, possibly related to PLD | 0 Participants |
| Cohort 1: AZD7648 Dose C1 + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE leading to PLD dose interruption | 2 Participants |
| Cohort 1: AZD7648 Dose C1 + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE possibly related to PLD | 2 Participants |
| Cohort 1: AZD7648 Dose C1 + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE | 1 Participants |
| Cohort 1: AZD7648 Dose C1 + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE leading to AZD7648 dose modification | 2 Participants |
| Cohort 1: AZD7648 Dose C1 + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE of CTCAE Grade 3 or higher, possibly related to PLD | 2 Participants |
| Cohort 1: AZD7648 Dose C1 + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE leading to AZD7648 dose interruption | 2 Participants |
| Cohort 1: AZD7648 Dose C1 + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE, possibly related to PLD | 1 Participants |
| Cohort 1: AZD7648 Dose C1 + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE | 2 Participants |
| Cohort 1: AZD7648 Dose C1 + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE causing discontinuation of AZD7648 | 0 Participants |
| Cohort 1: AZD7648 Dose C1 + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE, possibly related to AZD7648 | 1 Participants |
| Cohort 1: AZD7648 Dose C1 + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE causing discontinuation of AZD7648, possibly related to PLD | 0 Participants |
| Cohort 1: AZD7648 Dose C1 + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE with outcome of death | 0 Participants |
| Cohort 1: AZD7648 Dose C1 + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE leading to discontinuation of AZD7648 | 0 Participants |
| Cohort 1: AZD7648 Dose C1 + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE of CTCAE Grade 3 or higher, possibly related to AZD7648 | 2 Participants |
| Cohort 1: AZD7648 Dose C1 + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE possibly related to AZD7648 | 2 Participants |
| Cohort 1: AZD7648 Dose C1 + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE with outcome of death | 0 Participants |
| Cohort 1: AZD7648 Dose C1 + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE with outcome of death, possibly related to AZD7648 | 0 Participants |
| Cohort 1: AZD7648 Dose C1 + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE of CTCAE Grade 3 or higher | 2 Participants |
| Cohort 1: AZD7648 Dose C1 + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE leading to PLD dose modification | 2 Participants |
| Cohort 1: AZD7648 Dose C1 + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE causing discontinuation of AZD7648, possibly related to AZD7648 | 0 Participants |
| Cohort 1: AZD7648 Dose C1 + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE leading to discontinuation of PLD | 0 Participants |
| Cohort 1: AZD7648 Dose C1 + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE leading to PLD dose reduction | 0 Participants |
| Cohort 1: AZD7648 Dose C + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE with outcome of death | 0 Participants |
| Cohort 1: AZD7648 Dose C + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE causing discontinuation of AZD7648, possibly related to PLD | 0 Participants |
| Cohort 1: AZD7648 Dose C + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE, possibly related to AZD7648 | 0 Participants |
| Cohort 1: AZD7648 Dose C + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE leading to PLD dose reduction | 0 Participants |
| Cohort 1: AZD7648 Dose C + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE | 1 Participants |
| Cohort 1: AZD7648 Dose C + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE possibly related to PLD | 2 Participants |
| Cohort 1: AZD7648 Dose C + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE leading to PLD dose modification | 1 Participants |
| Cohort 1: AZD7648 Dose C + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE leading to discontinuation of AZD7648 | 1 Participants |
| Cohort 1: AZD7648 Dose C + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE with outcome of death, possibly related to AZD7648 | 0 Participants |
| Cohort 1: AZD7648 Dose C + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE leading to AZD7648 dose reduction | 0 Participants |
| Cohort 1: AZD7648 Dose C + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE leading to discontinuation of PLD | 1 Participants |
| Cohort 1: AZD7648 Dose C + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE with outcome of death | 0 Participants |
| Cohort 1: AZD7648 Dose C + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE, possibly related to PLD | 0 Participants |
| Cohort 1: AZD7648 Dose C + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE with outcome of death, possibly related to AZD7648 | 0 Participants |
| Cohort 1: AZD7648 Dose C + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE with outcome of death, possibly related to PLD | 0 Participants |
| Cohort 1: AZD7648 Dose C + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE leading to PLD dose interruption | 1 Participants |
| Cohort 1: AZD7648 Dose C + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE with outcome of death, possibly related to PLD | 0 Participants |
| Cohort 1: AZD7648 Dose C + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE leading to AZD7648 dose interruption | 2 Participants |
| Cohort 1: AZD7648 Dose C + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE of CTCAE Grade 3 or higher, possibly related to PLD | 2 Participants |
| Cohort 1: AZD7648 Dose C + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE causing discontinuation of AZD7648 | 0 Participants |
| Cohort 1: AZD7648 Dose C + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE leading to AZD7648 dose modification | 2 Participants |
| Cohort 1: AZD7648 Dose C + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE | 2 Participants |
| Cohort 1: AZD7648 Dose C + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE of CTCAE Grade 3 or higher, possibly related to AZD7648 | 2 Participants |
| Cohort 1: AZD7648 Dose C + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE of CTCAE Grade 3 or higher | 2 Participants |
| Cohort 1: AZD7648 Dose C + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE causing discontinuation of AZD7648, possibly related to AZD7648 | 0 Participants |
| Cohort 1: AZD7648 Dose C + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE possibly related to AZD7648 | 2 Participants |
| Cohort 2: AZD7648 Dose C2 + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE, possibly related to AZD7648 | 0 Participants |
| Cohort 2: AZD7648 Dose C2 + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE, possibly related to PLD | 0 Participants |
| Cohort 2: AZD7648 Dose C2 + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE with outcome of death, possibly related to PLD | 0 Participants |
