Progressive Metastatic Castrate-Resistant Prostate Cancer
Conditions
Keywords
Prostate Cancer
Brief summary
This is a Phase II, international, open-label, two-arm, non-randomised study of AZD4635 in participants with metastatic castration-resistant prostate cancer (mCRPC).
Detailed description
This is a Phase II, international, open-label, two-arm, non-randomised study of AZD4635 in participants with mCRPC. Participants in each arm will be stratified by the presence of measurable soft tissue metastasis (per Response Evaluation Criteria in Solid Tumours \[RECIST v1.1\]) or bone-only metastasis (per Prostate Cancer Working Group 3 \[PCWG3 criteria\]). There will be no formal comparisons between treatment arms. AZD4635 plus durvalumab (Arm A) will consist of 80 participants with mCRPC previously treated with one or more approved new hormonal agent(s) (NHAs) and one or more taxanes or participants who are taxane ineligible. AZD4635 plus durvalumab plus cabazitaxel (Arm B) will consist of 80 participants mCRPC previously treated with docetaxel and one prior NHA. As of November 2020, the Sponsor stopped enrolment in Arm A following decisions at the program level, not related to any safety issues. Ongoing participants in Arm A may continue treatment as planned.
Interventions
DRUGAZD4635
Subjects will receive AZD4635 orally daily
DRUGDurvalumab
Subjects will receive intravenous durvalumab every 4 weeks for Arm A and every 3 weeks for Arm B.
DRUGCabazitaxel
Subjects will receive intravenous cabazitaxel every 3 weeks
Sponsors
Parexel
AstraZeneca
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 150 Years
Healthy volunteers
No
Inclusion criteria
1. Histologically confirmed adenocarcinoma of the prostate. 2. Known castrate-resistant disease. 3. Evidence of disease progression ≤6 months. 4. Body weight \>30 kg at screening. 5. Willingness to adhere to the study treatment-specific contraception requirements. 6. Adequate bone marrow reserve and organ function. 7. Adequate organ function for Arm A as demonstrated by all of the following laboratory values: * Alanine aminotransferase (ALT) ≤2.5 × upper limit of normal (ULN) if no demonstrable liver metastases or ≤5 × ULN in the presence of liver metastases. * Aspartate aminotransferase (AST) ≤2.5 × ULN if no demonstrable liver metastases or ≤5 × ULN in the presence of liver metastases * Total bilirubin (TBL) ≤1.5 × ULN * TBL ≤2.0 × ULN in the case of known Gilbert syndrome with normal direct bilirubin 8. Participants in Arm A must have received the following prior therapy: * Maximum of 3 lines of therapy in the mCRPC setting * Prior therapy with one or more NHAs (eg, abiraterone acetate, enzalutamide, apalutamide, darolutamide) in either hormone-sensitive or hormone-refractory settings * Prior therapy with one or more lines of taxanes (eg, docetaxel and/or cabazitaxel) * Alternatively, must be taxane-ineligible * Prior therapy can be in either the hormone-sensitive or the hormone-refractory setting 9. Adequate organ function for Arm B as demonstrated by all of the following laboratory values: * AST and/or ALT ≤1.5 × ULN * TBL ≤ ULN * TBL ≤2.0 × ULN in the case of known Gilbert syndrome with normal direct bilirubin 10. Participants in Arm B must have received the following prior therapy: * Prior docetaxel (taxane) in either hormone-sensitive or hormone-refractory settings * Received no prior cytotoxic chemotherapy other than docetaxel for prostate cancer except for estramustine and except adjuvant/neo-adjuvant treatment completed \>3 years ago. * Prior therapy with only one NHAs (eg, abiraterone acetate or enzalutamide; prior apalutamide is not permitted) for treatment of mCRPC in either hormone-sensitive or hormone-refractory settings. * Be suitable to receive concomitant Granulocyte-colony stimulating factor during all cycles of cabazitaxel. * Participants who meet inclusion criteria for Arm B will be allocated preferentially to that arm until recruitment to that arm is completed.
Exclusion criteria
1. Active brain metastases or leptomeningeal metastases. 2. There must be no requirement for immunosuppressive doses of systemic corticosteroids for at least 2 weeks prior to study enrollment. 3. History of pneumonitis requiring corticosteroids, second malignancy that is progressing and/or received active treatment ≤3 years before the first dose of study intervention, and hypersensitivity to polysorbate-80 if allocated to cabazitaxel. 4. As judged by the Investigator, any evidence of severe or uncontrolled systemic diseases. 5. Creatinine clearance \<40 mL/min (calculated by Cockcroft-Gault equation). 6. Prior exposure to immune-mediated therapy including. 7. Ongoing treatment with warfarin (Coumadin). 8. Major surgery (excluding placement of vascular access) within 4 weeks of the first dose of study intervention.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Radiographic Progression Free Survival (rPFS) in Each Arm Separately to Determine the Efficacy of AZD4635 Plus Durvalumab and of AZD4635 Plus Durvalumab Plus Cabazitaxel in Patients With Metastatic Castrate-resistant Prostate Cancer (mCRPC) | From first dose to first documented progression or death from any cause (whichever comes first) (approximately 1 year) | rPFS was defined as the time from first dose to radiographic progression, assessed by the Investigator per RECIST 1.1 (soft tissue) and PCWG3 (Prostate Cancer Working Group 3) criteria \[bone\] or death from any cause, whichever occurred first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) in Each Arm Separately to Determine the Efficacy of AZD4635 Plus Durvalumab and of AZD4635 Plus Durvalumab Plus Cabazitaxel in Participants With mCRPC | Arm A and B: Every 90 days from the last dose of study drug up to 2 years | OS was defined as the time from first dose until death due to any cause regardless of whether the participant withdrew from study treatment or received another anti-cancer therapy. |
