Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Skin and Connective Tissue Diseases

Digestive System Diseases

Gland and Hormone Related Diseases

Rare Diseases

Prostatic Neoplasms

Breast Neoplasms

Pancreatic Neoplasms

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Glioma

Astrocytoma

Pancreatic Cancer

Ovarian Cancer

Ovarian Epithelial Cancer

Fallopian Tube Cancer

Antineoplastic Agents

All Drugs and Chemicals

Trastuzumab

Trastuzumab deruxtecan

Temozolomide

Poly(ADP-ribose) Polymerase Inhibitors

Antineoplastic Agents, Immunological

Antineoplastic Agents, Alkylating

Alkylating Agents

Immunoconjugates

Immunologic Factors

Participants with advanced/relapsed ovarian, breast, pancreatic, or prostate cancer who are deemed suitable for a PARPi will receive AZD9574 monotherapy at escalating cohorts.

Participants with breast cancer who are PARPi naive at doses determined in dose-escalation.

Participants with IDH 1/2-mutant glioma who are PARPi naive will receive AZD9574 and TMZ at escalating cohorts.

Participants with advanced/relapsed HER2-negative breast, ovarian, prostate, or pancreatic cancer and expressing BRCA1m, BRCA2m, PALB2m, RAD51Cm or RAD51Dm.

Participants with breast cancer (without BM).

Participants with advanced, unresectable, or metastatic solid tumours that are HER2-positive will receive a combination of AZD9574 and T-DXdat at escalating cohorts.

Participants with advanced, unresectable, or metastatic solid tumours in different types of cancers will receive a combination of AZD9574 and Dato-DXd at escalating cohorts.

Participants will receive AZD9574 orally.

AZD9574

Participants will receive temozolomide orally.

Participants will receive \[11C\]AZ1419 3391 intravenously.

[11C]AZ1419 3391

Participants will receive Dato-DXd intravenously.

Datopotamab Deruxtecan (Dato-DXd)

Participants will receive T-DXd intravenously.

Trastuzumab Deruxtecan (T-DXd)

AstraZeneca Clinical Study Information Center

This study will assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of AZD9574 individually and in combination with anti-cancer agents in 490 participants with advanced cancer that has recurred/progressed.

This is a modular phase I/IIa, multi-centre, multi-part, open-label, dose escalation, and dose expansion study.

Approximately 490 participants will be enrolled and assigned to study treatments.

This study consists of individual modules each evaluating safety and tolerability.

* Core protocol which contains information applicable to all modules.
* Module 1 (AZD9574 monotherapy):

This module will include 220 participants:

* Part A (dose-escalation cohorts) will include 130 participants (including backfills) with advanced/relapsed ovarian, breast, pancreatic or prostate cancer that are deemed suitable for a Poly ADP-Ribose Polymerase (PARPi) by the Investigator.
* Part B (dose-expansion cohorts):

This module will include up to 3 expansion cohorts with 30 participants in each:

* Cohort B1 will include participants with advanced/relapsed Human Epidermal Growth Factor Receptor 2 (HER2)-negative breast cancer participants with BRCA mutated (BRCA1m, and BRCA2m), PALB2 mutation (PALB2m), RAD51Cm or RAD51Dm, without evidence of brain metastasis at baseline Magnetic Resonance Imaging (MRI) scan.
* Cohort B2 will include participants with advanced/relapsed HER2-negative breast cancer participants with BRCA1m, BRCA2m, PALB2m, RAD51Cm or RAD51Dm, who have either untreated or treated brain metastases that are not requiring immediate local therapy.

  * Up to of 20 participants may be required to get 12 evaluable participants in each cohort for food effect and Acid Reducing Agent (ARA) investigations.

    • Module 2 (AZD9574 in combination with temozolomide (TMZ):
  * Part A (dose-escalation cohorts) will include 75 participants with Isocitrate Dehydrogenase (IDH)-mutant glioma.