| Cohort 2: AZD7648 Dose C2 + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE with outcome of death, possibly related to AZD7648 | 0 Participants |
| Cohort 2: AZD7648 Dose C2 + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE with outcome of death | 0 Participants |
| Cohort 2: AZD7648 Dose C2 + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE with outcome of death | 0 Participants |
| Cohort 2: AZD7648 Dose C2 + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE leading to AZD7648 dose modification | 1 Participants |
| Cohort 2: AZD7648 Dose C2 + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE with outcome of death, possibly related to AZD7648 | 0 Participants |
| Cohort 2: AZD7648 Dose C2 + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE with outcome of death, possibly related to PLD | 0 Participants |
| Cohort 2: AZD7648 Dose C2 + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE of CTCAE Grade 3 or higher, possibly related to PLD | 0 Participants |
| Cohort 2: AZD7648 Dose C2 + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE of CTCAE Grade 3 or higher, possibly related to AZD7648 | 0 Participants |
| Cohort 2: AZD7648 Dose C2 + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE causing discontinuation of AZD7648 | 0 Participants |
| Cohort 2: AZD7648 Dose C2 + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE of CTCAE Grade 3 or higher | 0 Participants |
| Cohort 2: AZD7648 Dose C2 + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE causing discontinuation of AZD7648, possibly related to AZD7648 | 0 Participants |
| Cohort 2: AZD7648 Dose C2 + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE causing discontinuation of AZD7648, possibly related to PLD | 0 Participants |
| Cohort 2: AZD7648 Dose C2 + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE possibly related to PLD | 4 Participants |
| Cohort 2: AZD7648 Dose C2 + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE leading to discontinuation of AZD7648 | 1 Participants |
| Cohort 2: AZD7648 Dose C2 + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE leading to discontinuation of PLD | 1 Participants |
| Cohort 2: AZD7648 Dose C2 + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE possibly related to AZD7648 | 4 Participants |
| Cohort 2: AZD7648 Dose C2 + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE leading to PLD dose modification | 1 Participants |
| Cohort 2: AZD7648 Dose C2 + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE leading to AZD7648 dose reduction | 0 Participants |
| Cohort 2: AZD7648 Dose C2 + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE leading to PLD dose reduction | 0 Participants |
| Cohort 2: AZD7648 Dose C2 + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE | 4 Participants |
| Cohort 2: AZD7648 Dose C2 + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE leading to AZD7648 dose interruption | 1 Participants |
| Cohort 2: AZD7648 Dose C2 + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE leading to PLD dose interruption | 1 Participants |
| Cohort 2: AZD7648 Dose C2 + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE | 0 Participants |
| Cohort 3: AZD7648 Dose X + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE causing discontinuation of AZD7648, possibly related to PLD | 0 Participants |
| Cohort 3: AZD7648 Dose X + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE with outcome of death | 1 Participants |
| Cohort 3: AZD7648 Dose X + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE leading to PLD dose reduction | 1 Participants |
| Cohort 3: AZD7648 Dose X + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE causing discontinuation of AZD7648, possibly related to AZD7648 | 0 Participants |
| Cohort 3: AZD7648 Dose X + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE of CTCAE Grade 3 or higher | 5 Participants |
| Cohort 3: AZD7648 Dose X + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE | 7 Participants |
| Cohort 3: AZD7648 Dose X + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE with outcome of death, possibly related to AZD7648 | 0 Participants |
| Cohort 3: AZD7648 Dose X + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE causing discontinuation of AZD7648 | 0 Participants |
| Cohort 3: AZD7648 Dose X + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE leading to AZD7648 dose modification | 5 Participants |
| Cohort 3: AZD7648 Dose X + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE leading to PLD dose modification | 5 Participants |
| Cohort 3: AZD7648 Dose X + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE of CTCAE Grade 3 or higher, possibly related to AZD7648 | 4 Participants |
| Cohort 3: AZD7648 Dose X + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE of CTCAE Grade 3 or higher, possibly related to PLD | 1 Participants |
| Cohort 3: AZD7648 Dose X + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE with outcome of death, possibly related to PLD | 0 Participants |
| Cohort 3: AZD7648 Dose X + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE leading to AZD7648 dose interruption | 4 Participants |
| Cohort 3: AZD7648 Dose X + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE with outcome of death, possibly related to PLD | 0 Participants |
| Cohort 3: AZD7648 Dose X + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE with outcome of death, possibly related to AZD7648 | 0 Participants |
| Cohort 3: AZD7648 Dose X + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE with outcome of death | 1 Participants |
| Cohort 3: AZD7648 Dose X + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE leading to PLD dose interruption | 4 Participants |
| Cohort 3: AZD7648 Dose X + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE possibly related to AZD7648 | 7 Participants |
| Cohort 3: AZD7648 Dose X + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE, possibly related to PLD | 0 Participants |
| Cohort 3: AZD7648 Dose X + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE | 4 Participants |
| Cohort 3: AZD7648 Dose X + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE leading to discontinuation of PLD | 1 Participants |
| Cohort 3: AZD7648 Dose X + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE leading to discontinuation of AZD7648 | 1 Participants |
| Cohort 3: AZD7648 Dose X + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any SAE, possibly related to AZD7648 | 2 Participants |
| Cohort 3: AZD7648 Dose X + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE leading to AZD7648 dose reduction | 1 Participants |
| Cohort 3: AZD7648 Dose X + PLD (Combination Therapy) | Number of Patients With Adverse Events or Serious Adverse Events | Any AE possibly related to PLD | 4 Participants |
Primary
Number of Patients With Dose Limiting Toxicities (DLTs)
A DLT is defined as an AE that occurs from the first dose of study treatment up to and including Cycle 1, Day 28 (the DLT assessment period) that is assessed as unrelated to the disease, intercurrent illness, or concomitant medications.
