Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as [14C]-AZD5305 (therapeutic dose), Saruparib
AZD5305 · 11 trials · 20 indications
Radiographic PFS (rPFS) is the primary endpoint of this study, defined as the time from randomization to radiographic progression, as assessed by the investigator per RECIST 1.1 (soft tissue) and/or PCWG3 criteria (bone), or death due to any cause.
MFS is defined as the time from randomisation until the date of first appearance of distant metastases, confirmed by standard clinical imaging \[computed tomography (CT)/ magnetic resonance imaging (MRI) and bone scan, or prostate-specific membrane antigen-positron emission tomography (PSMA-PET)\], as assessed by blinded independent central review (BICR) or death due to any cause.
PFS is defined as time from randomisation until progression per RECIST v1.1 as assessed by BICR, or death due to any cause.
Best objective response as assessed by the Investigator per RECIST 1.1
AUCinf
AUCinf
Cumulative amount excreted in urine, faeces and total (urine and faeces combined)
Amount excreted and cumulative amount excreted in urine, faeces and total (urine and faeces combined) expressed as a percentage of the administered dose.
AUClast
Cmax
tmax
t1/2(lambda)z
To evaluate the effects of saruparib on the PK of substrates of human drug transporters digoxin, furosemide, metformin hydrochloride, and rosuvastatin in participants with advanced solid malignancies.
To evaluate the effects of saruparib on the PK of substrates of human drug transporters digoxin, furosemide, metformin hydrochloride, and rosuvastatin in participants with advanced solid malignancies.
To evaluate the effects of saruparib on the PK of substrates of human drug transporters digoxin, furosemide, metformin hydrochloride, and rosuvastatin in participants with advanced solid malignancies.
To assess the relative bioavailability of saruparib tablets manufactured using a DC process versus RC process under fasted conditions.
To assess the relative bioavailability of saruparib tablets manufactured using a DC process versus RC process under fasted conditions.
To assess the relative bioavailability of saruparib tablets manufactured using a DC process versus RC process under fasted conditions.
To evaluate the effect of rabeprazole on saruparib PK profile following the administration of saruparib DC tablets.
To evaluate the effect of rabeprazole on saruparib PK profile following the administration of saruparib DC tablets.
To evaluate the effect of rabeprazole on saruparib PK profile following the administration of saruparib DC tablets.
To assess the effects of study treatment on γH2AX change in participants with localised prostate cancer
The effect of Itraconazole on the AUCinf of AZD5305 will be assessed. The ratios of geometric means of test intervention (AZD5305 + Itraconazole; parent and metabolite\[s\], if applicable) relative to reference intervention (AZD5305 alone) of AUCinf will be presented.
The effect of Itraconazole on the AUClast of AZD5305 will be assessed. The ratios of geometric means of test intervention (AZD5305 + Itraconazole; parent and metabolite\[s\], if applicable) relative to reference intervention (AZD5305 alone) of AUClast will be presented.
The effect of Itraconazole on the Cmax of AZD5305 will be assessed. The ratios of geometric means of test intervention (AZD5305 + Itraconazole; parent and metabolite\[s\], if applicable) relative to reference intervention (AZD5305 alone) of Cmax will be presented.
The effect of Itraconazole on the PK of AZD5305 will be assessed.
The effect of Itraconazole on the PK of AZD5305 will be assessed.
The effect of Itraconazole on the PK of AZD5305 will be assessed.
The effect of Itraconazole on the PK of AZD5305 will be assessed.
Number of patients with adverse events and with serious adverse events including abnormal clinical observations, abnormal ECG parameters, abnormal laboratory assessments and abnormal vital signs that changed from baseline will be assessed.
To assess the safety and tolerability of AZD5305 when given in combination with NHA.
Number of patients with adverse events and with serious adverse events including abnormal clinical observations, abnormal ECG parameters, abnormal laboratory assessments and abnormal vital signs that changed from baseline
A DLT is defined as any toxicity that occurs from the first dose of study treatment (either AZD5305 or combination anti-cancer agent) up to and including the planned end of Cycle 1 (the DLT assessment period) that is assessed as unrelated to the disease or disease-related processes under investigation. DLTs occurring outside the DLT window (ie, late onset toxicities) may be defined as a DLT after consultation with the sponsor and investigators, based on the emerging safety profile.
