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JOURNAL ONKOLOGIE – STUDIE
CERTIS1

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

Rekrutierend

NCT-Nummer:
NCT05417594

Studienbeginn:
August 2022

Letztes Update:
08.08.2024

Wirkstoff:
AZD9574, Temozolomide, [11C]AZ1419 3391, Datopotamab deruxtecan (Dato-DXd), Trastuzumab Deruxtecan (T-DXd)

Indikation (Clinical Trials):
Neoplasms

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
-

Sponsor:
AstraZeneca

Collaborator:
-

Kontakt

AstraZeneca Clinical Study Information Center
Kontakt:
Phone: 1-877-240-9479
E-Mail: information.center@astrazeneca.com» Kontaktdaten anzeigen
AstraZeneca Breast Cancer Study Locator Service
Kontakt:
Phone: 1-877-400-4656
E-Mail: az-bcsl@careboxhealth.com» Kontaktdaten anzeigen

Studienlocations
(3 von 31)

Research Site
69120 Heidelberg
(Baden-Württemberg)
GermanyZurückgezogen» Google-Maps
Research Site
55131 Mainz
(Rheinland-Pfalz)
GermanyZurückgezogen» Google-Maps
Research Site
G12 0YN Glasgow, Scotland
United KingdomRekrutierend» Google-Maps
Research Site
NE7 7DN Newcastle Upon Tyne
United KingdomRekrutierend» Google-Maps
Alle anzeigen

Studien-Informationen

Detailed Description:

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.

Ein-/Ausschlusskriterien

Inclusion Criteria:

- Eastern Cooperative Oncology Group performance status (ECOG PS) with no

deterioration over the previous 2 weeks.

- Progressive cancer at the time of study entry.

- Adequate organ and marrow function.

Module 1:

- Female participants of childbearing potential:

1. Must have a negative pregnancy test result at screening and prior to each cycle

of study treatment.

2. If sexually active with a non-sterilised male partner, must use at least one

highly effective method of birth control plus a barrier method from screening

to approximately 6 months after the last dose of study treatment.

- Female participants must not breastfeed and must not donate or retrieve ova for

their own use from screening to approximately 6 months after the last dose of study

treatment.

- Non-sterilised male participants who are sexually active with a female partner of

childbearing potential must use a condom with spermicide from screening to

approximately 3 months after the last dose of study intervention.

- Female partners of male participants should use at least one highly effective method

of contraception from screening to approximately 3 months after the last dose of

study intervention of the male participant.

- Male participants must refrain from fathering a child or donating sperm from the

start of study intervention and for approximately 3 months after the last dose of

study intervention.

Part A:

- Participants must have one of the following: (i) Histologically or cytologically

confirmed relapsed advanced ovarian, fallopian tube or primary peritoneal cancer and

evidence of a predicted loss of function germline or tumour mutation in one of the

following homologous recombination repair genes: BRCA1, BRCA2, PALB2, RAD51C or

RAD51D (ii) Histologically or cytologically confirmed HER2-negative carcinoma of the

breast with recurrent locally advanced or metastatic disease and evidence of a

predicted loss of function germline or tumour mutation in one of the following

homologous recombination repair genes: BRCA1, BRCA2, PALB2, RAD51C, or RAD51D.

(iii) Histologically or cytologically confirmed advanced/metastatic castration-resistant

prostate cancer (CRPC) and evidence of a predicted loss of function germline or tumour

mutation in one of the following homologous recombination repair genes:BRCA1, BRCA2,

PALB2, RAD51C, or RAD51D (d) Histologically or cytologically confirmed

advanced/metastatic pancreatic cancer and evidence of a predicted loss of function

germline or tumour mutation in one of the following homologous recombination repair

genes: BRCA1, BRCA2, PALB2, RAD51C, or RAD51D.

- Participants must have evaluable disease.

- Patients must be suitable for treatment with a PARPi.

- Participants must be capable of eating a high fat meal and adhering to fasting

restrictions.

Part B:

- Participants must have metastatic or recurrent locally advanced histologically or

cytologically confirmed Human Epidermal growth factor Receptor 2 (HER2)-negative

carcinoma of the breast and evidence of a predicted loss of function germline or

tumour mutation.

- Participants must have at least one lesion, not previously irradiated, that can be

accurately measured at baseline as ≥ 10 mm in the longest diameter.

- Participants who have received platinum chemotherapy for advanced breast cancer are

eligible to enter the study provided there has been no evidence of disease

progression during the platinum chemotherapy.

- Participants who have received prior platinum-based chemotherapy as

neo-adjuvant/adjuvant treatment are eligible provided at least 12 months have

elapsed between the last dose of platinum-based treatment and first dose of study

intervention.

Module 2:

- Participants must be suitable for treatment with TMZ.

- Participants must have IDH1/2-mutant glioma.

- Participants should have progressive disease after prior radiation therapy and one

prior line of alkylating chemotherapy for their disease.