Time frame: From Screening (Day -28) till study drug discontinuation (3.2 years)
Population: All patients who received at least 1 dose of any study treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1: AZD7648 Dose A (Monotherapy) | Number of Patients With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Cohort 2: AZD7648 Dose A1 (Monotherapy) | Number of Patients With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Cohort 3: AZD7648 Dose B1 (Monotherapy) | Number of Patients With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Cohort 4: AZD7648 Dose C1 (Monotherapy) | Number of Patients With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Cohort 5: AZD7648 Dose D1 (Monotherapy) | Number of Patients With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Cohort 6: AZD7648 Dose E1 (Monotherapy) | Number of Patients With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Cohort 7: AZD7648 Dose F1 (Monotherapy) | Number of Patients With Dose Limiting Toxicities (DLTs) | 1 Participants |
| Cohort 1: AZD7648 Dose C1 + PLD (Combination Therapy) | Number of Patients With Dose Limiting Toxicities (DLTs) | 2 Participants |
| Cohort 1: AZD7648 Dose C + PLD (Combination Therapy) | Number of Patients With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Cohort 2: AZD7648 Dose C2 + PLD (Combination Therapy) | Number of Patients With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Cohort 3: AZD7648 Dose X + PLD (Combination Therapy) | Number of Patients With Dose Limiting Toxicities (DLTs) | 1 Participants |
Secondary
Accumulation Ratio for Area Under Curve (Rac AUC)
The Rac AUC of AZD7648, following a single dose and at steady state after multiple dosing, when given orally as monotherapy and in combination with anti-cancer agents. Accumulation ratio for AUC, calculated by multiple dose AUCτ/single dose AUC(0-12) or AUC(0-24).
Time frame: Monotherapy: Cycle 1 Day 8 Pre-dose to 12 hours post dose; Combination therapy: Cycle 1 Days 7 and 8 Pre-dose to 8 hours post dose (each cycle is 28 days)
Population: All patients who received at least 1 dose of any study treatment and had at least 1 reportable post first dose concentration without any protocol deviations that might have affected PK.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Cohort 1: AZD7648 Dose A (Monotherapy) | Accumulation Ratio for Area Under Curve (Rac AUC) | NA Ratio |
| Cohort 3: AZD7648 Dose B1 (Monotherapy) | Accumulation Ratio for Area Under Curve (Rac AUC) | NA Ratio |
| Cohort 4: AZD7648 Dose C1 (Monotherapy) | Accumulation Ratio for Area Under Curve (Rac AUC) | NA Ratio |
| Cohort 1: AZD7648 Dose C1 + PLD (Combination Therapy) | Accumulation Ratio for Area Under Curve (Rac AUC) | NA Ratio |
| Cohort 1: AZD7648 Dose C + PLD (Combination Therapy) | Accumulation Ratio for Area Under Curve (Rac AUC) | NA Ratio |
| Cohort 2: AZD7648 Dose C2 + PLD (Combination Therapy) | Accumulation Ratio for Area Under Curve (Rac AUC) | NA Ratio |
Secondary
Accumulation Ratio for Cmax (Rac Cmax)
The Rac Cmax of AZD7648, following a single dose and at steady state after multiple dosing, when given orally as monotherapy and in combination with anti-cancer agents. Accumulation ratio for Cmax, calculated by multiple dose Cmax/single dose Cmax.
Time frame: Monotherapy: Cycle 1 Day 8 Pre-dose to 12 hours post dose; Combination therapy: Cycle 1 Days 7 and 8 Pre-dose to 8 hours post dose (each cycle is 28 days)
Population: All patients who received at least 1 dose of any study treatment and had at least 1 reportable post first dose concentration without any protocol deviations that might have affected PK.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: AZD7648 Dose A (Monotherapy) | Accumulation Ratio for Cmax (Rac Cmax) | NA Ratio | — |
| Cohort 3: AZD7648 Dose B1 (Monotherapy) | Accumulation Ratio for Cmax (Rac Cmax) | NA Ratio | — |
| Cohort 4: AZD7648 Dose C1 (Monotherapy) | Accumulation Ratio for Cmax (Rac Cmax) | NA Ratio | — |
| Cohort 5: AZD7648 Dose D1 (Monotherapy) | Accumulation Ratio for Cmax (Rac Cmax) | NA Ratio | — |
| Cohort 6: AZD7648 Dose E1 (Monotherapy) | Accumulation Ratio for Cmax (Rac Cmax) | NA Ratio | — |
| Cohort 7: AZD7648 Dose F1 (Monotherapy) | Accumulation Ratio for Cmax (Rac Cmax) | 1.348 Ratio | Geometric Coefficient of Variation 1.272 |
| Cohort 1: AZD7648 Dose C1 + PLD (Combination Therapy) | Accumulation Ratio for Cmax (Rac Cmax) | NA Ratio | — |
| Cohort 1: AZD7648 Dose C + PLD (Combination Therapy) | Accumulation Ratio for Cmax (Rac Cmax) | NA Ratio | — |
| Cohort 2: AZD7648 Dose C2 + PLD (Combination Therapy) | Accumulation Ratio for Cmax (Rac Cmax) | 1.157 Ratio | Geometric Coefficient of Variation 23.99 |
Secondary
Area Under Plasma Concentration-time Curve From Zero to Infinity (AUCinf)
The AUCinf of AZD7648, following a single dose and at steady state after multiple dosing, when given orally as monotherapy and in combination with anti-cancer agents.