    • Module 3 (PET Sub-study: AZD9574 monotherapy \[Panels 1 and 3), AZD9574 in combination with TMZ (Panel 2). This module will include 12 participants and is only applicable for Sweden.
  * Panel 1 (AZD9574 monotherapy) will include up to 8 participants with advanced/relapsed HER2-negative breast, ovarian, prostate, or pancreatic cancer and expressing BRCA1m, BRCA2m, PALB2m, RAD51Cm or RAD51Dm.
  * Panel 2 (AZD9574 + TMZ) will include up to 2 participants with IDH-mutant recurrent glioma.
  * Panel 3 (AZD9574 monotherapy) will include up to 2 participants with breast cancer (without BM).

    * Module 4 (AZD9574 in combination with Trastuzumab deruxtecan \[T-DXd\])

This module will include 90 participants (including backfills):

* Part A (dose escalation cohorts) will include participants with advanced, unresectable, or metastatic solid tumours that are HER2-positive.
* Part B (dose expansion cohorts) may be added in the future following a protocol amendment.

  * Module 5 (AZD9574 in combination with Datopotamab deruxtecan \[Dato-DXd\])

This module will include 90 participants (including backfills):

* Part A (dose escalation cohorts) will include participants with advanced, unresectable, or metastatic solid tumours in different types of cancers.
* Part B (dose expansion cohorts) may be added in the future amendment.

Study of AZD9574 as Monotherapy and in Combination With Anti-cancer Agents in Participants With Advanced Solid Malignancies

A Modular Phase I/IIa, Open-label, Multi-centre Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of Ascending Doses of AZD9574 as Monotherapy and in Combination With Anti-cancer Agents in Patients With Advanced Solid Malignancies (CERTIS1)

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. 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.

The safety and tolerability of AZD9574 as monotherapy and in combination with anti-cancer agents and TMZ in participants with advanced malignancies will be assessed.

The performance status of ECOG will be assessed based on an ECOG grade of 0 to 4 where '0' is a high grade while '4' is a low grade. An ECOG grade of '0' means that the participant is fully active, able to carry on all pre-disease performance without restriction. An ECOG grade of '4' means that the participant is completely disabled, cannot carry on any self-care, and is totally confined to a bed or chair.

The safety and tolerability of AZD9574 as monotherapy and in combination with anti-cancer agents in participants with advanced malignancies will be assessed at each dose level.

The AUC of AZD9574 following a single dose and at steady state after multiple dosing, when given orally as monotherapy and in combination with anti-cancer agents will be evaluated.

The Cmax of AZD9574 following a single dose and at steady state after multiple dosing, when given orally as monotherapy and in combination with anti-cancer agents will be evaluated.

The tmax of AZD9574 following a single dose and at steady state after multiple dosing, when given orally as monotherapy and in combination with anti-cancer agents will be evaluated.

The Cmin,ss of AZD9574 following a single dose and at steady state after multiple dosing, when given orally as monotherapy and in combination with anti-cancer agents will be evaluated.

The t1/2 of AZD9574 following a single dose and at steady state after multiple dosing, when given orally as monotherapy and in combination with anti-cancer agents will be evaluated.

The accumulation ratio of AZD9574 following a single dose and at steady state after multiple dosing, when given orally as monotherapy and in combination with anti-cancer agents will be evaluated.

The dose proportionality of AZD9574 following a single dose and at steady state after multiple dosing, when given orally as monotherapy and in combination with anti-cancer agents will be evaluated.

The PD biomarker modulations of pH2AX (Ser139) at baseline and during treatment or pre-treatment will be assessed in tumour tissue when given orally as monotherapy.

The percentage change in TL size will be determined for participants with measurable disease at baseline and is derived at each visit.

ORR is defined as the percentage of participants who have a confirmed response of Complete Response (CR) or Partial Response (PR) prior to any evidence of progression according to Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST v1.1) for solid tumours, RECIST v1.1 and/or Prostate Cancer Working Group 3 (PCWG3 \[bone\]) for prostate cancer, and Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) for brain metastases.