| Number of Participants With Objective Response in Subjects With MCRPC Who Received AZD4635 Plus Durvalumab Plus Cabazitaxel | From first dose to first documented progression or death from any cause (whichever comes first), up to two years | Confirmed ORR was defined as the proportion of participants with a confirmed complete response (CR) or partial response (PR) using overall radiographic response assessed by RECIST v1.1 and PCWG-3 criteria (bone), and was based on a subset of all treated participants with measurable disease at baseline per the site Investigator. |
| Number of Participants With Prostate-specifin Antigen (PSA50) Response in Subjects With MCRPC Who Received AZD4635 Plus Durvalumab Plus Cabazitaxel | Arm A: Screening, Day 1 of each cycle up to 11 months (Each cycle was 28 days in length); Arm B: Screening, Day 1 of each cycle up to 11 months (Cycle 1 to Cycle 10 = 21 days, Cycle 11 onwards = 28 days) | Confirmed PSA50 response is defined as the proportion of participants who achieved a ≥50% decrease in PSA from baseline to the lowest post-baseline PSA, confirmed by a consecutive PSA at least 3 weeks later and was based on PSA evaluable participants (dosed participants with an abnormal baseline PSA \[≥1 ng/mL\]). |
| Change From Baseline in Worst Pain in the Daily Activities Scales of the Brief Pain Inventory - Short Form (BPI-SF) | Arm A: Screening, Day 1 of each cycle up to 9 months (Each cycle was 28 days in length); Arm B: Screening, Day 1 of each cycle up to 9 months (Each cycle was 21 days in length) | Worst pain and Average pain are 'single question' scores from the BPI short form and may take any value from 0 to 10 (worst outcome). Interference Pain is the total score of 7 sub-scores, where each value may take any value from 0 to 10 (worst outcome). The range of the Interference Score can be from 0 to 70. |
| Change From Baseline in Average Pain in the Daily Activities Scales of the Brief Pain Inventory - Short Form (BPI-SF) | Arm A: Screening, Day 1 of each cycle up to 9 months (Each cycle was 28 days in length); Arm B: Screening, Day 1 of each cycle up to 9 months (Each cycle was 21 days in length) | Worst pain and Average pain are 'single question' scores from the BPI short form and may take any value from 0 to 10 (worst outcome). Interference Pain is the total score of 7 sub-scores, where each value may take any value from 0 to 10 (worst outcome). The range of the Interference Score can be from 0 to 70. |
| Change From Baseline in Pain Interference in the Daily Activities Scales of the Brief Pain Inventory - Short Form (BPI-SF) | Arm A: Screening, Day 1 of each cycle up to 9 months (Each cycle was 28 days in length); Arm B: Screening, Day 1 of each cycle up to 9 months (Each cycle was 21 days in length) | Worst pain and Average pain are 'single question' scores from the BPI short form and may take any value from 0 to 10 (worst outcome). Interference Pain is the total score of 7 sub-scores, where each value may take any value from 0 to 10 (worst outcome). The range of the Interference Score can be from 0 to 70. |
| Number of Participants Who Progressed Based on BPI-SF Item 3 | Arm A: Screening, Day 1 of each cycle up to 12 months (Each cycle was 28 days in length); Arm B: Screening, Day 1 of each cycle up to 12 months (Cycle 1 to Cycle 10 = 21 days, Cycle 11 onwards = 28 days) | Pain progression was assessed using BPI-SF. |
| rPFS by Adenosine (ADO) Signalling Gene Expression in High and Low Subgroups to Determine the Efficacy of AZD4635 Plus Durvalumab Plus Cabazitaxel in Participants With mCRPC | From first dose to first documented progression or death from any cause (whichever comes first), up to two years | rPFS was defined as the time from first dose to radiographic progression, assessed by the Investigator per RECIST 1.1 (soft tissue) and PCWG3 criteria (bone) or death from any cause, whichever occurred first. |
| Maximum Observed Plasma Concentration (Cmax) | Arm A:Cycle 1 to 3, and Cycle 4 onwards, and 90-day follow-up (FU) visit up to 14 months [Each cycle was 28 days in length];Arm B: Cycle 1 to 7 and Cycle 11 onwards, and 90-day FU up to 14 months (Cycle 1 to Cycle 10 = 21 days, Cycle 11 onwards = 28 days) | Investigate the PK of AZD4635 when given in combination with durvalumab, and when given in combination with durvalumab plus cabazitaxel. |
| Terminal Half-life (t1/2λz) | Arm A:Cycle 1 to 3, and Cycle 4 onwards, and 90-day follow-up (FU) visit up to 14 months [Each cycle was 28 days in length];Arm B: Cycle 1 to 7 and Cycle 11 onwards, and 90-day FU up to 14 months (Cycle 1 to Cycle 10 = 21 days, Cycle 11 onwards = 28 days) | Investigated the PK of AZD4635 when given in combination with durvalumab, and when given in combination with durvalumab plus cabazitaxel. |
| Area Under the Plasma Concentration Time Curve From Zero to the Time of the Last Measurable Concentration (AUClast) | Arm A:Cycle 1 to 3, and Cycle 4 onwards, and 90-day follow-up (FU) visit up to 14 months [Each cycle was 28 days in length];Arm B: Cycle 1 to 7 and Cycle 11 onwards, and 90-day FU up to 14 months (Cycle 1 to Cycle 10 = 21 days, Cycle 11 onwards = 28 days) | Investigated the PK of AZD4635 when given in combination with durvalumab, and when given in combination with durvalumab plus cabazitaxel. |
| Area Under the Plasma Concentration Time Curve From Zero to 24 Hours [AUC(0-24)] | Arm A:Cycle 1 to 3, and Cycle 4 onwards, and 90-day follow-up (FU) visit up to 14 months [Each cycle was 28 days in length];Arm B: Cycle 1 to 7 and Cycle 11 onwards, and 90-day FU up to 14 months (Cycle 1 to Cycle 10 = 21 days, Cycle 11 onwards = 28 days) | Investigated the PK of AZD4635 when given in combination with durvalumab, and when given in combination with durvalumab plus cabazitaxel. |
| Area Under the Plasma Concentration Time Curve From Zero Extrapolated to Infinity (AUCinf) | Arm A:Cycle 1 to 3, and Cycle 4 onwards, and 90-day follow-up (FU) visit up to 14 months [Each cycle was 28 days in length];Arm B: Cycle 1 to 7 and Cycle 11 onwards, and 90-day FU up to 14 months (Cycle 1 to Cycle 10 = 21 days, Cycle 11 onwards = 28 days) | Investigated the PK of AZD4635 when given in combination with durvalumab, and when given in combination with durvalumab plus cabazitaxel. |