Time frame: Monotherapy and Combination therapy: Cycle 0 Day 1 Pre-dose to 72 hours post-dose [each cycle is 28 days]
Population: All patients who received at least 1 dose of any study treatment and had at least 1 reportable post first dose concentration without any protocol deviations that might have affected pharmacokinetic (PK).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: AZD7648 Dose A (Monotherapy) | Area Under Plasma Concentration-time Curve From Zero to Infinity (AUCinf) | NA h*nmol/L | — |
| Cohort 2: AZD7648 Dose A1 (Monotherapy) | Area Under Plasma Concentration-time Curve From Zero to Infinity (AUCinf) | NA h*nmol/L | — |
| Cohort 3: AZD7648 Dose B1 (Monotherapy) | Area Under Plasma Concentration-time Curve From Zero to Infinity (AUCinf) | NA h*nmol/L | — |
| Cohort 4: AZD7648 Dose C1 (Monotherapy) | Area Under Plasma Concentration-time Curve From Zero to Infinity (AUCinf) | NA h*nmol/L | — |
| Cohort 5: AZD7648 Dose D1 (Monotherapy) | Area Under Plasma Concentration-time Curve From Zero to Infinity (AUCinf) | NA h*nmol/L | — |
| Cohort 6: AZD7648 Dose E1 (Monotherapy) | Area Under Plasma Concentration-time Curve From Zero to Infinity (AUCinf) | 25180 h*nmol/L | Standard Deviation 48.76 |
| Cohort 7: AZD7648 Dose F1 (Monotherapy) | Area Under Plasma Concentration-time Curve From Zero to Infinity (AUCinf) | 29680 h*nmol/L | Standard Deviation 19.72 |
| Cohort 1: AZD7648 Dose C1 + PLD (Combination Therapy) | Area Under Plasma Concentration-time Curve From Zero to Infinity (AUCinf) | NA h*nmol/L | — |
| Cohort 1: AZD7648 Dose C + PLD (Combination Therapy) | Area Under Plasma Concentration-time Curve From Zero to Infinity (AUCinf) | NA h*nmol/L | — |
| Cohort 2: AZD7648 Dose C2 + PLD (Combination Therapy) | Area Under Plasma Concentration-time Curve From Zero to Infinity (AUCinf) | 3826 h*nmol/L | Standard Deviation 55.72 |
| Cohort 3: AZD7648 Dose X + PLD (Combination Therapy) | Area Under Plasma Concentration-time Curve From Zero to Infinity (AUCinf) | 5539 h*nmol/L | Standard Deviation 52.04 |
Secondary
Area Under Plasma Concentration-time Curve in the Dosing Interval τ (AUCτ)
The AUCτ of AZD7648, at steady state after multiple dosing, when given orally as monotherapy and in combination with anti-cancer agents.
Time frame: Monotherapy and Combination therapy: Cycle 0 Day 1 Pre-dose to 72 hours post-dose (each cycle is 28 days)
Population: All patients who received at least 1 dose of any study treatment and had at least 1 reportable post first dose concentration without any protocol deviations that might have affected PK.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Cohort 1: AZD7648 Dose A (Monotherapy) | Area Under Plasma Concentration-time Curve in the Dosing Interval τ (AUCτ) | NA h*nmol/L |
| Cohort 3: AZD7648 Dose B1 (Monotherapy) | Area Under Plasma Concentration-time Curve in the Dosing Interval τ (AUCτ) | NA h*nmol/L |
| Cohort 4: AZD7648 Dose C1 (Monotherapy) | Area Under Plasma Concentration-time Curve in the Dosing Interval τ (AUCτ) | NA h*nmol/L |
| Cohort 1: AZD7648 Dose C1 + PLD (Combination Therapy) | Area Under Plasma Concentration-time Curve in the Dosing Interval τ (AUCτ) | NA h*nmol/L |
| Cohort 1: AZD7648 Dose C + PLD (Combination Therapy) | Area Under Plasma Concentration-time Curve in the Dosing Interval τ (AUCτ) | NA h*nmol/L |
| Cohort 2: AZD7648 Dose C2 + PLD (Combination Therapy) | Area Under Plasma Concentration-time Curve in the Dosing Interval τ (AUCτ) | NA h*nmol/L |
Secondary
Area Under the Plasma Concentration-curve From Zero to the Last Quantifiable Concentration (AUClast)
The AUClast of AZD7648, following a single dose, when given orally as monotherapy and in combination with anti-cancer agents.