- Recurrent disease must be evaluable by MRI.

- Female participants of childbearing potential must have a negative pregnancy test

result at screening and prior to each cycle administration of AZD9574 and TMZ.

- Adequate organ and marrow function.

Module 3:

All Panels:

- Female participants of childbearing potential:

1. Must have a negative pregnancy test result at screening and prior to each cycle

of study treatment.

2. If sexually active with a non-sterilised male partner, must use at least one

highly effective method of birth control plus a barrier method from screening

to approximately 6 months after the last dose of study treatment.

- Female participants must not breastfeed and must not donate or retrieve ova for

their own use from screening to approximately 6 months after the last dose of study

treatment.

Panel 1

- Participants must consent to provide mandated blood samples and archival/fresh

tumour tissue for confirmatory tests of their cancer using central laboratory.

- Participants must have one of the following:

1. Histologically or cytologically confirmed HER2-negative carcinoma of the breast

with recurrent locally advanced or metastatic disease and evidence of a

predicted loss of function germline or tumour mutation in BRCA1, BRCA2, PALB2,

RAD51C, or RAD51D,

2. Histologically or cytologically confirmed relapsed advanced ovarian, fallopian

tube or primary peritoneal cancer and evidence of a predicted loss of function

germline or tumour mutation in BRCA1, BRCA2, PALB2, RAD51C, or RAD51D

3. Histologically or cytologically confirmed advanced/metastatic

castration-resistant prostate cancer (CRPC) and evidence of a predicted loss of

function germline or tumour mutation in in BRCA1, BRCA2, PALB2, RAD51C or

RAD51D

4. Histologically or cytologically confirmed advanced/metastatic pancreatic cancer

and evidence of a predicted loss of function germline or tumour mutation in in

BRCA1, BRCA2, PALB2, RAD51C, or RAD51D.

- Participants must have evaluable disease: at least one measurable and/or

non-measurable lesions per RECIST 1.1

- Participants must be refractory to standard therapy or for which no standard therapy

exists.

- Any 2 participants in this panel must meet the following CNS criteria:

1. Participants must have previously treated and progressing or untreated brain

metastases confirmed by brain MRI at screening that do not need immediate local

therapy.

2. Participants should have stable neurological function for ≥ 14 days prior to

signing the main study ICF.

3. If receiving steroids, the dose should be stable or decreasing for ≥ 14 days

prior to signing the main study ICF.

Panel 2

- Participants must be suitable for treatment with TMZ.

- Participants must have IDH1/2-mutant glioma.

- Participants should have progressive disease after prior radiation therapy and one

prior line of alkylating chemotherapy for their disease.

- Recurrent disease must be evaluable by MRI and at least 1 tumour of > 1cm diameter

detected on MRI.

- Formalin-fixed, paraffin-embedded (FFPE) tumour sample from the primary cancer must

be available for central testing

- Adequate organ and marrow function (in the absence of transfusions or growth factor

support within 14 days prior to enrolment)

Panel 3

- Participants must consent to provide mandated blood samples and archival/fresh

tumour tissue for confirmatory tests of their cancer using central laboratory.

- Participants must have histologically or cytologically confirmed HER2-negative

carcinoma of the breast with recurrent locally advanced or metastatic disease and

evidence of a predicted loss of function germline or tumour mutation in in BRCA1,

BRCA2, PALB2, RAD51C or RAD51D .

- Participants must have evaluable disease: at least one measurable and/or

non-measurable lesions per RECIST 1.1 .

- Participants must be refractory to standard therapy or for which no standard therapy

exists.

Module 4:

- Participants must have the following HER2 status:

1. Participants with breast cancer must be IHC 3+ or IHC 2+/ISH-positive or IHC

2+/ISH-negative or IHC 1+ as determined by local testing using current American

Society of Clinical Oncology-College of American Pathologists (ASCO-CAP)

guidelines for scoring HER2 + breast cancer.

2. Participants with gastric cancer should be IHC 3+ or IHC 2+/ISH-positive based

on local tissue testing results.

3. Participants with non-breast and non-gastric cancers must have

HER2-overexpression (IHC 3+ or IHC 2+; as determined by local testing using

current ASCO-CAP guidelines for gastric IHC scoring).

4. Participants with NSCLC will also be eligible based on the presence of a

HER2activating mutation.

- Participants must have progressed following at least one prior systemic treatment

and not more than 2 prior lines of cytotoxic therapy for metastatic or advanced

disease and have no satisfactory alternative treatment option.

- Participants should have unresectable, or metastatic disease based on most recent

imaging. The following tumour types are eligible for this study: Breast cancer,

Non-Small Cell Lung Cancer, Colorectal Cancer,Bladder Cancer, Ovarian Cancer,

Gastric Cancer, and Other tumour types ( unresectable or metastatic biliary tract

cancer, cervical cancer, endometrial cancer, and pancreatic adenocarcinoma).