| Arm | Type | Description |
|---|---|---|
| Saruparib (AZD5305) + Physician's Choice ARPI - enzalutamide, darolutamide, or abiraterone | EXPERIMENTAL | Saruparib 60 mg + ARPI (enzalutamide, darolutamide, or abiraterone) : Participants will receive saruparib 60 mg orally once daily in combination with physician's choice of ARPI in cycles of 28 days |
| Placebo + Physician's Choice ARPI - enzalutamide, darolutamide, or abiraterone | PLACEBO_COMPARATOR | Placebo + ARPI (enzalutamide, darolutamide, or abiraterone): Participants will receive placebo orally once daily in combination with physician's choice of ARPI in cycles of 28 days |
| Cohort A: Saruparib (AZD5305) + Physician's Choice ADT | EXPERIMENTAL | Participants will receive saruparib along with ADT. |
| Cohort A: Placebo + Physician's Choice ADT | PLACEBO_COMPARATOR | Participants will receive matching placebo to saruparib along with ADT. |
| Cohort B: Saruparib (AZD5305) + Physician's Choice ADT + Abiraterone (and prednisone/prednisolone) | EXPERIMENTAL | Participants will receive saruparib, abiraterone and prednisolone/prednisone along with ADT. |
| Cohort B: Placebo + Physician's Choice ADT + Abiraterone (and prednisone/prednisolone) | PLACEBO_COMPARATOR | Participants will receive matching placebo to saruparib, abiraterone and prednisolone/prednisone along with ADT. |
| Arm 1: saruparib (AZD5305) plus camizestrant | EXPERIMENTAL | participants will receive saruparib (AZD5305) orally and camizestrant orally |
| Arm 2: Physician's choice CDK4/6i plus physician's choice ET | ACTIVE_COMPARATOR | agents are indicated below and should follow local guidelines: * Physician's Choice CDK4/6i: * abemaciclib orally, or * ribociclib orally, or * palbociclib orally. * Physician's Choice ET: * fulvestrant intramuscularly, or * One of the following AIs: * letrozole orally, or * anastrozole orally, or * exemestane orally |
| Arm 3: Physician's choice CDK4/6i plus camizestrant | EXPERIMENTAL | participants will receive camizestrant orally. Agents for CDK4/6i treatment are indicated above and should follow local guidelines |
| Arm 4: Saruparib (AZD5305) plus physician's choice ET | EXPERIMENTAL | participants will receive Saruparib (AZD5305) plus -Physician's Choice ET: * fulvestrant intramuscularly, or * One of the following AIs: * letrozole orally, or * anastrozole orally, or * exemestane orally |
| Arm 1: Saruparib (AZD5305) + Physician's Choice NHA | EXPERIMENTAL | Saruparib (AZD5305) + physician's choice NHA (Abiraterone, Darolutamide, or Enzalutamide) |
| Arm 2: Placebo + Physician's Choice NHA | PLACEBO_COMPARATOR | Placebo + physician's choice NHA (Abiraterone, Darolutamide, or Enzalutamide) |
| Saruparib (AZD5305) | EXPERIMENTAL | Saruparib |
| Primary Treatment Arm - AZD5305 | EXPERIMENTAL | Part A will assess absolute bioavailability via oral administration of Saruparib (AZD5305) and IV \[14C\]-saruparib microtracer. Part B will assess ADME via IV \[14C\]-saruparib administration |
| Treatment Cohort (Module 1) | ACTIVE_COMPARATOR | Period 1: participants will receive a single oral dose of cocktail substrate (digoxin, furosemide, metformin hydrochloride, and rosuvastatin) on Day 1. Period 2: participants will receive a single dose saruparib from Day 1 to 9, and a single dose of cocktail substrate on Day 5 in combination with saruparib. Period 3: participants will receive a single oral dose of saruparib daily. |
| Saruparib RC Cohort (Module 2) | ACTIVE_COMPARATOR | Period 1: participants will receive a single dose of RC saruparib. Period 2: participants will receive a single dose of DC saruparib. Period 3: participants will receive rabeprazole twice daily from Day 1 to 3, and a single dose of rabeprazole prior to DC saruparib on Day 4. Period 4: participants will receive RC saruparib daily for up to 3 cycles. |
| Saruparib DC Cohort (Module 2) | ACTIVE_COMPARATOR | Period 1: participants will receive a single dose of DC saruparib. Period 2: participants will receive a single dose of RC saruparib. Period 3: participants will receive rabeprazole twice daily from Day 1 to 3, and a single dose of rabeprazole prior to DC saruparib on Day 4. Period 4: participants will receive RC saruparib daily for up to 3 cycles. |