Time frame: Monotherapy and Combination therapy: Cycle 0 Day 1 Pre-dose to 72 hours post-dose (each cycle is 28 days)
Population: All patients who received at least 1 dose of any study treatment and had at least 1 reportable post first dose concentration without any protocol deviations that might have affected PK.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: AZD7648 Dose A (Monotherapy) | Area Under the Plasma Concentration-curve From Zero to the Last Quantifiable Concentration (AUClast) | NA h*nmol/L | — |
| Cohort 2: AZD7648 Dose A1 (Monotherapy) | Area Under the Plasma Concentration-curve From Zero to the Last Quantifiable Concentration (AUClast) | NA h*nmol/L | — |
| Cohort 3: AZD7648 Dose B1 (Monotherapy) | Area Under the Plasma Concentration-curve From Zero to the Last Quantifiable Concentration (AUClast) | NA h*nmol/L | — |
| Cohort 4: AZD7648 Dose C1 (Monotherapy) | Area Under the Plasma Concentration-curve From Zero to the Last Quantifiable Concentration (AUClast) | NA h*nmol/L | — |
| Cohort 5: AZD7648 Dose D1 (Monotherapy) | Area Under the Plasma Concentration-curve From Zero to the Last Quantifiable Concentration (AUClast) | NA h*nmol/L | — |
| Cohort 6: AZD7648 Dose E1 (Monotherapy) | Area Under the Plasma Concentration-curve From Zero to the Last Quantifiable Concentration (AUClast) | 24940 h*nmol/L | Geometric Coefficient of Variation 49.04 |
| Cohort 7: AZD7648 Dose F1 (Monotherapy) | Area Under the Plasma Concentration-curve From Zero to the Last Quantifiable Concentration (AUClast) | 29540 h*nmol/L | Geometric Coefficient of Variation 19.64 |
| Cohort 1: AZD7648 Dose C1 + PLD (Combination Therapy) | Area Under the Plasma Concentration-curve From Zero to the Last Quantifiable Concentration (AUClast) | NA h*nmol/L | — |
| Cohort 1: AZD7648 Dose C + PLD (Combination Therapy) | Area Under the Plasma Concentration-curve From Zero to the Last Quantifiable Concentration (AUClast) | NA h*nmol/L | — |
| Cohort 2: AZD7648 Dose C2 + PLD (Combination Therapy) | Area Under the Plasma Concentration-curve From Zero to the Last Quantifiable Concentration (AUClast) | 3798 h*nmol/L | Geometric Coefficient of Variation 55.78 |
| Cohort 3: AZD7648 Dose X + PLD (Combination Therapy) | Area Under the Plasma Concentration-curve From Zero to the Last Quantifiable Concentration (AUClast) | 5509 h*nmol/L | Geometric Coefficient of Variation 52.19 |
Secondary
Dose Proportionality (TCP)
The TCP of AZD7648, following a single dose and at steady state after multiple dosing, when given orally as monotherapy and in combination with anti-cancer agents. Temporal change parameter in systemic exposure, calculated as multiple dose AUCtau/single dose AUCinf.
Time frame: Monotherapy: Cycle 1 Day 8 Pre-dose to 12 hours post dose; Combination therapy: Cycle 1 Days 7 and 8 Pre-dose to 8 hours post dose (each cycle is 28 days)
Population: All patients who received at least 1 dose of any study treatment and had at least 1 reportable post first dose concentration without any protocol deviations that might have affected PK.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Cohort 1: AZD7648 Dose A (Monotherapy) | Dose Proportionality (TCP) | NA Ratio |
| Cohort 3: AZD7648 Dose B1 (Monotherapy) | Dose Proportionality (TCP) | NA Ratio |
| Cohort 4: AZD7648 Dose C1 (Monotherapy) | Dose Proportionality (TCP) | NA Ratio |
| Cohort 1: AZD7648 Dose C1 + PLD (Combination Therapy) | Dose Proportionality (TCP) | NA Ratio |
| Cohort 1: AZD7648 Dose C + PLD (Combination Therapy) | Dose Proportionality (TCP) | NA Ratio |
| Cohort 2: AZD7648 Dose C2 + PLD (Combination Therapy) | Dose Proportionality (TCP) | NA Ratio |
Secondary
Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t½λz)
The t½λ of AZD7648, following a single dose and at steady state after multiple dosing, when given orally as monotherapy and in combination with anti-cancer agents.
Time frame: Monotherapy and Combination therapy: Cycle 0 Day 1 Pre-dose to 72 hours post-dose (each cycle is 28 days)
Population: All patients who received at least 1 dose of any study treatment and had at least 1 reportable post first dose concentration without any protocol deviations that might have affected PK.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: AZD7648 Dose A (Monotherapy) | Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t½λz) | NA Hours | — |
| Cohort 2: AZD7648 Dose A1 (Monotherapy) | Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t½λz) | NA Hours | — |
| Cohort 3: AZD7648 Dose B1 (Monotherapy) | Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t½λz) | NA Hours | — |
| Cohort 4: AZD7648 Dose C1 (Monotherapy) | Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t½λz) | NA Hours | — |
| Cohort 5: AZD7648 Dose D1 (Monotherapy) | Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t½λz) | NA Hours | — |
| Cohort 6: AZD7648 Dose E1 (Monotherapy) | Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t½λz) | 10.32 Hours | Geometric Coefficient of Variation 39.41 |
| Cohort 7: AZD7648 Dose F1 (Monotherapy) | Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t½λz) | 10.64 Hours | Geometric Coefficient of Variation 27.39 |
| Cohort 1: AZD7648 Dose C1 + PLD (Combination Therapy) | Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t½λz) | NA Hours | — |
| Cohort 1: AZD7648 Dose C + PLD (Combination Therapy) | Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t½λz) | NA Hours | — |
| Cohort 2: AZD7648 Dose C2 + PLD (Combination Therapy) | Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t½λz) | 6.506 Hours | Geometric Coefficient of Variation 44.51 |
| Cohort 3: AZD7648 Dose X + PLD (Combination Therapy) | Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t½λz) | 7.562 Hours | Geometric Coefficient of Variation 51.64 |
Secondary
Maximum Observed Plasma (Peak) Drug Concentration After Single Dose and Multiple Doses (Cmax)
The Cmax of AZD7648, following a single dose and at steady state after multiple dosing, when given orally as monotherapy and in combination with anti-cancer agents.