- Adequate organ and marrow function (in the absence of transfusions or growth factor

support) within 14 days prior to the first dose of study intervention.

- Left ventricular ejection fraction (LVEF) ≥ 50% by either echocardiogram (ECHO) or

multigated acquisition (MUGA) scan within 28 days before start of treatment.

- Participants must have at least one lesion not previously irradiated (or with

evidence of disease progression following radiation).

- Non-sterilised male participants who are sexually active with a female partner of

childbearing potential must use a condom with spermicide from screening to

approximately 6 months after the last dose of study intervention.

- Male participants must refrain from fathering a child or donating sperm during the

study and for approximately 6 months after the last dose of study intervention.

Module 5 :

- Participants should have unresectable, or metastatic disease based on most recent

imaging. The following tumour types are eligible for this study: TNBC, Endometrial

cancer, Ovarian Cancer and CRPC.

- Participants must have progressed following at least one prior systemic treatment

for metastatic or advanced disease and have no satisfactory alternative treatment

option.

- Participants must have at least one lesion, not previously irradiated that can be

accurately measured at baseline as ≥ 10 mm in the longest diameter.

- Non-sterilised male participants who are sexually active with a female partner of

childbearing potential must use a condom with spermicide from screening to at least

4 months after the last dose of study.

- Male participants must refrain from fathering a child or donating sperm during the

study and for at least 4 months after the last dose of study intervention.

- Adequate organ and marrow function (in the absence of transfusions or growth factor

support) within 14 days prior to the first dose of study intervention.

Module 4 & 5:

- Female participants of childbearing potential:

1. Must have a negative pregnancy test result at screening and prior to each cycle

of study intervention.

2. If sexually active with a non-sterilised male partner, must use at least one

highly effective method of birth control in combination with one effective

method (male condom plus spermicide) from screening until at least 7 months

after the last dose of study intervention

- Female participants must not breastfeed and must not donate or retrieve ova for any

use from screening to at least 7 months after the last dose of study intervention.

- Participants must provide an existing FFPE tumour sample for retrospective,

tissue-based IHC testing in a central laboratory to determine HER2 expression and

other correlatives.

- ECOG performance status of 0 or 1.

- Participants recruited specifically for PD evaluation must have at least 1 tumour

suitable for paired biopsies and be willing to consent to pre-treatment and

on-treatment biopsies.

Exclusion Criteria:

- Major surgery within 4 weeks of the first dose of study intervention.

- Radiotherapy with a wide field of radiation within 4 weeks or radiotherapy with a

limited field of radiation for palliation within 2 weeks of the first dose of study

intervention.

- With the exception of alopecia, any unresolved toxicities from prior therapy greater

than Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 at the time of

starting study intervention.

- Any known history of persisting severe pancytopenia due to any cause.

- Spinal cord compression unless asymptomatic, treated and stable and not requiring

continuous corticosteroids at a dose of > 10 mg prednisone/day or equivalent for at

least 4 weeks prior to start of study intervention.

- History of uncontrolled seizures or with need for concurrent administration of more

than 2 antiepileptic drugs, or history of epileptic disorder or any seizure history

unrelated to tumour.

- History of severe brain injury or stroke.

- Any evidence of severe or uncontrolled systemic diseases including active bleeding

diatheses, active infection including hepatitis B, hepatitis C and human

immunodeficiency virus (HIV).

- Uncontrolled intercurrent illness within the last 12 months.

- Any known predisposition to bleeding.

- Patients with myelodysplastic syndrome (MDS)/acute myeloid leukaemia (AML) or with

features suggestive of MDS/AML.

- Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to

swallow the formulated product or previous significant bowel resection that would

preclude adequate absorption of AZD9574.

- Known allergy or hypersensitivity to investigational product(s) or any of the

excipients of the investigational product(s).

- Known contra-indication to gadolinium-enhanced Magnetic Resonance Imaging (MRI) or,

if applicable, not able to be maintained on a stable or decreasing dose of

corticosteroid regimen (no increase for 7 days) prior to the baseline MRI.

- Any concurrent anti-cancer therapy or concurrent use of prohibited medications.

Module 1:

Part A:

- Participants that have received > one prior line of therapy in any setting with a

PARPi-based regimen.

- Participants with an INR >1.5 unless the patient is receiving non-vitamin K

antagonist oral anticoagulants.

- Participants with leptomeningeal disease (LMD) unless the LMD is of low volume or is

previously treated and the participant is asymptomatic or minimal symptoms.

- Participants with insulin-dependent diabetes.

- Participants currently on ARA treatment.

Part B:

- Participants with an International Normalised Ratio (INR) >1.5 unless the patient is

receiving non-vitamin K antagonist oral anticoagulants.

- Participants with LMD are excluded unless the LMD is of low volume or is previously

irradiated and the participant is asymptomatic from the LMD.

Module 2:

- Participants who have received a PARPi previously.