The DoR is defined as the time from the date of first documented response (which is subsequently confirmed) until date of documented progression or death in the absence of disease progression according to RECIST v1.1 for solid tumours, RECIST v1.1 and/or PCWG3 for prostate cancer, and RANO-BM for brain metastases.

TTR is defined as the time from first dose until the first documentation of a subsequently confirmed objective response according to RECIST v1.1 for solid tumours, RECIST v1.1 and/or PCWG3 for prostate cancer, and RANO-BM for brain metastases.

PFS and rPFS are defined as the time from start of first treatment until the date of objective disease progression or death regardless of whether the participant withdraws from study therapy or receives another anti-cancer therapy prior to progression according to RECIST v1.1 for solid tumours, RECIST v1.1 and/or PCWG3 for prostate cancer, and RANO-BM for brain metastases.

CA125 response is defined as at least a 50% reduction in CA125 levels from a pre-treatment sample.

PSA50 response is defined as the proportion of participants achieving a ≥ 50% decrease in Prostate Specific Antigen (PSA) from baseline to the lowest post-baseline PSA, confirmed by a consecutive PSA at least 3 weeks later and will be based on PSA evaluable participants.

In participants with prostate cancer, disease progression will be deemed to have occurred if soft tissue disease progression, bone lesion progression, or death are met.

The percentage change in TL size will be determined for participants with measurable disease at baseline and is derived at each visit by the measurability of TL according to Response Assessment in Neuro-Oncology - high-grade glioma (RANO-HGG) or Response Assessment in Neuro-Oncology - low-grade glioma (RANO-LGG).

The ORR is defined as the percentage of participant with high- or low-grade gliomas with at least one visit response of CR or PR according to RANO-HGG or RANO-LGG.

The DoR is defined as the time from the date of first documented response until the date of documented progression or death in the absence of disease progression according to RANO-HGG or RANO-LGG.

TTR is defined as the time from first dose until the first documentation of a subsequently confirmed objective response according to RANO-HGG or RANO-LGG.

The PFS is defined as the time from the start of study intervention until the date of objective disease progression or death regardless of whether the participant withdraws from study intervention or receives another anti-cancer therapy prior to progression according to RANO-HGG or RANO-LGG.

Occupancy (%) is defined as the estimated difference in radioligand binding to PARP1 from baseline to PET examination after drug administration.

The safety of radioligand \[11C\]AZ14193391 will be assessed.

To investigate the effect of a high-fat meal on the AUC of AZD9574 (Fasted and fed state).

To investigate the effect of a high-fat meal on the AUC (0-t) of AZD9574 (Fasted and fed state).

To investigate the effect of a high-fat meal on the Cmax of AZD9574 (Fasted and fed state).

To investigate the effect of a high-fat meal on the Tmax of AZD9574 (Fasted and fed state).

To investigate the effect of a high-fat meal on the Cmax ratio of AZD9574 (Fasted and fed state).

To assess the effect of famotidine on the AUC of AZD9574 (with and without famotidine).

To assess the effect of famotidine on the AUC (0-t) of AZD9574 (with and without famotidine).

To assess the effect of famotidine on the Cmax of AZD9574 (with and without famotidine).

To assess the effect of famotidine on the Tmax of AZD9574 (with and without famotidine).

To assess the effect of famotidine on the Cmax ratio of AZD9574 (with and without famotidine).

To characterise the AUC of AZD9574, T-DXd following a single dose and at steady state after multiple dosing, when given in combination with T-DXd.

To characterise the Cmax of AZD9574, T-DXd following a single dose and at steady state after multiple dosing, when given in combination with T-DXd.

To characterise the Tmax of AZD9574, T-DXd following a single dose and at steady state after multiple dosing, when given in combination with T-DXd.

To characterise the PD of AZD9574 in tumour tissue, following a single dose and at steady state after multiple dosing, when given orally in combination with T-DXd.

To investigate the immunogenicity of T-DXd.