| Apparent Volume of Distribution During the Terminal Phase (Vz/F) | Arm A:Cycle 1 to 3, and Cycle 4 onwards, and 90-day follow-up (FU) visit up to 14 months [Each cycle was 28 days in length];Arm B: Cycle 1 to 7 and Cycle 11 onwards, and 90-day FU up to 14 months (Cycle 1 to Cycle 10 = 21 days, Cycle 11 onwards = 28 days) | Investigated the PK of AZD4635 when given in combination with durvalumab, and when given in combination with durvalumab plus cabazitaxel. |
| Number of Subjects With Serious and Non-serious Adverse Events | Arm A: From Screening up to 14 months (Each cycle was 28 days in length); Arm B: From Screening up to 14 months (Cycle 1 to Cycle 10 was 21 days in length, and Cycle 11 onwards was 28 days in length) | Safety and tolerability of each treatment regimen were assessed in participants with mCRPC. |
| Change From Baseline in the FACT Advanced Prostate Symptom Indext-6 (FAPSI-6), as Derived From 6 Items, the FAPSI-8 From 8 Items Within the FACT-P and the Prostate Cancer Symptoms (PCS), From the 12 Items in the Prostrate-specific Module of the FACT-P | Arm A: Screening, Day 1 of each cycle up to 9 months (Each cycle was 28 days in length); Arm B: Screening, Day 1 of each cycle up to 9 months (Each cycle was 21 days in length) | The Functional Assessment of Cancer Therapy-Prostate (FACT-P) will be used to measure health related quality of life (HRQL) in men with prostate cancer. It consists of 4 subscales (physical, emotional, functional and social/family well-being) plus a 12-item prostate-specific module, the PCS subscale, which highlights concerns specific to participants with prostate cancer. FAPSI-6 is defined as a symptom score made up of 6 items from within the FACT-P (pain \[n = 3\], fatigue \[n = 1\], weight loss \[n = 1\], and concerns about the condition getting worse \[n = 1\]). Each question in the FACT-P questionnaires has a choice of 5 responses, Not at all, A little bit, Somewhat, Quite a bit and Very much. The scores range from 0 (Not at all) to 4 (Very much) for positively phrased questions. Negatively phrased questions have a reverse scoring, from 0 (Very much) to 4 (Not at all). This results in a consistent approach, where higher scores indicate a better quality of life. |
Countries
Belgium, France, South Korea, Spain, United States
Participant flow
Recruitment details
Participants were enrolled in this study from 04-August-2020 to 08-August-2022.
Pre-assignment details
Participants who met the inclusion and none of the exclusion criteria were enrolled to the study. All study assessments were performed as per the schedule of assessment.
Participants by arm
| Arm | Count |
|---|---|
| Arm A: AZD4635 + Durvalumab Participants received AZD4635 Dose A orally daily, and durvalumab Dose B intravenously every 4 weeks. | 2 |
| Arm B: AZD4635 + Durvalumab + Cabazitaxel Participants received AZD4635 Dose A orally daily, durvalumab Dose B intravenously (IV) every 3 weeks (Q3W), and cabazitaxel Dose C IV Q3W | 28 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Death | 0 | 4 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Study terminated by sponsor | 0 | 18 |
| Overall Study | Withdrawal by Subject | 2 | 4 |
Baseline characteristics
| Characteristic | Total | Arm B: AZD4635 + Durvalumab + Cabazitaxel | Arm A: AZD4635 + Durvalumab |
|---|---|---|---|
| Age, Continuous | 68.0 years STANDARD_DEVIATION 8.18 | 68.0 years STANDARD_DEVIATION 8.18 | — |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 4 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 21 Participants | 21 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | 3 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 5 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 19 Participants | 19 Participants | 0 Participants |
| Sex/Gender, Customized Male | 28 Participants | 28 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 2 | 7 / 28 |
| other Total, other adverse events | 2 / 2 | 28 / 28 |
| serious Total, serious adverse events | 2 / 2 | 19 / 28 |
Outcome results
Primary
Radiographic Progression Free Survival (rPFS) in Each Arm Separately to Determine the Efficacy of AZD4635 Plus Durvalumab and of AZD4635 Plus Durvalumab Plus Cabazitaxel in Patients With Metastatic Castrate-resistant Prostate Cancer (mCRPC)
rPFS was defined as the time from first dose to radiographic progression, assessed by the Investigator per RECIST 1.1 (soft tissue) and PCWG3 (Prostate Cancer Working Group 3) criteria \[bone\] or death from any cause, whichever occurred first.
Time frame: From first dose to first documented progression or death from any cause (whichever comes first) (approximately 1 year)
Population: Evaluable for efficacy set consisted of dosed patients with a baseline tumour assessment. The data for Arm A was not calculated because of only two participants in this arm due to which there will be a patient identification risk.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm B: AZD4635 + Durvalumab + Cabazitaxel | Radiographic Progression Free Survival (rPFS) in Each Arm Separately to Determine the Efficacy of AZD4635 Plus Durvalumab and of AZD4635 Plus Durvalumab Plus Cabazitaxel in Patients With Metastatic Castrate-resistant Prostate Cancer (mCRPC) | 5.8 months |
Secondary
Apparent Volume of Distribution During the Terminal Phase (Vz/F)
Investigated the PK of AZD4635 when given in combination with durvalumab, and when given in combination with durvalumab plus cabazitaxel.
Time frame: Arm A:Cycle 1 to 3, and Cycle 4 onwards, and 90-day follow-up (FU) visit up to 14 months [Each cycle was 28 days in length];Arm B: Cycle 1 to 7 and Cycle 11 onwards, and 90-day FU up to 14 months (Cycle 1 to Cycle 10 = 21 days, Cycle 11 onwards = 28 days)
Population: The PK analysis set consisted of dosed participants for whom an adequate PK profile was obtained. The data for Arm A was not calculated because of only two participants in this arm due to which there will be a patient identification risk.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm B: AZD4635 + Durvalumab + Cabazitaxel | Apparent Volume of Distribution During the Terminal Phase (Vz/F) | 334.6 Litre | Standard Deviation 254.4 |
Secondary
Area Under the Plasma Concentration Time Curve From Zero Extrapolated to Infinity (AUCinf)
Investigated the PK of AZD4635 when given in combination with durvalumab, and when given in combination with durvalumab plus cabazitaxel.