- Known hypersensitivity to TMZ or dacarbazine or known history of allergic reactions

attributed to compounds of similar chemical or biologic composition to AZD9574.

- Participants who have received > 1 prior line of alkylating chemotherapy regimen.

- Participants who had previously experienced Grade 4 haematological toxicities or

Grade 3 neutropenia associated with infections, or Grade 3 thrombocytopenia with

clinically significant bleeding during prior alkylating chemotherapy.

- Participants who have received bevacizumab within the last 6 months.

- Not requiring continuous corticosteroids at a dose of >10 mg prednisone/day or

equivalent for at least 4 weeks prior to start of study intervention.

Module 3:

All Panels

- Positive Allen's test

- Participants with a BMI > 30.0 kg/m2 or body weight > 100.0 kg

- Participants who suffer from claustrophobia.

- Participants with implanted metal devices or implants containing metal

- Participants with an INR >1.5

- Participants taking acid-reducing agents.

Panel 1

- Participants that have received > one prior line of therapy in any setting with a

PARPi-based regimen .

- Participants with leptomeningeal disease (LMD)

Panel 2

- Participants who have received a PARPi previously.

- Known hypersensitivity to TMZ.

- Participants who have received > 1 prior line of alkylating chemotherapy regimen.

- Participants who had previously experienced Grade 4 haematological toxicities or

Grade 3 neutropenia associated with infections, or Grade 3 thrombocytopenia with

clinically significant bleeding during prior alkylating chemotherapy.

- Participants who have received bevacizumab within the last 6 months.

Panel 3

- Participants that have received > one prior line of therapy in any setting with a

PARPi-based regimen.

- Participants with LMD

Module 4:

- Current or prior use of immunosuppressive medication within 14 days before the first

dose of T-DXd and within 4 weeks for continuous corticosteroids at a dose of

approximately > 10 mg prednisone/day or equivalent.

- Participants should not have received more than 2 prior lines of systemic cytotoxic

therapy.

- Prior treatment with HER2 directed TOPO1i ADCs and prior AZD9574 is not permitted.

- Participants must not enter the study if they received

chloroquine/hydroxychloroquine < 14 days prior to the first dose.

- Presence of unresolved toxicities from previous anti-cancer therapy, defined as

toxicities not yet resolved to Grade ≤ 1 or baseline.

- Participants with a known history of prior platelet transfusion(s) or febrile

neutropenia in the advanced disease treatment setting.

- Participants with medical history of myocardial infarction. Participants with

troponin levels above ULN at screening and without any myocardial related symptoms.

- History of (non-infectious) ILD/pneumonitis that required steroids, has current

ILD/pneumonitis, or suspected ILD/pneumonitis.

- Additional lung-related exclusion criteria: (a) Lung-specific intercurrent

clinically significant illnesses (b) Any autoimmune, connective tissue or

inflammatory disorders (c) Prior pneumonectomy.

- Pleural effusion, ascites or pericardial effusion that requires drainage, peritoneal

shunt, or Cell-free and Concentrated Ascites Reinfusion Therapy.

- Participants with a known hypersensitivity to T-DXd, any the excipients or other

mAbs.

- History of another primary malignancy.

- Participants with an uncontrolled infection requiring IV antibiotics, antivirals, or

antifungals.

- Active primary immunodeficiency, known uncontrolled active HIV infection or active

hepatitis B or hepatitis C infection.

Module 5:

- Current or prior use of immunosuppressive medication within 14 days before the first

dose of Dato-DXd and within 4 weeks for continuous corticosteroids at a dose of

approximately > 10 mg prednisone/day or equivalent.

- Corticosteroid mouthwash formulations are permitted to prevent and manage certain

AEs.

- Prior anti-cancer treatments:

(d) Participants should not have received more than 2 prior lines of systemic

cytotoxic therapy (e) Prior treatment with PARPi is permitted (f) Prior TOPO1

inhibitor therapy is NOT permitted (g) Prior treatment with TROP2-directed ADCs is

NOT permitted. (h) Prior radiation therapy requires the washout periods.

- Participants must not enter the study if they received chloroquine /

hydroxychloroquine < 14 days prior to the first dose.

- History of another primary malignancy.

- Participant has history of non-infectious ILD/pneumonitis including radiation

pneumonitis that required steroids, has current or suspected ILD/pneumonitis.

- Clinically severe pulmonary function compromise.

- Clinically significant corneal disease.

- History of severe hypersensitivity reactions to Dato-DXd, or any of the excipients

of the product.

- History of severe hypersensitivity reactions to other monoclonal antibodies.

- Participant is pregnant or breastfeeding or planning to become pregnant.

Studien-Rationale

Primary outcome:

1. Incidence of Adverse Events (AEs), and Serious Adverse Events (SAEs) (Time Frame - From first dose to post-treatment follow-up (approximately three years)):
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.

