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| ID | Type | Description | Link |
|---|---|---|---|
| 2020-000209-10 | EudraCT Number |
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| Name | Class |
|---|---|
| Parexel | INDUSTRY |
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This is a Phase II, international, open-label, two-arm, non-randomised study of AZD4635 in participants with metastatic castration-resistant prostate cancer (mCRPC).
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm A: AZD4635 + durvalumab | Experimental | AZD4635 plus durvalumab (Arm A) will consist of participants with mCRPC previously treated with one or more approved NHAs (eg, abiraterone acetate, enzalutamide, apalutamide and/or darolutamide), and one or more taxanes, or participants who are taxane ineligible. |
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| Arm B: AZD4635 + durvalumab + cabazitaxel | Experimental | AZD4635 plus durvalumab plus cabazitaxel (Arm B) will consist of participants with mCRPC previously treated with docetaxel and one prior NHA (either abiraterone acetate or enzalutamide but not both (prior apalutamide is not allowed in Arm B). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| AZD4635 | Drug | Subjects will receive AZD4635 orally daily |
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| Measure | Description | Time Frame |
|---|---|---|
| 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. | From first dose to first documented progression or death from any cause (whichever comes first) (approximately 1 year) |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | From first dose to first documented progression or death from any cause (whichever comes first), up to two years |
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Inclusion Criteria:
Histologically confirmed adenocarcinoma of the prostate.
Known castrate-resistant disease.
Evidence of disease progression ≤6 months.
Body weight >30 kg at screening.
Willingness to adhere to the study treatment-specific contraception requirements.
Adequate bone marrow reserve and organ function.
Adequate organ function for Arm A as demonstrated by all of the following laboratory values:
Participants in Arm A must have received the following prior therapy:
Adequate organ function for Arm B as demonstrated by all of the following laboratory values:
Participants in Arm B must have received the following prior therapy:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Christopher J Sweeney, MBBS | Dana-Farber Cancer Institute | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Sacramento | California | 95817 | United States | ||
| Research Site |
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| Label | URL |
|---|---|
| Related Info | View source |
| Related Info | View source |
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Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
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 were enrolled in this study from 04-August-2020 to 08-August-2022.
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| ID | Title | Description |
|---|---|---|
| FG000 | Arm A: AZD4635 + Durvalumab | Participants received AZD4635 Dose A orally daily, and durvalumab Dose B intravenously every 4 weeks. |
| FG001 | Arm B: AZD4635 + Durvalumab + Cabazitaxel |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Nov 24, 2020 | Oct 28, 2022 |
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| Durvalumab | Drug | Subjects will receive intravenous durvalumab every 4 weeks for Arm A and every 3 weeks for Arm B. |
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| Cabazitaxel | Drug | Subjects will receive intravenous cabazitaxel every 3 weeks |
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| 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. | Arm A and B: Every 90 days from the last dose of study drug up to 2 years |
| 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. | From first dose to first documented progression or death from any cause (whichever comes first), up to two years |
| 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]). | 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) |
| 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. | 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) |
| 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. | 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) |
| 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. | 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) |
| Number of Participants Who Progressed Based on BPI-SF Item 3 | Pain progression was assessed using BPI-SF. | 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) |
| 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. | 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) |
| 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. | 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) |
| 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. | 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) |
| 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. | 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) |
| 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. | 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) |
| 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. | 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) |
| 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. | 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) |
| Number of Subjects With Serious and Non-serious Adverse Events | Safety and tolerability of each treatment regimen were assessed in participants with mCRPC. | 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) |
| Tampa |
| Florida |
| 33612 |
| United States |
| Research Site | Atlanta | Georgia | 30318 | United States |
| Research Site | St Louis | Missouri | 63110 | United States |
| Research Site | Winston-Salem | North Carolina | 27157 | United States |
| Research Site | Brasschaat | 2930 | Belgium |
| Research Site | Ghent | 9000 | Belgium |
| Research Site | Bordeaux | 33076 | France |
| Research Site | Villejuif | 94805 | France |
| Research Site | Goyang-si | 10408 | South Korea |
| Research Site | Seoul | 06351 | South Korea |
| Research Site | Seoul | 06591 | South Korea |
| Research Site | Barcelona | 08041 | Spain |
| Research Site | Barcelona | 8035 | Spain |
| Research Site | Hospitalet deLlobregat | 08907 | Spain |
| Research Site | Madrid | 28034 | Spain |
| Related Info | View source |
Participants received AZD4635 Dose A orally daily, durvalumab Dose B intravenously (IV) every 3 weeks (Q3W), and cabazitaxel Dose C IV Q3W
| COMPLETED |
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| NOT COMPLETED |
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Safety analysis set consisted of all patients who received at least one 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.