Time frame: Monotherapy: Cycle 0 Day 1 Pre-dose to 72 hours post-dose, Cycle 1 Day 8 Pre-dose to 12 hours post dose; Combination therapy: Cycle 0 Day 1 Pre-dose to 12 hours post dose and Cycle 1 Days 7, 8 Pre-dose to 8 hours post dose (each cycle is 28 days)
Population: All patients who received at least 1 dose of any study treatment and had at least 1 reportable post first dose concentration without any protocol deviations that might have affected PK.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: AZD7648 Dose A (Monotherapy) | Maximum Observed Plasma (Peak) Drug Concentration After Single Dose and Multiple Doses (Cmax) | Cycle 0 Day 1 | NA nmol/L | — |
| Cohort 1: AZD7648 Dose A (Monotherapy) | Maximum Observed Plasma (Peak) Drug Concentration After Single Dose and Multiple Doses (Cmax) | Cycle 1 Day 7 Cycle 1 Day 8 | NA nmol/L | — |
| Cohort 2: AZD7648 Dose A1 (Monotherapy) | Maximum Observed Plasma (Peak) Drug Concentration After Single Dose and Multiple Doses (Cmax) | Cycle 0 Day 1 | NA nmol/L | — |
| Cohort 2: AZD7648 Dose A1 (Monotherapy) | Maximum Observed Plasma (Peak) Drug Concentration After Single Dose and Multiple Doses (Cmax) | Cycle 1 Day 7 Cycle 1 Day 8 | NA nmol/L | — |
| Cohort 3: AZD7648 Dose B1 (Monotherapy) | Maximum Observed Plasma (Peak) Drug Concentration After Single Dose and Multiple Doses (Cmax) | Cycle 0 Day 1 | NA nmol/L | — |
| Cohort 3: AZD7648 Dose B1 (Monotherapy) | Maximum Observed Plasma (Peak) Drug Concentration After Single Dose and Multiple Doses (Cmax) | Cycle 1 Day 7 Cycle 1 Day 8 | NA nmol/L | — |
| Cohort 4: AZD7648 Dose C1 (Monotherapy) | Maximum Observed Plasma (Peak) Drug Concentration After Single Dose and Multiple Doses (Cmax) | Cycle 0 Day 1 | NA nmol/L | — |
| Cohort 4: AZD7648 Dose C1 (Monotherapy) | Maximum Observed Plasma (Peak) Drug Concentration After Single Dose and Multiple Doses (Cmax) | Cycle 1 Day 7 Cycle 1 Day 8 | NA nmol/L | — |
| Cohort 5: AZD7648 Dose D1 (Monotherapy) | Maximum Observed Plasma (Peak) Drug Concentration After Single Dose and Multiple Doses (Cmax) | Cycle 1 Day 7 Cycle 1 Day 8 | NA nmol/L | — |
| Cohort 5: AZD7648 Dose D1 (Monotherapy) | Maximum Observed Plasma (Peak) Drug Concentration After Single Dose and Multiple Doses (Cmax) | Cycle 0 Day 1 | NA nmol/L | — |
| Cohort 6: AZD7648 Dose E1 (Monotherapy) | Maximum Observed Plasma (Peak) Drug Concentration After Single Dose and Multiple Doses (Cmax) | Cycle 1 Day 7 Cycle 1 Day 8 | NA nmol/L | — |
| Cohort 6: AZD7648 Dose E1 (Monotherapy) | Maximum Observed Plasma (Peak) Drug Concentration After Single Dose and Multiple Doses (Cmax) | Cycle 0 Day 1 | 2463 nmol/L | Geometric Coefficient of Variation 56.72 |
| Cohort 7: AZD7648 Dose F1 (Monotherapy) | Maximum Observed Plasma (Peak) Drug Concentration After Single Dose and Multiple Doses (Cmax) | Cycle 1 Day 7 Cycle 1 Day 8 | 5426 nmol/L | Geometric Coefficient of Variation 12.75 |
| Cohort 7: AZD7648 Dose F1 (Monotherapy) | Maximum Observed Plasma (Peak) Drug Concentration After Single Dose and Multiple Doses (Cmax) | Cycle 0 Day 1 | 4026 nmol/L | Geometric Coefficient of Variation 13.97 |
| Cohort 1: AZD7648 Dose C1 + PLD (Combination Therapy) | Maximum Observed Plasma (Peak) Drug Concentration After Single Dose and Multiple Doses (Cmax) | Cycle 0 Day 1 | NA nmol/L | — |
| Cohort 1: AZD7648 Dose C1 + PLD (Combination Therapy) | Maximum Observed Plasma (Peak) Drug Concentration After Single Dose and Multiple Doses (Cmax) | Cycle 1 Day 7 Cycle 1 Day 8 | NA nmol/L | — |
| Cohort 1: AZD7648 Dose C + PLD (Combination Therapy) | Maximum Observed Plasma (Peak) Drug Concentration After Single Dose and Multiple Doses (Cmax) | Cycle 0 Day 1 | NA nmol/L | — |
| Cohort 2: AZD7648 Dose C2 + PLD (Combination Therapy) | Maximum Observed Plasma (Peak) Drug Concentration After Single Dose and Multiple Doses (Cmax) | Cycle 0 Day 1 | 376.8 nmol/L | Geometric Coefficient of Variation 27.66 |
| Cohort 2: AZD7648 Dose C2 + PLD (Combination Therapy) | Maximum Observed Plasma (Peak) Drug Concentration After Single Dose and Multiple Doses (Cmax) | Cycle 1 Day 7 Cycle 1 Day 8 | NA nmol/L | — |
| Cohort 3: AZD7648 Dose X + PLD (Combination Therapy) | Maximum Observed Plasma (Peak) Drug Concentration After Single Dose and Multiple Doses (Cmax) | Cycle 0 Day 1 | 754.2 nmol/L | Geometric Coefficient of Variation 34.29 |
| Cohort 3: AZD7648 Dose X + PLD (Combination Therapy) | Maximum Observed Plasma (Peak) Drug Concentration After Single Dose and Multiple Doses (Cmax) | Cycle 1 Day 7 Cycle 1 Day 8 | 944.9 nmol/L | Geometric Coefficient of Variation 62.85 |
Secondary
Objective Response Rate (ORR)
ORR is defined as the percentage of patients who have a confirmed visit response of complete response (CR) or partial response (PR) prior to any evidence of progression (as defined by Response Evaluation Criteria in Solid Tumours 1.1). CR is defined when all target lesions (TLs) and non-target lesions (NTLs) present at baseline have disappeared (with the exception of lymph nodes which must be \<10mm to be considered non pathological) and no new lesions have developed since baseline. PR is defined when the sum of diameters of the TLs has decreased by 30% or more compared to baseline (with no evidence of progression) and the NTLs are at least stable with no evidence of new lesions.