2. Changes from baseline in laboratory findings, electrocardiograms (ECGs), and vital signs (Time Frame - From last assessment prior to first dose to post-treatment follow up visit (approximately three years)):
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.

3. Change from baseline Eastern Cooperative Oncology Group performance status (ECOG PS) (Time Frame - From last assessment prior to first dose to post-treatment follow up visit (approximately three years)):
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.

4. Incidence of Dose Limiting Toxicities (DLTs) (Time Frame - Cycle 0 and Cycle 1 (Day 1 to Day 35)):
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.

Secondary outcome:

1. Area Under the Curve (AUC) (Time Frame - Cycle 0, Cycle 1 Day 1, Cycle 1 Day 16 (Cycle 0 = 7 days; Cycle 1 = 28 days)):
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.

2. Maximum plasma concentration (Cmax) (Time Frame - Cycle 0, Cycle 1 Day 1, Cycle 1 Day 16 (Cycle 0 = 7 days; Cycle 1 = 28 days)):
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.

3. Time to reach maximum plasma concentration (tmax) (Time Frame - Cycle 0, Cycle 1 Day 1, Cycle 1 Day 16 (Cycle 0 = 7 days; Cycle 1 = 28 days)):
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.

4. Minimum plasma concentration at steady state (Cmin,ss) (Time Frame - Cycle 0, Cycle 1 Day 1, Cycle 1 Day 16 (Cycle 0 = 7 days; Cycle 1 = 28 days)):
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.

5. Half-life (t1/2) (Time Frame - Cycle 0, Cycle 1 Day 1, Cycle 1 Day 16 (Cycle 0 = 7 days; Cycle 1 = 28 days)):
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.

6. Accumulation ratio (Time Frame - Cycle 0, Cycle 1 Day 1, Cycle 1 Day 16 (Cycle 0 = 7 days; Cycle 1 = 28 days)):
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.

7. Dose proportionality (Time Frame - Cycle 0, Cycle 1 Day 1, Cycle 1 Day 16 (Cycle 0 = 7 days; Cycle 1 = 28 days)):
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.

8. Module 1: Assessment of pH2AX (phospho-histone 2AX) (Ser139) PD biomarker modulations (Time Frame - Screening, Cycle 0 Day 1, Cycle 1 Day 8, and Cycle 1 day 15 (Cycle 0 = 7 days; Cycle 1 = 28 days)):
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.

9. Module 1: Percentage change in target lesion (TL) size (Time Frame - From Baseline to every 8 weeks until disease progression (approximately three years)):
The percentage change in TL size will be determined for participants with measurable disease at baseline and is derived at each visit.

10. Module 1: Objective Response Rate (ORR) (Time Frame - From Baseline to every 8 weeks until disease progression (approximately three years)):
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.

11. Module 1: Duration of Response (DoR) (Time Frame - First documented response until the date of documented progression or end of study (approximately three years)):
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.

12. Module 1: Time To Response (TTR) (Time Frame - From the first dose until the first documentation of a subsequently confirmed objective response (approximately three years)):
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.

13. Module 1: Progression Free Survival (PFS)/radiographic Progression-Free Survival (rPFS) (Time Frame - From the start of first treatment until the date of objective disease progression or death (approximately three years)):
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.

14. Module 1: Cancer Antigen 125 (CA125) response evaluated according to the GCIG criteria (for ovarian patients only) (Time Frame - From Screening until disease progression or death (approximately three years)):
CA125 response is defined as at least a 50% reduction in CA125 levels from a pre-treatment sample.

15. Module 1: Proportion of participants achieving a ≥ 50% decrease in PSA from baseline to the lowest post-baseline PSA result (for prostate cancer only) (Time Frame - From screening until disease progression or death (approximately three years)):
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.

16. Module 1: Radiological response evaluated according to RECIST v1.1 + Prostate Cancer Working Group 3 (PCWG3) response evaluation criteria (for prostate cancer only) (Time Frame - Up to the End Of Trial (EOT) [approximately three years]):
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.

17. Module 2: Percentage change in TL size (Time Frame - From Baseline to every 8 weeks until objective disease progression (approximately three years)):
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).

18. Module 2: ORR (Time Frame - From Baseline to every 8 weeks until objective disease progression (approximately three years)):
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.

19. Module 2: DoR (Time Frame - First documented response until the date of documented progression or end of study (approximately three years)):
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.

20. Module 2: TTR (Time Frame - First dose until the first documentation of a subsequently confirmed objective response (approximately three years)):
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.

21. Module 2: PFS (Time Frame - From the start of first treatment until the date of objective disease progression or death (approximately three years)):
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.

22. Module 3: Occupancy (Time Frame - From Screening to Cycle 2 Day 1):
Occupancy (%) is defined as the estimated difference in radioligand binding to PARP1 from baseline to PET examination after drug administration.