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| ID | Title | Description |
|---|---|---|
| BG000 | Arm A: AZD4635 + Durvalumab | Participants received AZD4635 Dose A orally daily, and durvalumab Dose B intravenously every 4 weeks. |
| BG001 | 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 |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 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. | Mean | Standard Deviation | years |
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| Sex/Gender, Customized | 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. | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | 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 number analyzed in the row differs from the overall value as efficacy for low number of participants were not presented. | Count of Participants | Participants |
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| Race (NIH/OMB) | 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. | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
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| 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. | 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. | Posted | Median | 95% Confidence Interval | months | From first dose to first documented progression or death from any cause (whichever comes first) (approximately 1 year) |
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| 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. | 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. | Posted | Count of Participants | Participants | From first dose to first documented progression or death from any cause (whichever comes first), up to two years |
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| 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. | 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. | Posted | Median | 95% Confidence Interval | months | Arm A and B: Every 90 days from the last dose of study drug up to 2 years |
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| 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. | 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. | Posted | Number | Participants | From first dose to first documented progression or death from any cause (whichever comes first), up to two years |
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| 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]). | 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. | Posted | Count of Participants | Participants | 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) |
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| 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. | 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. | Posted | Mean | Standard Deviation | Score on a Scale | 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) |
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| 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. | 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. | Posted | Mean | Standard Deviation | Score on a Scale | 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) |
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| 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. | 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. | Posted | Mean | Standard Deviation | Score on a Scale | 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) |
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| Secondary | Number of Participants Who Progressed Based on BPI-SF Item 3 | Pain progression was assessed using BPI-SF. | 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. | Posted | Number | Participants | 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) |
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| 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. | 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. | Posted | Mean | Standard Deviation | Score on a Scale | 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) |
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| 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. | 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. | Posted | Mean | Standard Deviation | nanogram/millilitre (ng/mL) | 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) |
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| 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. | 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. | Posted | Mean | Standard Deviation | hour (h) | 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) |
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| 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. | 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. | Posted | Mean | Standard Deviation | hour (h)*nanogram/millilitre (ng/mL) | 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) |
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| 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. | 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. | Posted | Mean | Standard Deviation | hour (h)*nanogram/millilitre (ng/mL) | 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) |
|
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| 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. | 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. | Posted | Mean | Standard Deviation | hour (h)*nanogram/millilitre (ng/mL) | 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) |
|
| |||||||||||||||||||||||||||||
| 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. | 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. | Posted | Mean | Standard Deviation | Litre | 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) |
|
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| Secondary | Number of Subjects With Serious and Non-serious Adverse Events | Safety and tolerability of each treatment regimen were assessed in participants with mCRPC. | 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. | Posted | Count of Participants | Participants | 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) |
|
|
All-Cause Mortality: Up to 2 years; Serious and/or other adverse events: From Screening up to 14 months (Each cycle was 28 days in length) for Arm A and 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) for Arm B.
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Arm A: AZD4635 + Durvalumab | Participants received AZD4635 Dose A orally daily, and durvalumab Dose B intravenously every 4 weeks. | 2 | 2 | 2 | 2 | 2 | 2 |
| EG001 | 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 | 7 | 28 | 19 | 28 | 28 | 28 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abscess neck | Infections and infestations | MedDRA v24.1 | Non-systematic Assessment |
| |
| Diverticulitis | Infections and infestations | MedDRA v24.1 | Non-systematic Assessment |
| |
| Ureteritis | Infections and infestations | MedDRA v24.1 | Non-systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA v24.1 | Non-systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | MedDRA v24.1 | Non-systematic Assessment |
| |
| Febrile Neutropenia | Blood and lymphatic system disorders | MedDRA v24.1 | Non-systematic Assessment |
| |
| Decreased Appetite | Metabolism and nutrition disorders | MedDRA v24.1 | Non-systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA v24.1 | Non-systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA v24.1 | Non-systematic Assessment |
| |
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA v24.1 | Non-systematic Assessment |
| |
| Colitis | Gastrointestinal disorders | MedDRA v24.1 | Non-systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA v24.1 | Non-systematic Assessment |
| |
| Dysphagia | Gastrointestinal disorders | MedDRA v24.1 | Non-systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA v24.1 | Non-systematic Assessment |