Time frame: Arm A:Cycle 1 to 3, and Cycle 4 onwards, and 90-day follow-up (FU) visit up to 14 months [Each cycle was 28 days in length];Arm B: Cycle 1 to 7 and Cycle 11 onwards, and 90-day FU up to 14 months (Cycle 1 to Cycle 10 = 21 days, Cycle 11 onwards = 28 days)
Population: The PK analysis set consisted of dosed participants for whom an adequate PK profile was obtained. The data for Arm A was not calculated because of only two participants in this arm due to which there will be a patient identification risk.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm B: AZD4635 + Durvalumab + Cabazitaxel | Area Under the Plasma Concentration Time Curve From Zero Extrapolated to Infinity (AUCinf) | 3311 hour (h)*nanogram/millilitre (ng/mL) | Standard Deviation 1272 |
Secondary
Area Under the Plasma Concentration Time Curve From Zero to 24 Hours [AUC(0-24)]
Investigated the PK of AZD4635 when given in combination with durvalumab, and when given in combination with durvalumab plus cabazitaxel.
Time frame: Arm A:Cycle 1 to 3, and Cycle 4 onwards, and 90-day follow-up (FU) visit up to 14 months [Each cycle was 28 days in length];Arm B: Cycle 1 to 7 and Cycle 11 onwards, and 90-day FU up to 14 months (Cycle 1 to Cycle 10 = 21 days, Cycle 11 onwards = 28 days)
Population: The PK analysis set consisted of dosed participants for whom an adequate PK profile was obtained. The data for Arm A was not calculated because of only two participants in this arm due to which there will be a patient identification risk.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm B: AZD4635 + Durvalumab + Cabazitaxel | Area Under the Plasma Concentration Time Curve From Zero to 24 Hours [AUC(0-24)] | 2874 hour (h)*nanogram/millilitre (ng/mL) | Standard Deviation 1084 |
Secondary
Area Under the Plasma Concentration Time Curve From Zero to the Time of the Last Measurable Concentration (AUClast)
Investigated the PK of AZD4635 when given in combination with durvalumab, and when given in combination with durvalumab plus cabazitaxel.
Time frame: Arm A:Cycle 1 to 3, and Cycle 4 onwards, and 90-day follow-up (FU) visit up to 14 months [Each cycle was 28 days in length];Arm B: Cycle 1 to 7 and Cycle 11 onwards, and 90-day FU up to 14 months (Cycle 1 to Cycle 10 = 21 days, Cycle 11 onwards = 28 days)
Population: The PK analysis set consisted of dosed participants for whom an adequate PK profile was obtained. The data for Arm A was not calculated because of only two participants in this arm due to which there will be a patient identification risk.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm B: AZD4635 + Durvalumab + Cabazitaxel | Area Under the Plasma Concentration Time Curve From Zero to the Time of the Last Measurable Concentration (AUClast) | 2787 hour (h)*nanogram/millilitre (ng/mL) | Standard Deviation 1056 |
Secondary
Change From Baseline in Average Pain in the Daily Activities Scales of the Brief Pain Inventory - Short Form (BPI-SF)
Worst pain and Average pain are 'single question' scores from the BPI short form and may take any value from 0 to 10 (worst outcome). Interference Pain is the total score of 7 sub-scores, where each value may take any value from 0 to 10 (worst outcome). The range of the Interference Score can be from 0 to 70.
Time frame: Arm A: Screening, Day 1 of each cycle up to 9 months (Each cycle was 28 days in length); Arm B: Screening, Day 1 of each cycle up to 9 months (Each cycle was 21 days in length)
Population: Full analysis set consisted of all participants who received at least one (non-zero) dose of study treatment. The data for Arm A was not calculated because of only two participants in this arm due to which there will be a patient identification risk. Only safety data have been provided.~None of the 14 participants at Baseline answered the questionnaire at Cycle 1 Day 1 and, therefore, related statistics were not derived for this timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm B: AZD4635 + Durvalumab + Cabazitaxel | Change From Baseline in Average Pain in the Daily Activities Scales of the Brief Pain Inventory - Short Form (BPI-SF) | Baseline | 2.3 Score on a Scale | Standard Deviation 2.09 |
| Arm B: AZD4635 + Durvalumab + Cabazitaxel | Change From Baseline in Average Pain in the Daily Activities Scales of the Brief Pain Inventory - Short Form (BPI-SF) | Cycle 2 Day 1 | -1.3 Score on a Scale | Standard Deviation 1.19 |
| Arm B: AZD4635 + Durvalumab + Cabazitaxel | Change From Baseline in Average Pain in the Daily Activities Scales of the Brief Pain Inventory - Short Form (BPI-SF) | Cycle 3 Day 1 | 0.6 Score on a Scale | Standard Deviation 3.15 |
| Arm B: AZD4635 + Durvalumab + Cabazitaxel | Change From Baseline in Average Pain in the Daily Activities Scales of the Brief Pain Inventory - Short Form (BPI-SF) | Cycle 4 Day 1 | -0.9 Score on a Scale | Standard Deviation 1.27 |
| Arm B: AZD4635 + Durvalumab + Cabazitaxel | Change From Baseline in Average Pain in the Daily Activities Scales of the Brief Pain Inventory - Short Form (BPI-SF) | Cycle 5 Day 1 | -1.6 Score on a Scale | Standard Deviation 2.15 |
| Arm B: AZD4635 + Durvalumab + Cabazitaxel | Change From Baseline in Average Pain in the Daily Activities Scales of the Brief Pain Inventory - Short Form (BPI-SF) | Cycle 6 Day 1 | -1.4 Score on a Scale | Standard Deviation 1.51 |
| Arm B: AZD4635 + Durvalumab + Cabazitaxel | Change From Baseline in Average Pain in the Daily Activities Scales of the Brief Pain Inventory - Short Form (BPI-SF) | Cycle 7 Day 1 | 0.0 Score on a Scale | Standard Deviation 1.41 |
| Arm B: AZD4635 + Durvalumab + Cabazitaxel | Change From Baseline in Average Pain in the Daily Activities Scales of the Brief Pain Inventory - Short Form (BPI-SF) | Cycle 8 Day 1 | -0.8 Score on a Scale | Standard Deviation 1.47 |
| Arm B: AZD4635 + Durvalumab + Cabazitaxel | Change From Baseline in Average Pain in the Daily Activities Scales of the Brief Pain Inventory - Short Form (BPI-SF) | Cycle 9 Day 1 | -1.2 Score on a Scale | Standard Deviation 0.84 |
Secondary
Change From Baseline in Pain Interference in the Daily Activities Scales of the Brief Pain Inventory - Short Form (BPI-SF)
Worst pain and Average pain are 'single question' scores from the BPI short form and may take any value from 0 to 10 (worst outcome). Interference Pain is the total score of 7 sub-scores, where each value may take any value from 0 to 10 (worst outcome). The range of the Interference Score can be from 0 to 70.
