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| ID | Type | Description | Link |
|---|---|---|---|
| 2025-524171-22-00 | EU Trial (CTIS) Number |
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The purpose of this modular, first trial in human study is to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of ascending dose levels (DLs) of AZD4956 monotherapy and in combination with other anti-cancer agents in participants with advanced/metastatic solid tumours with homologous recombination repair (HRR) deficiencies.
The study consists of individual modules each evaluating the safety and tolerability of AZD4956 dosed as monotherapy, or with a specific combination partner. There are following 2 modules -
Each module may further contain 2 parts-
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Module 1 Part A: AZD4956 monotherapy (Dose escalation) | Experimental | Participants will receive AZD4956 as monotherapy at ascending dose levels. |
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| Module 2 Part A: AZD4956 + saruparib (Dose escalation) | Experimental | Participants will receive AZD4956 at ascending dose levels in combination with saruparib. |
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| Module 2 Part A Optional PD backfill cohort: AZD4956 + saruparib | Experimental | Participants will receive AZD4956 in combination with saruparib. |
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| Module 2 Part A Optional PD backfill cohort: Saruparib monotherapy | Experimental | Participants will receive saruparib monotherapy. |
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| Module 2 Part A Optional non-PD backfill cohort: AZD4956 + saruparib | Experimental | Participants with metastatic castrate resistant prostate cancer (mCRPC) will receive AZD4956 in combination with saruparib. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| AZD4956 | Drug | AZD4956 will be administered orally. |
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| Measure | Description | Time Frame |
|---|---|---|
| Parts A and B: Number of participants with adverse events (AEs) and serious adverse events (SAEs) | To assess the safety and tolerability of AZD4956 monotherapy and in combination with anti-cancer agent(s). | From Screening (Day -28) to follow-up (up to 3.5 years) |
| Part B: Progression free survival (PFS) | PFS is defined as the time from the start of treatment until the date of objective disease progression or death (by any cause in the absence of progression), regardless of whether the participants withdraw from study treatment or receive another anti-cancer therapy prior to progression. | Up to 3.5 years |
| Part A - Number of participants with dose-limiting toxicities (DLTs) | To assess the safety and tolerability of AZD4956 monotherapy and in combination with anti-cancer agent(s). | Up to 28 days |
| Measure | Description | Time Frame |
|---|---|---|
| Objective response (OR) | OR is defined as if a participant achieves a best overall response (BOR) of confirmed complete response (CR) or partial response (PR), as assessed by the investigator, according to response evaluation criteria in solid tumours (RECIST) v1.1 criterion. | Up to 3.5 years |
| Duration of response (DoR) |
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Core Inclusion Criteria:
Module 1 Inclusion Criteria:
Module 2 Inclusion Criteria:
Part A (AZD4956 in Combination with Saruparib Dose Escalation) and Part A-PD (PD Backfill Cohorts):
Participants must have one of the following conditions-
Participants must have evaluable disease.
Participants in PD backfill cohorts must not have received prior therapy with a PARPi-based regimen (either as a treatment or as maintenance).
Part A (PD Backfill Cohorts) - Participants Undergoing Paired Biopsies:
- Participants must have a tumour suitable for biopsy.
Part A-Non-PD (Non-PD Backfill Cohorts) and Part B (Dose Expansion Cohorts):
Core Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| AstraZeneca Clinical Study Information Center | Contact | 1-877-240-9479 | information.center@astrazeneca.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Not yet recruiting | New York | New York | 10065 | United States | |
| Research Site |
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests 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.
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AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA 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 anonymized individual patient-level data via secure research environment Vivli.org. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.
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| Module 2 Part B: AZD4956 + saruparib (Dose expansion) | Experimental | Participants will receive AZD4956 in combination with saruparib. |
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| Saruparib | Drug | Saruparib will be administered orally. |
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DoR is defined as the time from the date of first documented OR assessed by RECIST v1.1, in the absence of progression on bone scan assessed by prostate cancer working group 3 (PCWG3), until the date of documented disease progression or death in the absence of disease progression. |
| Up to 3.5 years |
| Best Overall Response (BOR) | To assess the preliminary anti-tumour activity of AZD4956 monotherapy and in combination with anti-cancer agent(s). | Up to 3.5 years |
| Time to response (TTR) | TTR is defined as the time from the date of first dose of study intervention until the date of first documented OR assessed by RECIST v1.1, in the absence of progression on bone scan assessed by PCWG3, which is subsequently confirmed. | Up to 3.5 years |
| Disease control (DC) | DC is defined as if a participant has achieved a best OR of confirmed CR or PR or SD as BOR assessed by RECIST v1.1, in the absence of progression on bone scan assessed by PCWG3. | Up to 3.5 years |
| Clinical benefit rate (CBR) | CBR is defined as the percentage of advanced cancer participants who achieve CR, PR, or at least 16 weeks/24 weeks of stable disease, assessed by RECIST v1.1, in the absence of progression on bone scan assessed by PCWG3, as a result of therapy. | Up to 3.5 years |