| |
| Rectal Haemorrhage | Gastrointestinal disorders | MedDRA v24.1 | Non-systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA v24.1 | Non-systematic Assessment |
| |
| Cholecystitis | Hepatobiliary disorders | MedDRA v24.1 | Non-systematic Assessment |
| |
| Cholecystitis Acute | Hepatobiliary disorders | MedDRA v24.1 | Non-systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA v24.1 | Non-systematic Assessment |
| |
| Myositis | Musculoskeletal and connective tissue disorders | MedDRA v24.1 | Non-systematic Assessment |
| |
| Cystitis Haemorrhagic | Renal and urinary disorders | MedDRA v24.1 | Non-systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | MedDRA v24.1 | Non-systematic Assessment |
| |
| Hydronephrosis | Renal and urinary disorders | MedDRA v24.1 | Non-systematic Assessment |
| |
| Urinary Retention | Renal and urinary disorders | MedDRA v24.1 | Non-systematic Assessment |
| |
| Malaise | General disorders | MedDRA v24.1 | Non-systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA v24.1 | Non-systematic Assessment |
| |
| Neutrophil Count Decreased | Investigations | MedDRA v24.1 | Non-systematic Assessment |
| |
| Acute Post Hemorrhagic Anemia | Blood and lymphatic system disorders | MedDRA v24.1 | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Urinary tract infection | Infections and infestations | MedDRA v24.1 | Non-systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | MedDRA v24.1 | Non-systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA v24.1 | Non-systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA v24.1 | Non-systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA v24.1 | Non-systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA v24.1 | Non-systematic Assessment |
| |
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA v24.1 | Non-systematic Assessment |
| |
| Hyperuricaemia | Metabolism and nutrition disorders | MedDRA v24.1 | Non-systematic Assessment |
| |
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA v24.1 | Non-systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA v24.1 | Non-systematic Assessment |
| |
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA v24.1 | Non-systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA v24.1 | Non-systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA v24.1 | Non-systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA v24.1 | Non-systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | MedDRA v24.1 | Non-systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA v24.1 | Non-systematic Assessment |
| |
| Neuropathy peripheral | Nervous system disorders | MedDRA v24.1 | Non-systematic Assessment |
| |
| Peripheral sensory neuropathy | Nervous system disorders | MedDRA v24.1 | Non-systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA v24.1 | Non-systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA v24.1 | Non-systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA v24.1 | Non-systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA v24.1 | Non-systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA v24.1 | Non-systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA v24.1 | Non-systematic Assessment |
| |
| Dry mouth | Gastrointestinal disorders | MedDRA v24.1 | Non-systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA v24.1 | Non-systematic Assessment |
| |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA v24.1 | Non-systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA v24.1 | Non-systematic Assessment |
| |
| Oral pain | Gastrointestinal disorders | MedDRA v24.1 | Non-systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA v24.1 | Non-systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA v24.1 | Non-systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA v24.1 | Non-systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA v24.1 | Non-systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA v24.1 | Non-systematic Assessment |
| |
| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA v24.1 | Non-systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA v24.1 | Non-systematic Assessment |
| |
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA v24.1 | Non-systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA v24.1 | Non-systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA v24.1 | Non-systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | MedDRA v24.1 | Non-systematic Assessment |
| |
| Urinary retention | Renal and urinary disorders | MedDRA v24.1 | Non-systematic Assessment |
| |
| Reproductive system and breast disorders | Reproductive system and breast disorders | MedDRA v24.1 | Non-systematic Assessment |
| |
| Asthenia | General disorders | MedDRA v24.1 | Non-systematic Assessment |
| |
| Chills | General disorders | MedDRA v24.1 | Non-systematic Assessment |
| |
| Fatigue | General disorders | MedDRA v24.1 | Non-systematic Assessment |
| |
| Non-cardiac chest pain | General disorders | MedDRA v24.1 | Non-systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA v24.1 | Non-systematic Assessment |
| |
| Pain | General disorders | MedDRA v24.1 | Non-systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA v24.1 | Non-systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA v24.1 | Non-systematic Assessment |
| |
| Amylase increased | Investigations | MedDRA v24.1 | Non-systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA v24.1 | Non-systematic Assessment |
| |
| Blood alkaline phosphatase increased | Investigations | MedDRA v24.1 | Non-systematic Assessment |
| |
| Blood lactate dehydrogenase increased | Investigations | MedDRA v24.1 | Non-systematic Assessment |
| |
| Lipase increased | Investigations | MedDRA v24.1 | Non-systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA v24.1 | Non-systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA v24.1 | Non-systematic Assessment |
| |
| White blood cell count decreased | Investigations | MedDRA v24.1 | Non-systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA v24.1 | Non-systematic Assessment |
|
This document contains trade secrets and confidential commercial information, disclosure of which is prohibited without providing advance notice to AstraZeneca and opportunity to object.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Global Clinical Head | AstraZeneca Clinical Study Information Center | 1-877-240-94 79 | information.center@astrazeneca.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Apr 20, 2022 | Oct 28, 2022 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D011471 | Prostatic Neoplasms |
| ID | Term |
|---|---|
| D005834 | Genital Neoplasms, Male |
| D014565 | Urogenital Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D005832 | Genital Diseases, Male |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D011469 | Prostatic Diseases |
| D052801 | Male Urogenital Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C000613593 | durvalumab |
| C552428 | cabazitaxel |
Not provided
Not provided
Not provided
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| Participants |
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| Participants |
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| Units | Counts |
|---|---|
| Participants |
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| OG000 |
| Arm A: AZD4635 + Durvalumab |
Participants received AZD4635 Dose A orally daily, and durvalumab Dose B intravenously every 4 weeks. |
| OG001 | 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 |
|
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| Participants |
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| Participants |
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| Participants |
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| Participants |
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