23. Module 3: Adverse Events (AEs) and Serious Adverse Events (SAEs) (Time Frame - From first dose to post-treatment follow-up (approximately three years)):
The safety of radioligand [11C]AZ14193391 will be assessed.

24. Module 1 (Food effect): AUC (Time Frame - Cycle 0 Day 1,2,3, Cycle 1 Day 1,2,8 to 15 and Cycle 2 Day 1, and Cycle 3 Day 1 (Cycle 0 = 7 days; Cycle 1 = 28 days)):
To investigate the effect of a high-fat meal on the AUC of AZD9574 (Fasted and fed state).

25. Module 1 (Food effect) : Area under the curve from 0 to t [AUC (0-t)] (Time Frame - Cycle 0 Day 1,2,3, Cycle 1 Day 1,2,8 to 15 and Cycle 2 Day 1, and Cycle 3 Day 1 (Cycle 0 = 7 days; Cycle 1 = 28 days)):
To investigate the effect of a high-fat meal on the AUC (0-t) of AZD9574 (Fasted and fed state).

26. Module 1 (Food effect): Cmax (Time Frame - Cycle 0 Day 1,2,3, Cycle 1 Day 1,2,8 to 15 and Cycle 2 Day 1, and Cycle 3 Day 1 (Cycle 0 = 7 days; Cycle 1 = 28 days)):
To investigate the effect of a high-fat meal on the Cmax of AZD9574 (Fasted and fed state).

27. Module 1 (Food effect): Tmax (Time Frame - Cycle 0 Day 1,2,3, Cycle 1 Day 1,2,8 to 15 and Cycle 2 Day 1, and Cycle 3 Day 1 (Cycle 0 = 7 days; Cycle 1 = 28 days)):
To investigate the effect of a high-fat meal on the Tmax of AZD9574 (Fasted and fed state).

28. Module 1 (Food effect) : Maximum plasma concentration (Cmax) ratio (with /without a high fat meal) (Time Frame - Cycle 0 Day 1,2,3, Cycle 1 Day 1,2,8 to 15 and Cycle 2 Day 1, and Cycle 3 Day 1 (Cycle 0 = 7 days; Cycle 1 = 28 days)):
To investigate the effect of a high-fat meal on the Cmax ratio of AZD9574 (Fasted and fed state).

29. Module 1 (ARA effect): AUC (Time Frame - Cycle 0 Day 1,3, Cycle 1 Day 1,2,8 to 15,16, Cycle 2 Day 1, Cycle 3 Day 1 (Cycle 0 = 7 days; Cycle 1 = 28 days)):
To assess the effect of famotidine on the AUC of AZD9574 (with and without famotidine).

30. Module 1 (ARA effect): AUC (0-t) (Time Frame - Cycle 0 Day 1,3, Cycle 1 Day 1,2,8 to 15,16, Cycle 2 Day 1, Cycle 3 Day 1 (Cycle 0 = 7 days; Cycle 1 = 28 days)):
To assess the effect of famotidine on the AUC (0-t) of AZD9574 (with and without famotidine).

31. Module 1 (ARA effect): Cmax (Time Frame - Cycle 0 Day 1,3, Cycle 1 Day 1,2,8 to 15,16, Cycle 2 Day 1, Cycle 3 Day 1 (Cycle 0 = 7 days; Cycle 1 = 28 days)):
To assess the effect of famotidine on the Cmax of AZD9574 (with and without famotidine).

32. Module 1 (ARA effect): Tmax (Time Frame - Cycle 0 Day 1,3, Cycle 1 Day 1,2,8 to 15,16, Cycle 2 Day 1, Cycle 3 Day 1 (Cycle 0 = 7 days; Cycle 1 = 28 days)):
To assess the effect of famotidine on the Tmax of AZD9574 (with and without famotidine).

33. Module 1 (ARA effect) : Cmax ratio (with /without famotidine) (Time Frame - Cycle 0 Day 1,3, Cycle 1 Day 1,2,8 to 15,16, Cycle 2 Day 1, Cycle 3 Day 1 (Cycle 0 = 7 days; Cycle 1 = 28 days)):
To assess the effect of famotidine on the Cmax ratio of AZD9574 (with and without famotidine).

34. Module 4 : AUC (Time Frame - AZD9574: Cycle 1 Day X1 (first AZD9574 dosing), 15, X2 (last of AZD9574 dosing), Cycle 2 Day 1, X1 (first AZD9574 dosing), X2 (last of AZD9574 dosing),15 and Cycle 3 Day 1 T-DXd: Cycle 1 Day X1 (pre-dose AZD9574), 1, 15, Cycle 2 Day 1, and Cycle 4 Day 1):
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.

35. Module 4 : Cmax (Time Frame - AZD9574: Cycle 1 Day X1 (first AZD9574 dosing), 15, X2 (last of AZD9574 dosing), Cycle 2 Day 1, X1 (first AZD9574 dosing), X2 (last of AZD9574 dosing),15 and Cycle 3 Day 1 T-DXd: Cycle 1 Day X1 (pre-dose AZD9574), 1, 15, Cycle 2 Day 1, and Cycle 4 Day 1):
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.