| Saruparib (AZD5305) only | OTHER | Participant will receive Saruparib (AZD5305) once daily for 21 days (+ up to 7 days) unless unacceptable toxicity or withdrawal of consent. Following the 21 days of study treatment, participants should undergo radical prostatectomy on Day 22 (+ up to 7 days) |
| Saruparib (AZD5305) + Darolutamide | OTHER | Participant will receive Saruparib (AZD5305) once daily + darolutamide twice daily for 21 days (+ up to 7 days) unless unacceptable toxicity or withdrawal of consent. Following the 21 days of study treatment, participants should undergo radical prostatectomy on Day 22 (+ up to 7 days). |
| No Treatment | OTHER | No study treatment is to be taken by the participants in this arm. Radical prostatectomy should be performed as per local practice |
| Darolutamide Only | OTHER | Participant will receive darolutamide twice daily for 21 days (+ up to 7 days) unless unacceptable toxicity or withdrawal of consent. Following the 21 days of study treatment, participants should undergo radical prostatectomy on Day 22 (+ up to 7 days). |
| Treatment Arm | EXPERIMENTAL | Part A: The participants will receive a single oral dose of AZD5305 on Day 1, followed by a 2-day washout. Then Itraconazole will be dosed for 3 days \[BD\] on Day 4 and \[OD\] on Days 5 and 6, then a single oral dose of AZD5305 administered concurrently with Itraconazole on Day 7 and only Itraconazole on Days 8 to 12. Part B: Patients proceeding to Part B after completing Part A of the study will receive AZD5305 OD as monotherapy. |
| Arm 1 (AZD5305 in combination with enzalutamide) | EXPERIMENTAL | Patients will receive an oral dose of AZD5305 and Enzalutamide once daily until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study treatment occur. |
| Arm 2 (AZD5305 in combination with abiraterone acetate) | EXPERIMENTAL | Patients will receive an oral dose of AZD5305 and Abiraterone Acetate once daily until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study treatment occur. |
| Arm 3 (AZD5305 in combination with darolutamide) | EXPERIMENTAL | Patients will receive an oral dose of AZD5305 once daily and Darolutamide twice daily until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study treatment occur. |
| Arm 4 (AZD5305 in combination with apalutamide) | EXPERIMENTAL | Patients will receive an oral dose of AZD5305 and Apalutamide once daily until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study treatment occur. |
| Module 1: AZD5305 Monotherapy | EXPERIMENTAL | AZD5305 Monotherapy |
| Module 2: AZD5305 + Paclitaxel | EXPERIMENTAL | AZD5305 + Paclitaxel |
| Module 3: AZD5305 + Carboplatin with or without Paclitaxel | EXPERIMENTAL | AZD5305 + Carboplatin with or without Paclitaxel |
| Module 4: AZD5305 + Trastuzumab Deruxtecan | EXPERIMENTAL | AZD5305 + T- DXd |
| Module 5 AZD5305 + Datopotamab Deruxtecan | EXPERIMENTAL | AZD5305 + Dato-DXd |
| Module 6 AZD5305 + Camizestrant | EXPERIMENTAL | AZD5305 + Camizestrant |
| Name | Type | Description |
|---|---|---|
| Saruparib | DRUG | Arm 1: Saruparib (AZD5305) + Physician's Choice ARPI (enzalutamide, darolutamide, or abiraterone) |
| Placebo | OTHER | Arm 2: Placebo + Physician's Choice ARPI (enzalutamide, darolutamide, or abiraterone) |
| Enzalutamide | DRUG | Arm 1: Saruparib (AZD5305) + Physician's Choice ARPI (enzalutamide, darolutamide, or abiraterone) Arm 2: Placebo + Physician's Choice ARPI |
| Darolutamide | DRUG | Arm 1: Saruparib (AZD5305) + Physician's Choice ARPI (enzalutamide, darolutamide, or abiraterone) Arm 2: Placebo + Physician's Choice ARPI |
| Abiraterone | DRUG | Arm 1: Saruparib (AZD5305) + Physician's Choice ARPI (enzalutamide, darolutamide, or abiraterone) Arm 2: Placebo + Physician's Choice ARPI |
| Abiraterone + Prednisolone/Prednisone | DRUG | Abiraterone will be administered orally in combination with prednisone/prednisolone. |
| Androgen Deprivation Therapy (ADT) | DRUG | Standard of care ADT will be administered. |
| Saruparib (AZD5305) | DRUG | Saruparib (AZD5305) is a potent and selective inhibitor of PARP1, with minimal effect on PARP2. |
| Camizestrant | DRUG | Camizestrant (AZD9833) is an orally bioavailable, next generation SERD with non-clinical and clinical activity in both ESR1 mutant and wild type settings . |
| Abemaciclib | DRUG | CDK4/6 Inhibitor |
| Ribociclib | DRUG | CDK4/6 Inhibitor |
| Palbociclib | DRUG | CDK 4/6 Inhibitor |
| Fulvestrant | DRUG | Endocrine Therapy |
| Letrozole | DRUG | Endorcine Therapy |