| Part A: Progression free survival (PFS) | PFS is defined as the time from the start of treatment until the date of objective disease progression or death (by any cause in the absence of progression), regardless of whether the participants withdraw from study treatment or receive another anti-cancer therapy prior to progression. | Up to 3.5 years |
| Percentage change from baseline in tumour size | The best percentage change from baseline in target lesion (TL) tumour size is the largest decrease (or smallest increase) from baseline for a participant, using RECIST v1.1 assessments. | Up to 3.5 years |
| Number of participants with cancer antigen 125 (CA125) response (for ovarian cancer participants) | CA125 response is defined as if at least a 50% reduction in CA125 levels from a pre-treatment sample. | From baseline up to 3.5 years |
| Radiological progression free survival (rPFS) (for prostate cancer participants) | PFS is defined as the time from the start of treatment until the date of objective disease progression or death (by any cause in the absence of progression), regardless of whether the participants withdraw from study treatment or receive another anti-cancer therapy prior to progression. | Up to 3.5 years |
| Change from baseline in prostate specific antigen 50 (PSA50) response rate (for prostate cancer participants) | PSA50 response is defined as if a ≥ 50% decrease in PSA from baseline to the lowest post-baseline PSA result, confirmed by a second consecutive PSA assessment at least 3 weeks later has been achieved. | From baseline up to 3.5 years |
| Change from baseline in PSA90 response rate (for prostate cancer participants) | PSA90 response is defined as if a ≥ 90% decrease in PSA from baseline to the lowest post-baseline PSA result, confirmed by a second consecutive PSA assessment at least 3 weeks later has been achieved. | From baseline up to 3.5 years |
| Change from baseline in PSA undetectable rate | Undetectable PSA is defined as a measurement of < 0.2 ng/mL. | At 3, 6 and 9 months |
| Time to PSA50/90 response (for prostate cancer participants) | Time to PSA50/90 response is defined as the time from the date of first dose of study intervention until the date of first documented PSA response (≥ 50%/90% decrease in PSA from baseline) that is confirmed by a second consecutive PSA assessment at least 3 weeks later. | Up to 3.5 years |
| Time to PSA progression (for prostate cancer participants) | Time to PSA progression is defined as the time from date of first dose of study intervention until the date of first documented PSA progression or the last PSA result in the absence of progression. | Up to 3.5 years |
| PSA PFS at 6 months (PSA-6) | PSA progression is defined as an increase in PSA of ≥ 25% from the nadir and an absolute increase of at least 2 ng/mL above nadir beyond 12 weeks. To assess the preliminary anti-tumour activity of AZD4956 monotherapy and in combination with anti-cancer. agent(s) | At 6 months |
| Area under the concentration-time curve (AUC) | To characterise the pharmacokinetics (PK) of AZD4956 when given orally as monotherapy and in combination with anti-cancer agent(s). | From date of first dose of study intervention up to 59 days after first dose |
| Maximum concentration (Cmax) | To characterise the pharmacokinetics (PK) of AZD4956 when given orally as monotherapy and in combination with anti-cancer agent(s). | From date of first dose of study intervention up to 59 days after first dose |
| Time to maximum concentration (Tmax) | To characterise the pharmacokinetics (PK) of AZD4956 when given orally as monotherapy and in combination with anti-cancer agent(s). | From date of first dose of study intervention up to 59 days after first dose |
| Individual and cumulative percentage of dose excreted unchanged in urine from time t1 to time t2 (fe(t1-t2)) | To characterise the pharmacokinetics (PK) of AZD4956 when given orally as monotherapy and in combination with anti-cancer agent(s). | From date of first dose of study intervention up to 16 days after first dose |
| Renal clearance (CLR) | To characterise the pharmacokinetics (PK) of AZD4956 when given orally as monotherapy and in combination with anti-cancer agent(s). | From date of first dose of study intervention up to 16 days after first dose |
| Individual and cumulative amount of unchanged drug excreted into urine from time t1 to time t2 (Ae(t1-t2)) | To characterise the pharmacokinetics (PK) of AZD4956 when given orally as monotherapy and in combination with anti-cancer agent(s). | From date of first dose of study intervention up to 16 days after first dose |
| Change in amount of KRAB-associated protein-1 phosphorylated on serine 824 [pKAP1 (Ser824)] biomarker in tumour cells at baseline and during treatment | To evaluate PD of AZD4956 in tumour cells when given orally as monotherapy and in combination with anti-cancer agent(s). | From Baseline up to 3.5 years |
| Not yet recruiting |
| Providence |
| Rhode Island |
| 02903 |
| United States |
| Research Site | Not yet recruiting | Houston | Texas | 77030 | United States |
| Research Site | Recruiting | Fairfax | Virginia | 22031 | United States |
| Research Site | Not yet recruiting | Melbourne | 3000 | Australia |
| Research Site | Not yet recruiting | Westmead | 2145 | Australia |
| Research Site | Not yet recruiting | Chūōku | 104-0045 | Japan |
| Research Site | Not yet recruiting | Kashiwa | 277-8577 | Japan |
| Research Site | Not yet recruiting | Seoul | 03080 | South Korea |
| Research Site | Not yet recruiting | Seoul | 120-752 | South Korea |
| Research Site | Not yet recruiting | Barcelona | 08023 | Spain |
| Research Site | Not yet recruiting | Barcelona | 08036 | Spain |
| Research Site | Not yet recruiting | Barcelona | 8035 | Spain |
| Research Site | Not yet recruiting | Logroño | 26006 | Spain |
| Research Site | Not yet recruiting | Pozuelo de Alarcón | 28223 | Spain |
| Research Site | Not yet recruiting | Seville | 41013 | Spain |
| Research Site | Not yet recruiting | Cambridge | CB2 0QQ | United Kingdom |
| Research Site | Not yet recruiting | London | SE1 9RT | United Kingdom |
| Research Site | Not yet recruiting | Sutton | SM25PT | United Kingdom |