Time frame: Arm A: Screening, Day 1 of each cycle up to 9 months (Each cycle was 28 days in length); Arm B: Screening, Day 1 of each cycle up to 9 months (Each cycle was 21 days in length)
Population: Full analysis set consisted of all participants who received at least one (non-zero) dose of study treatment. The data for Arm A was not calculated because of only two participants in this arm due to which there will be a patient identification risk. Only safety data have been provided.~None of the 14 participants at Baseline answered the questionnaire at Cycle 1 Day 1 and, therefore, related statistics were not derived for this timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm B: AZD4635 + Durvalumab + Cabazitaxel | Change From Baseline in Pain Interference in the Daily Activities Scales of the Brief Pain Inventory - Short Form (BPI-SF) | Cycle 4 Day 1 | 4.9 Score on a Scale | Standard Deviation 12.73 |
| Arm B: AZD4635 + Durvalumab + Cabazitaxel | Change From Baseline in Pain Interference in the Daily Activities Scales of the Brief Pain Inventory - Short Form (BPI-SF) | Baseline | 8.0 Score on a Scale | Standard Deviation 8.47 |
| Arm B: AZD4635 + Durvalumab + Cabazitaxel | Change From Baseline in Pain Interference in the Daily Activities Scales of the Brief Pain Inventory - Short Form (BPI-SF) | Cycle 2 Day 1 | 2.5 Score on a Scale | Standard Deviation 13.9 |
| Arm B: AZD4635 + Durvalumab + Cabazitaxel | Change From Baseline in Pain Interference in the Daily Activities Scales of the Brief Pain Inventory - Short Form (BPI-SF) | Cycle 3 Day 1 | 12.3 Score on a Scale | Standard Deviation 18.96 |
| Arm B: AZD4635 + Durvalumab + Cabazitaxel | Change From Baseline in Pain Interference in the Daily Activities Scales of the Brief Pain Inventory - Short Form (BPI-SF) | Cycle 5 Day 1 | 1.3 Score on a Scale | Standard Deviation 5.19 |
| Arm B: AZD4635 + Durvalumab + Cabazitaxel | Change From Baseline in Pain Interference in the Daily Activities Scales of the Brief Pain Inventory - Short Form (BPI-SF) | Cycle 6 Day 1 | 2.0 Score on a Scale | Standard Deviation 8.4 |
| Arm B: AZD4635 + Durvalumab + Cabazitaxel | Change From Baseline in Pain Interference in the Daily Activities Scales of the Brief Pain Inventory - Short Form (BPI-SF) | Cycle 7 Day 1 | 8.1 Score on a Scale | Standard Deviation 9.93 |
| Arm B: AZD4635 + Durvalumab + Cabazitaxel | Change From Baseline in Pain Interference in the Daily Activities Scales of the Brief Pain Inventory - Short Form (BPI-SF) | Cycle 8 Day 1 | 7.2 Score on a Scale | Standard Deviation 13.98 |
| Arm B: AZD4635 + Durvalumab + Cabazitaxel | Change From Baseline in Pain Interference in the Daily Activities Scales of the Brief Pain Inventory - Short Form (BPI-SF) | Cycle 9 Day 1 | 5.4 Score on a Scale | Standard Deviation 15.16 |
Secondary
Change From Baseline in the FACT Advanced Prostate Symptom Indext-6 (FAPSI-6), as Derived From 6 Items, the FAPSI-8 From 8 Items Within the FACT-P and the Prostate Cancer Symptoms (PCS), From the 12 Items in the Prostrate-specific Module of the FACT-P
The Functional Assessment of Cancer Therapy-Prostate (FACT-P) will be used to measure health related quality of life (HRQL) in men with prostate cancer. It consists of 4 subscales (physical, emotional, functional and social/family well-being) plus a 12-item prostate-specific module, the PCS subscale, which highlights concerns specific to participants with prostate cancer. FAPSI-6 is defined as a symptom score made up of 6 items from within the FACT-P (pain \[n = 3\], fatigue \[n = 1\], weight loss \[n = 1\], and concerns about the condition getting worse \[n = 1\]). Each question in the FACT-P questionnaires has a choice of 5 responses, Not at all, A little bit, Somewhat, Quite a bit and Very much. The scores range from 0 (Not at all) to 4 (Very much) for positively phrased questions. Negatively phrased questions have a reverse scoring, from 0 (Very much) to 4 (Not at all). This results in a consistent approach, where higher scores indicate a better quality of life.
Time frame: Arm A: Screening, Day 1 of each cycle up to 9 months (Each cycle was 28 days in length); Arm B: Screening, Day 1 of each cycle up to 9 months (Each cycle was 21 days in length)
Population: Full analysis set consisted of all participants who received at least one (non-zero) dose of study treatment. The data for Arm A was not calculated because of only two participants in this arm due to which there will be a patient identification risk.~None of the 10 participants at Baseline answered the questionnaire at Cycle 1 Day 1. Therefore, related statistics were not derived for this timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm B: AZD4635 + Durvalumab + Cabazitaxel | Change From Baseline in the FACT Advanced Prostate Symptom Indext-6 (FAPSI-6), as Derived From 6 Items, the FAPSI-8 From 8 Items Within the FACT-P and the Prostate Cancer Symptoms (PCS), From the 12 Items in the Prostrate-specific Module of the FACT-P | Baseline | 16.6 Score on a Scale | Standard Deviation 2.88 |
| Arm B: AZD4635 + Durvalumab + Cabazitaxel | Change From Baseline in the FACT Advanced Prostate Symptom Indext-6 (FAPSI-6), as Derived From 6 Items, the FAPSI-8 From 8 Items Within the FACT-P and the Prostate Cancer Symptoms (PCS), From the 12 Items in the Prostrate-specific Module of the FACT-P | Cycle 2 Day 1 | 1.9 Score on a Scale | Standard Deviation 1.68 |
| Arm B: AZD4635 + Durvalumab + Cabazitaxel | Change From Baseline in the FACT Advanced Prostate Symptom Indext-6 (FAPSI-6), as Derived From 6 Items, the FAPSI-8 From 8 Items Within the FACT-P and the Prostate Cancer Symptoms (PCS), From the 12 Items in the Prostrate-specific Module of the FACT-P | Cycle 3 Day 1 | -0.7 Score on a Scale | Standard Deviation 5.52 |