36. Module 4 : Tmax (Time Frame - AZD9574: Cycle 1 Day X1 (first AZD9574 dosing), 15, X2 (last of AZD9574 dosing), Cycle 2 Day 1, X1 (first AZD9574 dosing), X2 (last of AZD9574 dosing),15 and Cycle 3 Day 1 T-DXd: Cycle 1 Day X1 (pre-dose AZD9574), 1, 15, Cycle 2 Day 1, and Cycle 4 Day 1):
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.

37. Module 4 : Assessment of pH2AX (phospho-histone 2AX) (Ser139) PD biomarker modulations (Time Frame - Screening, Cycle 1 Day X2 [last of AZD9574 dosing] (Cycle 1 = 28 days)):
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.

38. Module 4 : Presence of ADAs for T-DXd (Time Frame - Cycle 1 Day 1, Cycle 2 Day 1, Cycle 3 Day 1, EoT(End of treatment) ± 7 days, Safety follow up (FU) 40 [+ 7] days after last dose):
To investigate the immunogenicity of T-DXd.

39. Module 4 : Incidence of Adverse event of special interest (AESI) (Time Frame - From first dose until the safety FU (40 [+ 7] days) after discontinuation):
To monitor risks associated with T-DXd (AESI) in study participants.

40. Module 4: ORR (Time Frame - From Baseline to every 6 weeks until disease progression (approximately three years)):
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).

41. Module 4: DoR (Time Frame - First documented response until the date of documented progression or end of study (approximately three years)):
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.

42. Module 4: PFS (Time Frame - From the start of first treatment until the date of objective disease progression or death (approximately three years)):
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.

43. Module 4: TTR (Time Frame - From the first dose until the first documentation of a subsequently confirmed objective response (approximately three years)):
TTR is defined as the time from first dose until the first documentation of a subsequently confirmed objective response according to RECIST v1.1.

44. Module 5 : AUC (Time Frame - AZD9574: Cycle 1 Day X1 (first AZD9574 dosing), 15, X2 (last of AZD9574 dosing), Cycle 2 Day 1, X1 (first AZD9574 dosing), 15, Cycle 3 Day 1 Dato-DXd: Cycle 1 Day 1, X1 (pre-dose AZD9574), 15, X2 (pre-dose AZD9574), Cycle 2 Day 1, Cycle 3 Day 1):
To assess the AUC of AZD9574 and Dato-DXd.

45. Module 5 : Cmax (Time Frame - AZD9574: Cycle 1 Day X1 (first AZD9574 dosing), 15, X2 (last of AZD9574 dosing), Cycle 2 Day 1, X1 (first AZD9574 dosing), 15, Cycle 3 Day 1 Dato-DXd: Cycle 1 Day 1, X1 (pre-dose AZD9574), 15, X2 (pre-dose AZD9574), Cycle 2 Day 1, Cycle 3 Day 1):
To assess the Cmax of AZD9574 and Dato-DXd.

46. Module 5 : Tmax (Time Frame - AZD9574: Cycle 1 Day X1 (first AZD9574 dosing), 15, X2 (last of AZD9574 dosing), Cycle 2 Day 1, X1 (first AZD9574 dosing), 15, Cycle 3 Day 1 Dato-DXd: Cycle 1 Day 1, X1 (pre-dose AZD9574), 15, X2 (pre-dose AZD9574), Cycle 2 Day 1, Cycle 3 Day 1):
To assess the Tmax of AZD9574 and Dato-DXd.

47. Module 5 : Assessment of pH2AX (phospho-histone 2AX) (Ser139) PD biomarker modulations (Time Frame - Screening, Cycle 1 Day X2 [last of AZD9574 dosing] (Cycle 1 = 28 days)):
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.

48. Module 5 : Presence of positive ADAs for Dato-DXd (Time Frame - Cycle 1 Day 1, Cycle 2 Day 1, Cycle 3 Day 1, EoT(End of treatment) ± 7 days, Safety follow up (FU) 28 [+ 7] days after last dose):
To investigate the immunogenicity of Dato-DXd.

49. Module 5: ORR (Time Frame - From Baseline to every 6 weeks until disease progression (approximately three years)):
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.

50. Module 5: DoR (Time Frame - First documented response until the date of documented progression or end of study (approximately three years)):
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.

51. Module 5: TTR (Time Frame - From the first dose until the first documentation of a subsequently confirmed objective response (approximately three years)):
TTR is defined as the time from first dose until the first documentation of a subsequently confirmed objective response according to RECIST v1.1.

52. Module 5: Progression Free Survival (PFS)/radiographic Progression-Free Survival (rPFS) (Time Frame - From the start of first treatment until the date of objective disease progression or death (approximately three years)):
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.