To monitor risks associated with T-DXd (AESI) in study participants.

ORR is defined as the percentage of participants who have a confirmed response of Complete Response (CR) or Partial Response (PR) prior to any evidence of progression according to Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST v1.1).

The DoR is defined as the time from the date of first documented response (which is subsequently confirmed) until date of documented progression or death in the absence of disease progression according to RECIST v1.1.

PFS is defined as the time from start of first treatment until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the participant withdraws from study therapy or receives another anti-cancer therapy prior to progression according to RECIST v1.1.

TTR is defined as the time from first dose until the first documentation of a subsequently confirmed objective response according to RECIST v1.1.

To assess the AUC of AZD9574 and Dato-DXd.

To assess the Cmax of AZD9574 and Dato-DXd.

To assess the Tmax of AZD9574 and Dato-DXd.

To characterise the PD of AZD9574 in tumour tissue, following a single dose and at steady state after multiple dosing, when given orally in combination with Dato-DXd.

To investigate the immunogenicity of Dato-DXd.

ORR is defined as the percentage of participants who have a confirmed response of Complete Response (CR) or Partial Response (PR) prior to any evidence of progression according to Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST v1.1) and PCWG3 for prostate cancer.

PFS and rPFS are defined as the time from start of first treatment until the date of objective disease progression or death regardless of whether the participant withdraws from study therapy or receives another anti-cancer therapy prior to progression according to RECIST v1.1 for solid tumours, RECIST v1.1 and/or PCWG3 for prostate cancer.

To describe the prevalence (or incidence/frequency, etc) of Dato-DXd AESIs in study participants.

The AUC of AZD9574 following single dose and at steady state after multiple dosing, when given orally as monotherapy and in combination with TMZ will be evaluated.

The Cmax of AZD9574 following single dose and at steady state after multiple dosing, when given orally as monotherapy and in combination with TMZ will be evaluated.

The tmax of AZD9574 following single dose and at steady state after multiple dosing, when given orally as monotherapy and in combination with TMZ will be evaluated.

The Cmin,ss of AZD9574 following single dose and at steady state after multiple dosing, when given orally as monotherapy and in combination with TMZ will be evaluated.

The t1/2 of AZD9574 following single dose and at steady state after multiple dosing, when given orally as monotherapy and in combination with TMZ will be evaluated.

The accumulation ratio of AZD9574 following single dose and at steady state after multiple dosing, when given orally as monotherapy and in combination with TMZ will be evaluated.

ORR is defined as the percentage of participants who have a confirmed response of Complete Response (CR) or Partial Response (PR) prior to any evidence of progression according to Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST v1.1) for solid tumours, RECIST v1.1 and/or Prostate Cancer Working Group 3 (PCWG3 \[bone\]) for prostate cancer, and Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) for brain metastases and according to Response Assessment in Neuro-Oncology - high-grade glioma (RANO-HGG) or Response Assessment in Neuro-Oncology - low-grade glioma (RANO-LGG).

The DoR is defined as the time from the date of first documented response (which is subsequently confirmed) until date of documented progression or death in the absence of disease progression according to RECIST v1.1 for solid tumours, RECIST v1.1 and/or PCWG3 for prostate cancer, RANO-BM for brain metastases and RANO-HGG or RANO-LGG.

TTR is defined as the time from first dose until the first documentation of a subsequently confirmed objective response according to RECIST v1.1 for solid tumours, RECIST v1.1 and/or PCWG3 for prostate cancer, RANO-BM for brain metastases and RANO-HGG or RANO-LGG.

PFS and rPFS are defined as the time from start of first treatment until the date of objective disease progression or death regardless of whether the participant withdraws from study therapy or receives another anti-cancer therapy prior to progression according to RECIST v1.1 for solid tumours, RECIST v1.1 and/or PCWG3 for prostate cancer, RANO-BM for brain metastases and RANO-HGG or RANO-LGG.

Spots Global Cancer Trial Database for [11c]az1419 3391