| Arm B: AZD4635 + Durvalumab + Cabazitaxel | Change From Baseline in the FACT Advanced Prostate Symptom Indext-6 (FAPSI-6), as Derived From 6 Items, the FAPSI-8 From 8 Items Within the FACT-P and the Prostate Cancer Symptoms (PCS), From the 12 Items in the Prostrate-specific Module of the FACT-P | Cycle 4 Day 1 | -0.1 Score on a Scale | Standard Deviation 3.34 |
| Arm B: AZD4635 + Durvalumab + Cabazitaxel | Change From Baseline in the FACT Advanced Prostate Symptom Indext-6 (FAPSI-6), as Derived From 6 Items, the FAPSI-8 From 8 Items Within the FACT-P and the Prostate Cancer Symptoms (PCS), From the 12 Items in the Prostrate-specific Module of the FACT-P | Cycle 5 Day 1 | 0.6 Score on a Scale | Standard Deviation 3.36 |
| Arm B: AZD4635 + Durvalumab + Cabazitaxel | Change From Baseline in the FACT Advanced Prostate Symptom Indext-6 (FAPSI-6), as Derived From 6 Items, the FAPSI-8 From 8 Items Within the FACT-P and the Prostate Cancer Symptoms (PCS), From the 12 Items in the Prostrate-specific Module of the FACT-P | Cycle 6 Day 1 | 1.5 Score on a Scale | Standard Deviation 1.38 |
| Arm B: AZD4635 + Durvalumab + Cabazitaxel | Change From Baseline in the FACT Advanced Prostate Symptom Indext-6 (FAPSI-6), as Derived From 6 Items, the FAPSI-8 From 8 Items Within the FACT-P and the Prostate Cancer Symptoms (PCS), From the 12 Items in the Prostrate-specific Module of the FACT-P | Cycle 7 Day 1 | 0.0 Score on a Scale | Standard Deviation 3.92 |
| Arm B: AZD4635 + Durvalumab + Cabazitaxel | Change From Baseline in the FACT Advanced Prostate Symptom Indext-6 (FAPSI-6), as Derived From 6 Items, the FAPSI-8 From 8 Items Within the FACT-P and the Prostate Cancer Symptoms (PCS), From the 12 Items in the Prostrate-specific Module of the FACT-P | Cycle 8 Day 1 | -1.8 Score on a Scale | Standard Deviation 4.15 |
| Arm B: AZD4635 + Durvalumab + Cabazitaxel | Change From Baseline in the FACT Advanced Prostate Symptom Indext-6 (FAPSI-6), as Derived From 6 Items, the FAPSI-8 From 8 Items Within the FACT-P and the Prostate Cancer Symptoms (PCS), From the 12 Items in the Prostrate-specific Module of the FACT-P | Cycle 9 Day 1 | -3.0 Score on a Scale | Standard Deviation 4.55 |
Secondary
Change From Baseline in Worst Pain in the Daily Activities Scales of the Brief Pain Inventory - Short Form (BPI-SF)
Worst pain and Average pain are 'single question' scores from the BPI short form and may take any value from 0 to 10 (worst outcome). Interference Pain is the total score of 7 sub-scores, where each value may take any value from 0 to 10 (worst outcome). The range of the Interference Score can be from 0 to 70.
Time frame: Arm A: Screening, Day 1 of each cycle up to 9 months (Each cycle was 28 days in length); Arm B: Screening, Day 1 of each cycle up to 9 months (Each cycle was 21 days in length)
Population: Full analysis set consisted of all participants who received at least one (non-zero) dose of study treatment. The data for Arm A was not calculated because of only two participants in this arm due to which there will be a patient identification risk. Only safety data have been provided.~None of the 14 participants at Baseline answered the questionnaire at Cycle 1 Day 1. Therefore, related statistics were not derived for this timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm B: AZD4635 + Durvalumab + Cabazitaxel | Change From Baseline in Worst Pain in the Daily Activities Scales of the Brief Pain Inventory - Short Form (BPI-SF) | Baseline | 3.4 Score on a Scale | Standard Deviation 2.44 |
| Arm B: AZD4635 + Durvalumab + Cabazitaxel | Change From Baseline in Worst Pain in the Daily Activities Scales of the Brief Pain Inventory - Short Form (BPI-SF) | Cycle 2 Day 1 | -1.6 Score on a Scale | Standard Deviation 2.94 |
| Arm B: AZD4635 + Durvalumab + Cabazitaxel | Change From Baseline in Worst Pain in the Daily Activities Scales of the Brief Pain Inventory - Short Form (BPI-SF) | Cycle 3 Day 1 | -0.3 Score on a Scale | Standard Deviation 4.4 |
| Arm B: AZD4635 + Durvalumab + Cabazitaxel | Change From Baseline in Worst Pain in the Daily Activities Scales of the Brief Pain Inventory - Short Form (BPI-SF) | Cycle 4 Day 1 | -1.6 Score on a Scale | Standard Deviation 2.88 |
| Arm B: AZD4635 + Durvalumab + Cabazitaxel | Change From Baseline in Worst Pain in the Daily Activities Scales of the Brief Pain Inventory - Short Form (BPI-SF) | Cycle 5 Day 1 | -2.1 Score on a Scale | Standard Deviation 3.58 |
| Arm B: AZD4635 + Durvalumab + Cabazitaxel | Change From Baseline in Worst Pain in the Daily Activities Scales of the Brief Pain Inventory - Short Form (BPI-SF) | Cycle 6 Day 1 | -1.9 Score on a Scale | Standard Deviation 3 |
| Arm B: AZD4635 + Durvalumab + Cabazitaxel | Change From Baseline in Worst Pain in the Daily Activities Scales of the Brief Pain Inventory - Short Form (BPI-SF) | Cycle 7 Day 1 | 1.0 Score on a Scale | Standard Deviation 1.85 |
| Arm B: AZD4635 + Durvalumab + Cabazitaxel | Change From Baseline in Worst Pain in the Daily Activities Scales of the Brief Pain Inventory - Short Form (BPI-SF) | Cycle 8 Day 1 | -1.7 Score on a Scale | Standard Deviation 2.66 |
| Arm B: AZD4635 + Durvalumab + Cabazitaxel | Change From Baseline in Worst Pain in the Daily Activities Scales of the Brief Pain Inventory - Short Form (BPI-SF) | Cycle 9 Day 1 | -0.2 Score on a Scale | Standard Deviation 2.17 |
Secondary
Maximum Observed Plasma Concentration (Cmax)
Investigate the PK of AZD4635 when given in combination with durvalumab, and when given in combination with durvalumab plus cabazitaxel.