Time frame: First dose of study treatment on Cycle 1 Day 1 (each cycle is 28 days) until progression or the last evaluable assessment in the absence of progression (3.2 years)
Population: Evaluable for objective response set included all patients who had a measurable baseline disease (having at least one measurable target lesion, not previously irradiated, which is ≥ 10 mm in the longest diameter (LD) (except lymph nodes which must have short axis ≥ 15 mm) by RECIST 1.1 assessment and received at least one dose of any study treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: AZD7648 Dose A (Monotherapy) | Objective Response Rate (ORR) | 0 Percentage of participants |
| Cohort 2: AZD7648 Dose A1 (Monotherapy) | Objective Response Rate (ORR) | 0 Percentage of participants |
| Cohort 3: AZD7648 Dose B1 (Monotherapy) | Objective Response Rate (ORR) | 0 Percentage of participants |
| Cohort 4: AZD7648 Dose C1 (Monotherapy) | Objective Response Rate (ORR) | 0 Percentage of participants |
| Cohort 5: AZD7648 Dose D1 (Monotherapy) | Objective Response Rate (ORR) | 0 Percentage of participants |
| Cohort 6: AZD7648 Dose E1 (Monotherapy) | Objective Response Rate (ORR) | 0 Percentage of participants |
| Cohort 7: AZD7648 Dose F1 (Monotherapy) | Objective Response Rate (ORR) | 0 Percentage of participants |
| Cohort 1: AZD7648 Dose C1 + PLD (Combination Therapy) | Objective Response Rate (ORR) | 0 Percentage of participants |
| Cohort 1: AZD7648 Dose C + PLD (Combination Therapy) | Objective Response Rate (ORR) | 50 Percentage of participants |
| Cohort 2: AZD7648 Dose C2 + PLD (Combination Therapy) | Objective Response Rate (ORR) | 0 Percentage of participants |
| Cohort 3: AZD7648 Dose X + PLD (Combination Therapy) | Objective Response Rate (ORR) | 0 Percentage of participants |
Secondary
Progression Free Survival (PFS) for Combination Therapy
PFS is defined as the time from first dose of Cycle 1 until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from study therapy or receives another anti-cancer therapy prior to progression. Disease progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as increased by \> 20% or more compared to the smallest sum of diameters on study.
Time frame: At 18 months
Population: Evaluable for efficacy set included all patients who received at least 1 dose of any study treatment and have a baseline tumour assessment according to RECIST 1.1.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1: AZD7648 Dose A (Monotherapy) | Progression Free Survival (PFS) for Combination Therapy | NA Months |
| Cohort 2: AZD7648 Dose A1 (Monotherapy) | Progression Free Survival (PFS) for Combination Therapy | NA Months |
| Cohort 3: AZD7648 Dose B1 (Monotherapy) | Progression Free Survival (PFS) for Combination Therapy | 1.74 Months |
| Cohort 4: AZD7648 Dose C1 (Monotherapy) | Progression Free Survival (PFS) for Combination Therapy | 2.07 Months |
Secondary
Progression Free Survival (PFS) for Monotherapy
PFS is defined as the time from first dose of Cycle 1 until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from study therapy or receives another anti-cancer therapy prior to progression. Disease progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as increased by \> 20% or more compared to the smallest sum of diameters on study.