| Anastrozole | DRUG | Endocrine Therapy |
| Exemestane | DRUG | Endocrine Therapy |
| Abiraterone Acetate | DRUG | Oral |
| FoundationOne®CDx | DIAGNOSTIC_TEST | Tumors will be tested for positive HRDsig tumor by the investigational FoundationOne®CDx clinical trial assay. |
| [14C]-AZD5305 microtracer | DRUG | IV radiolabeled microtracer |
| [14C]-AZD5305 (therapeutic dose) | DRUG | IV radiolabeled PARP inhibitor |
| Digoxin | DRUG | Period 1: participants will receive a single oral dose of a cocktail of substrates (digoxin, furosemide, metformin hydrochloride, and rosuvastatin) on Day 1. Period 2: participants will receive a single oral dose of the cocktail of substrates in combination with saruparib on Day 5. |
| Furosemide | DRUG | Period 1: participants will receive a single oral dose of a cocktail of substrates (digoxin, furosemide, metformin hydrochloride, and rosuvastatin) on Day 1. Period 2: participants will receive a single oral dose of the cocktail of substrates in combination with saruparib on Day 5. |
| Metformin Hydrochloride | DRUG | Period 1: participants will receive a single oral dose of a cocktail of substrates (digoxin, furosemide, metformin hydrochloride, and rosuvastatin) on Day 1. Period 2: participants will receive a single oral dose of the cocktail of substrates in combination with saruparib on Day 5. |
| Rosuvastatin | DRUG | Period 1: participants will receive a single oral dose of a cocktail of substrates (digoxin, furosemide, metformin hydrochloride, and rosuvastatin) on Day 1. Period 2: participants will receive a single oral dose of the cocktail of substrates in combination with saruparib on Day 5. |
| Rabeprazole | DRUG | Period 3: Participants will receive two doses of rabeprazole per day from Day 1 to 3. On Day 4, participants will receive a dose of rabeprazole followed by DC saruparib. |
| No Treatment | OTHER | No study treatment is to be taken by the participants in this arm. Radical prostatectomy should be performed as per local practice |
| AZD5305 | DRUG | In Part A, the participants will receive a single dose of AZD5305 on Day 1 and Day 7. In Part B, the participants will receive AZD5305 once daily. |
| Itraconazole | DRUG | In Part A, the participants will receive Itraconazole twice daily on Day 4 and once daily on Days 5-12 |
| Apalutamide | DRUG | Patients will receive an oral dose of Apalutamide once daily |
| Paclitaxel | DRUG | IV Anti-microtubule agent |
| Carboplatin | DRUG | IV Platinum chemotherapeutic |
| T- Dxd | DRUG | IV Antibody-drug conjugate |
| Dato-DXd | DRUG | IV Antibody-drug conjugate |
Inclusion Criteria: * Participant must be ≥ 18 at the time of signing the informed consent. * Histologically documented diagnosis of prostate adenocarcinoma that is de novo or recurrent and hormone-sensitive. * Metastatic disease confirmed prior to initiation of previous treatment with docetaxel or...
AZD5305 is an investigational small molecule being studied for the treatment of advanced solid malignancies, ovarian cancer, and metastatic prostate cancer. It is being evaluated as a monotherapy and in combination with other anti-cancer agents in clinical trials.
AZD5305 is being developed by AstraZeneca PLC, which trades under the ticker AZN. The company is conducting clinical trials to evaluate the drug's safety and efficacy in patients with various types of cancer.
AZD5305 is in Phase 1 clinical development. It is an investigational drug and has not been approved by regulatory authorities. The ongoing trials are designed to assess its safety, tolerability, and preliminary efficacy in patients with advanced cancers.
AZD5305 is being studied in three Phase 1 trials. NCT04644068 evaluates it as monotherapy and in combination in advanced solid malignancies. NCT05367440 studies it with new hormonal agents in metastatic prostate cancer. NCT05573724 is a completed drug-drug interaction study with itraconazole.
Yes, AZD5305 is also known as [14C]-AZD5305 when administered at a therapeutic dose. The radiolabeled form is used in clinical studies to track the drug's absorption, distribution, metabolism, and excretion in the body.
The AZD5305 clinical development program includes a total of 702 participants across its trials. The largest study, NCT04644068, has an enrollment of 702 patients with advanced solid malignancies, while other trials have smaller cohorts.