Time frame: Arm A:Cycle 1 to 3, and Cycle 4 onwards, and 90-day follow-up (FU) visit up to 14 months [Each cycle was 28 days in length];Arm B: Cycle 1 to 7 and Cycle 11 onwards, and 90-day FU up to 14 months (Cycle 1 to Cycle 10 = 21 days, Cycle 11 onwards = 28 days)
Population: The pharmacokinetics (PK) analysis set consisted of dosed participants for whom an adequate PK profile was obtained. The data for Arm A was not calculated because of only two participants in this arm due to which there will be a patient identification risk.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm B: AZD4635 + Durvalumab + Cabazitaxel | Maximum Observed Plasma Concentration (Cmax) | 483.0 nanogram/millilitre (ng/mL) | Standard Deviation 231.1 |
Secondary
Number of Participants Who Progressed Based on BPI-SF Item 3
Pain progression was assessed using BPI-SF.
Time frame: Arm A: Screening, Day 1 of each cycle up to 12 months (Each cycle was 28 days in length); Arm B: Screening, Day 1 of each cycle up to 12 months (Cycle 1 to Cycle 10 = 21 days, Cycle 11 onwards = 28 days)
Population: Full analysis set consisted of all participants who received at least one (non-zero) dose of study treatment. The data for Arm A was not calculated because of only two participants in this arm due to which there will be a patient identification risk.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm B: AZD4635 + Durvalumab + Cabazitaxel | Number of Participants Who Progressed Based on BPI-SF Item 3 | 1 Participants |
Secondary
Number of Participants With Objective Response in Subjects With MCRPC Who Received AZD4635 Plus Durvalumab Plus Cabazitaxel
Confirmed ORR was defined as the proportion of participants with a confirmed complete response (CR) or partial response (PR) using overall radiographic response assessed by RECIST v1.1 and PCWG-3 criteria (bone), and was based on a subset of all treated participants with measurable disease at baseline per the site Investigator.
Time frame: From first dose to first documented progression or death from any cause (whichever comes first), up to two years
Population: Evaluable for efficacy set consisted of dosed patients with a baseline tumour assessment. The data for Arm A was not calculated because of only two participants in this arm due to which there will be a patient identification risk.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm B: AZD4635 + Durvalumab + Cabazitaxel | Number of Participants With Objective Response in Subjects With MCRPC Who Received AZD4635 Plus Durvalumab Plus Cabazitaxel | 2 Participants |
Secondary
Number of Participants With Prostate-specifin Antigen (PSA50) Response in Subjects With MCRPC Who Received AZD4635 Plus Durvalumab Plus Cabazitaxel
Confirmed PSA50 response is defined as the proportion of participants who achieved a ≥50% decrease in PSA from baseline to the lowest post-baseline PSA, confirmed by a consecutive PSA at least 3 weeks later and was based on PSA evaluable participants (dosed participants with an abnormal baseline PSA \[≥1 ng/mL\]).
Time frame: Arm A: Screening, Day 1 of each cycle up to 11 months (Each cycle was 28 days in length); Arm B: Screening, Day 1 of each cycle up to 11 months (Cycle 1 to Cycle 10 = 21 days, Cycle 11 onwards = 28 days)
Population: PSA evaluable analysis set consisted of dosed participants with an abnormal baseline PSA (=1ng/mL). The data for Arm A was not calculated because of only two participants in this arm due to which there will be a patient identification risk.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm B: AZD4635 + Durvalumab + Cabazitaxel | Number of Participants With Prostate-specifin Antigen (PSA50) Response in Subjects With MCRPC Who Received AZD4635 Plus Durvalumab Plus Cabazitaxel | 5 Participants |
Secondary
Number of Subjects With Serious and Non-serious Adverse Events
Safety and tolerability of each treatment regimen were assessed in participants with mCRPC.
Time frame: Arm A: From Screening up to 14 months (Each cycle was 28 days in length); Arm B: From Screening up to 14 months (Cycle 1 to Cycle 10 was 21 days in length, and Cycle 11 onwards was 28 days in length)
Population: The safety analysis set consisted of all participants who received at least 1 dose of study drug. The data for Arm A was not calculated because of only two participants in this arm due to which there will be a patient identification risk.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm B: AZD4635 + Durvalumab + Cabazitaxel | Number of Subjects With Serious and Non-serious Adverse Events | Any Adverse Event (AE) | 28 Participants |
| Arm B: AZD4635 + Durvalumab + Cabazitaxel | Number of Subjects With Serious and Non-serious Adverse Events | Any AE possibly related to treatment | 28 Participants |
| Arm B: AZD4635 + Durvalumab + Cabazitaxel | Number of Subjects With Serious and Non-serious Adverse Events | Any AE possibly related to AZD4635 | 23 Participants |
| Arm B: AZD4635 + Durvalumab + Cabazitaxel | Number of Subjects With Serious and Non-serious Adverse Events | Any AE possibly related to Durvalumab | 20 Participants |
| Arm B: AZD4635 + Durvalumab + Cabazitaxel | Number of Subjects With Serious and Non-serious Adverse Events | Any AE possibly related to Cabazitaxel | 28 Participants |
| Arm B: AZD4635 + Durvalumab + Cabazitaxel | Number of Subjects With Serious and Non-serious Adverse Events | Any AE of CTCAE grade 3 or higher | 24 Participants |
| Arm B: AZD4635 + Durvalumab + Cabazitaxel | Number of Subjects With Serious and Non-serious Adverse Events | Any AE of CTCAE grade 3 or higher, possibly related to treatment | 20 Participants |
| Arm B: AZD4635 + Durvalumab + Cabazitaxel | Number of Subjects With Serious and Non-serious Adverse Events | Any AE of CTCAE grade 3 or higher possibly related to AZD4635 | 9 Participants |
| Arm B: AZD4635 + Durvalumab + Cabazitaxel | Number of Subjects With Serious and Non-serious Adverse Events | Any AE of CTCAE grade 3 or higher possibly related to Durvalumab | 9 Participants |
| Arm B: AZD4635 + Durvalumab + Cabazitaxel | Number of Subjects With Serious and Non-serious Adverse Events | Any AE of CTCAE grade 3 or higher possibly related to Cabazitaxel | 19 Participants |