Time frame: At 12 months
Population: Evaluable for efficacy set included all patients who received at least 1 dose of any study treatment and have a baseline tumour assessment according to RECIST 1.1.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1: AZD7648 Dose A (Monotherapy) | Progression Free Survival (PFS) for Monotherapy | NA Months |
| Cohort 2: AZD7648 Dose A1 (Monotherapy) | Progression Free Survival (PFS) for Monotherapy | NA Months |
| Cohort 3: AZD7648 Dose B1 (Monotherapy) | Progression Free Survival (PFS) for Monotherapy | NA Months |
| Cohort 4: AZD7648 Dose C1 (Monotherapy) | Progression Free Survival (PFS) for Monotherapy | NA Months |
| Cohort 5: AZD7648 Dose D1 (Monotherapy) | Progression Free Survival (PFS) for Monotherapy | 1.91 Months |
| Cohort 6: AZD7648 Dose E1 (Monotherapy) | Progression Free Survival (PFS) for Monotherapy | 2.50 Months |
| Cohort 7: AZD7648 Dose F1 (Monotherapy) | Progression Free Survival (PFS) for Monotherapy | 1.51 Months |
Secondary
Time to Reach Maximum Plasma Concentration (Tmax)
The tmax of AZD7648, following a single dose and at steady state after multiple dosing, when given orally as monotherapy and in combination with anti-cancer agents.
Time frame: Monotherapy: Cycle 0 Day 1 Pre-dose to 72 hours post-dose, Cycle 1 Day 8 Pre-dose to 12 hours post dose; Combination therapy: Cycle 0 Day 1 Pre-dose to 12 hours post dose and Cycle 1 Days 7, 8 Pre-dose to 8 hours post dose (each cycle is 28 days)
Population: All patients who received at least 1 dose of any study treatment and had at least 1 reportable post first dose concentration without any protocol deviations that might have affected PK.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1: AZD7648 Dose A (Monotherapy) | Time to Reach Maximum Plasma Concentration (Tmax) | Cycle 0 Day 1 | NA Hours |
| Cohort 1: AZD7648 Dose A (Monotherapy) | Time to Reach Maximum Plasma Concentration (Tmax) | Cycle 1 Day 7 Cycle 1 Day 8 | NA Hours |
| Cohort 2: AZD7648 Dose A1 (Monotherapy) | Time to Reach Maximum Plasma Concentration (Tmax) | Cycle 0 Day 1 | NA Hours |
| Cohort 2: AZD7648 Dose A1 (Monotherapy) | Time to Reach Maximum Plasma Concentration (Tmax) | Cycle 1 Day 7 Cycle 1 Day 8 | NA Hours |
| Cohort 3: AZD7648 Dose B1 (Monotherapy) | Time to Reach Maximum Plasma Concentration (Tmax) | Cycle 0 Day 1 | NA Hours |
| Cohort 3: AZD7648 Dose B1 (Monotherapy) | Time to Reach Maximum Plasma Concentration (Tmax) | Cycle 1 Day 7 Cycle 1 Day 8 | NA Hours |
| Cohort 4: AZD7648 Dose C1 (Monotherapy) | Time to Reach Maximum Plasma Concentration (Tmax) | Cycle 0 Day 1 | NA Hours |
| Cohort 4: AZD7648 Dose C1 (Monotherapy) | Time to Reach Maximum Plasma Concentration (Tmax) | Cycle 1 Day 7 Cycle 1 Day 8 | NA Hours |
| Cohort 5: AZD7648 Dose D1 (Monotherapy) | Time to Reach Maximum Plasma Concentration (Tmax) | Cycle 0 Day 1 | NA Hours |
| Cohort 5: AZD7648 Dose D1 (Monotherapy) | Time to Reach Maximum Plasma Concentration (Tmax) | Cycle 1 Day 7 Cycle 1 Day 8 | NA Hours |
| Cohort 6: AZD7648 Dose E1 (Monotherapy) | Time to Reach Maximum Plasma Concentration (Tmax) | Cycle 1 Day 7 Cycle 1 Day 8 | NA Hours |
| Cohort 6: AZD7648 Dose E1 (Monotherapy) | Time to Reach Maximum Plasma Concentration (Tmax) | Cycle 0 Day 1 | 2.050 Hours |
| Cohort 7: AZD7648 Dose F1 (Monotherapy) | Time to Reach Maximum Plasma Concentration (Tmax) | Cycle 0 Day 1 | 2.033 Hours |
| Cohort 7: AZD7648 Dose F1 (Monotherapy) | Time to Reach Maximum Plasma Concentration (Tmax) | Cycle 1 Day 7 Cycle 1 Day 8 | 2.167 Hours |
| Cohort 1: AZD7648 Dose C1 + PLD (Combination Therapy) | Time to Reach Maximum Plasma Concentration (Tmax) | Cycle 1 Day 7 Cycle 1 Day 8 | NA Hours |
| Cohort 1: AZD7648 Dose C1 + PLD (Combination Therapy) | Time to Reach Maximum Plasma Concentration (Tmax) | Cycle 0 Day 1 | NA Hours |
| Cohort 1: AZD7648 Dose C + PLD (Combination Therapy) | Time to Reach Maximum Plasma Concentration (Tmax) | Cycle 0 Day 1 | NA Hours |
| Cohort 2: AZD7648 Dose C2 + PLD (Combination Therapy) | Time to Reach Maximum Plasma Concentration (Tmax) | Cycle 1 Day 7 Cycle 1 Day 8 | NA Hours |
| Cohort 2: AZD7648 Dose C2 + PLD (Combination Therapy) | Time to Reach Maximum Plasma Concentration (Tmax) | Cycle 0 Day 1 | 3.058 Hours |
| Cohort 3: AZD7648 Dose X + PLD (Combination Therapy) | Time to Reach Maximum Plasma Concentration (Tmax) | Cycle 0 Day 1 | 1.150 Hours |
| Cohort 3: AZD7648 Dose X + PLD (Combination Therapy) | Time to Reach Maximum Plasma Concentration (Tmax) | Cycle 1 Day 7 Cycle 1 Day 8 | 1.100 Hours |