| Arm B: AZD4635 + Durvalumab + Cabazitaxel | Number of Subjects With Serious and Non-serious Adverse Events | Any Adverse Event of Special Interest (AESI) for Durvalumab | 17 Participants |
| Arm B: AZD4635 + Durvalumab + Cabazitaxel | Number of Subjects With Serious and Non-serious Adverse Events | Any possibly related AESI for Durvalumab | 10 Participants |
| Arm B: AZD4635 + Durvalumab + Cabazitaxel | Number of Subjects With Serious and Non-serious Adverse Events | Any AE with outcome = death | 2 Participants |
| Arm B: AZD4635 + Durvalumab + Cabazitaxel | Number of Subjects With Serious and Non-serious Adverse Events | Any AE with outcome = death possibly related to treatment | 1 Participants |
| Arm B: AZD4635 + Durvalumab + Cabazitaxel | Number of Subjects With Serious and Non-serious Adverse Events | Any Serious Adverse Event (SAE) (including events with outcome = death) | 19 Participants |
| Arm B: AZD4635 + Durvalumab + Cabazitaxel | Number of Subjects With Serious and Non-serious Adverse Events | Any SAE (including events with outcome = death) possibly related to treatment | 12 Participants |
| Arm B: AZD4635 + Durvalumab + Cabazitaxel | Number of Subjects With Serious and Non-serious Adverse Events | Any SAE leading to discontinuation of AZD4635 | 4 Participants |
| Arm B: AZD4635 + Durvalumab + Cabazitaxel | Number of Subjects With Serious and Non-serious Adverse Events | Any SAE leading to discontinuation of AZD4635 possibly related to AZD4635 | 1 Participants |
| Arm B: AZD4635 + Durvalumab + Cabazitaxel | Number of Subjects With Serious and Non-serious Adverse Events | Any AE leading to discontinuation of AZD4635 | 5 Participants |
| Arm B: AZD4635 + Durvalumab + Cabazitaxel | Number of Subjects With Serious and Non-serious Adverse Events | Any AE leading to dose reduction of AZD4635 | 4 Participants |
| Arm B: AZD4635 + Durvalumab + Cabazitaxel | Number of Subjects With Serious and Non-serious Adverse Events | Any AE leading to dose interruption of AZD4635 | 15 Participants |
| Arm B: AZD4635 + Durvalumab + Cabazitaxel | Number of Subjects With Serious and Non-serious Adverse Events | Any AE leading to discontinuation of Durvalumab | 4 Participants |
| Arm B: AZD4635 + Durvalumab + Cabazitaxel | Number of Subjects With Serious and Non-serious Adverse Events | Any AE leading to dose interruption of Durvalumab | 5 Participants |
| Arm B: AZD4635 + Durvalumab + Cabazitaxel | Number of Subjects With Serious and Non-serious Adverse Events | Any AE leading to discontinuation of Cabazitaxel | 7 Participants |
| Arm B: AZD4635 + Durvalumab + Cabazitaxel | Number of Subjects With Serious and Non-serious Adverse Events | Any AE leading to dose reduction of Cabazitaxel | 4 Participants |
| Arm B: AZD4635 + Durvalumab + Cabazitaxel | Number of Subjects With Serious and Non-serious Adverse Events | Any AE leading to dose interruption of Cabazitaxel | 8 Participants |
| Arm B: AZD4635 + Durvalumab + Cabazitaxel | Number of Subjects With Serious and Non-serious Adverse Events | Any other significant AEs | 0 Participants |
Secondary
Overall Survival (OS) in Each Arm Separately to Determine the Efficacy of AZD4635 Plus Durvalumab and of AZD4635 Plus Durvalumab Plus Cabazitaxel in Participants With mCRPC
OS was defined as the time from first dose until death due to any cause regardless of whether the participant withdrew from study treatment or received another anti-cancer therapy.
Time frame: Arm A and B: Every 90 days from the last dose of study drug up to 2 years
Population: Evaluable for efficacy set consisted of dosed patients with a baseline tumour assessment. The data for Arm A was not calculated because of only two participants in this arm due to which there will be a patient identification risk.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm B: AZD4635 + Durvalumab + Cabazitaxel | Overall Survival (OS) in Each Arm Separately to Determine the Efficacy of AZD4635 Plus Durvalumab and of AZD4635 Plus Durvalumab Plus Cabazitaxel in Participants With mCRPC | NA months |
Secondary
rPFS by Adenosine (ADO) Signalling Gene Expression in High and Low Subgroups to Determine the Efficacy of AZD4635 Plus Durvalumab Plus Cabazitaxel in Participants With mCRPC
rPFS was defined as the time from first dose to radiographic progression, assessed by the Investigator per RECIST 1.1 (soft tissue) and PCWG3 criteria (bone) or death from any cause, whichever occurred first.
Time frame: From first dose to first documented progression or death from any cause (whichever comes first), up to two years
Population: Evaluable for efficacy set consisted of dosed patients with a baseline tumour assessment. The data for Arm A was not calculated because of only two participants in this arm due to which there will be a patient identification risk. The analysis of rPFS by ADO was not done.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm B: AZD4635 + Durvalumab + Cabazitaxel | rPFS by Adenosine (ADO) Signalling Gene Expression in High and Low Subgroups to Determine the Efficacy of AZD4635 Plus Durvalumab Plus Cabazitaxel in Participants With mCRPC | High ADO | 14 Participants |
| Arm B: AZD4635 + Durvalumab + Cabazitaxel | rPFS by Adenosine (ADO) Signalling Gene Expression in High and Low Subgroups to Determine the Efficacy of AZD4635 Plus Durvalumab Plus Cabazitaxel in Participants With mCRPC | Low ADO | 13 Participants |
Secondary
Terminal Half-life (t1/2λz)
Investigated the PK of AZD4635 when given in combination with durvalumab, and when given in combination with durvalumab plus cabazitaxel.
Time frame: Arm A:Cycle 1 to 3, and Cycle 4 onwards, and 90-day follow-up (FU) visit up to 14 months [Each cycle was 28 days in length];Arm B: Cycle 1 to 7 and Cycle 11 onwards, and 90-day FU up to 14 months (Cycle 1 to Cycle 10 = 21 days, Cycle 11 onwards = 28 days)
Population: The PK analysis set consisted of dosed participants for whom an adequate PK profile was obtained. The data for Arm A was not calculated because of only two participants in this arm due to which there will be a patient identification risk.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm B: AZD4635 + Durvalumab + Cabazitaxel | Terminal Half-life (t1/2λz) | 8.87 hour (h) | Standard Deviation 4.82 |