53. Module 5 : Incidence of AESIs (Time Frame - From first dose until the safety FU (40 [+ 7] days) after discontinuation):
To describe the prevalence (or incidence/frequency, etc) of Dato-DXd AESIs in study participants.

54. Module 3: AUC (Time Frame - Cycle 0 Day 1 & 5, Cycle 1 Day 5 (Cycle 0 = 7 days; Cycle 1 = 28 days)):
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.

55. Module 3: Cmax (Time Frame - Cycle 0 Day 1 & 5, Cycle 1 Day 5 (Cycle 0 = 7 days; Cycle 1 = 28 days)):
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.

56. Module 3: tmax (Time Frame - Cycle 0 Day 1 & 5, Cycle 1 Day 5 (Cycle 0 = 7 days; Cycle 1 = 28 days)):
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.

57. Module 3: Cmin,ss (Time Frame - Cycle 0 Day 1 & 5, Cycle 1 Day 5 (Cycle 0 = 7 days; Cycle 1 = 28 days)):
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.

58. Module 3: t1/2 (Time Frame - Cycle 0 Day 1 & 5, Cycle 1 Day 5 (Cycle 0 = 7 days; Cycle 1 = 28 days)):
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.

59. Module 3: Accumulation ratio (Time Frame - Cycle 0 Day 1 & 5, Cycle 1 Day 5 (Cycle 0 = 7 days; Cycle 1 = 28 days)):
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.

60. Module 3: Percentage change in target lesion (TL) size (Time Frame - From Baseline to every 8 weeks until disease progression (approximately three years)):
The percentage change in TL size will be determined for participants with measurable disease at baseline and is derived at each visit.

61. Module 3: ORR (Time Frame - From Baseline to every 8 weeks until disease progression (approximately three years)):
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).

62. Module 3: DoR (Time Frame - First documented response until the date of documented progression or end of study (approximately three years)):
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.

63. Module 3: TTR (Time Frame - From the first dose until the first documentation of a subsequently confirmed objective response (approximately three years)):
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.

64. Module 3: Progression Free Survival (PFS)/radiographic Progression-Free Survival (rPFS) (Time Frame - From the start of first treatment until the date of objective disease progression or death (approximately three years)):
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.

65. Module 3: Cancer Antigen 125 (CA125) response evaluated according to the GCIG criteria (for ovarian patients only) (Time Frame - From Screening until disease progression or death (approximately three years)):
CA125 response is defined as at least a 50% reduction in CA125 levels from a pre-treatment sample.

66. Module 3: Proportion of participants achieving a ≥ 50% decrease in PSA from baseline to the lowest post-baseline PSA result (for prostate cancer only) (Time Frame - From screening until disease progression or death (approximately three years)):
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.

67. Module 3: Radiological response evaluated according to RECIST v1.1 + Prostate Cancer Working Group 3 (PCWG3) response evaluation criteria (for prostate cancer only) (Time Frame - Up to the End Of Trial (EOT) [approximately three years]):
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.

68. Module 4: Cancer Antigen 125 (CA125) response evaluated according to the GCIG criteria (for ovarian patients only) (Time Frame - From Screening until disease progression or death (approximately three years)):
CA125 response is defined as at least a 50% reduction in CA125 levels from a pre-treatment sample.

69. Module 5: Cancer Antigen 125 (CA125) response evaluated according to the GCIG criteria (for ovarian patients only) (Time Frame - From Screening until disease progression or death (approximately three years)):
CA125 response is defined as at least a 50% reduction in CA125 levels from a pre-treatment sample.

70. Module 5: Proportion of participants achieving a ≥ 50% decrease in PSA from baseline to the post-baseline PSA result (for prostate cancer only) (Time Frame - From screening until disease progression or death (approximately three years)):
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.

Studien-Arme

  • Experimental: Module 1 Part A: Dose escalation
    Participants with advanced/relapsed ovarian, breast, pancreatic, or prostate cancer who are deemed suitable for a PARPi will receive AZD9574 monotherapy at escalating cohorts.
  • Experimental: Module 1 Part B: Dose expansion
    Participants with breast cancer who are PARPi naive at doses determined in dose-escalation.
  • Experimental: Module 2 Part A: Dose escalation
    Participants with IDH 1/2-mutant glioma who are PARPi naive will receive AZD9574 and TMZ at escalating cohorts.
  • Experimental: Module 3 Panel 1: AZD9574 monotherapy (Sweden only)
    Participants with advanced/relapsed HER2-negative breast, ovarian, prostate, or pancreatic cancer and expressing BRCA1m, BRCA2m, PALB2m, RAD51Cm or RAD51Dm.
  • Experimental: Module 3 Panel 2: AZD9574 + TMZ (Sweden only)
    Participants with IDH 1/2-mutant glioma who are PARPi naive will receive AZD9574 and TMZ at escalating cohorts.
  • Experimental: Module 3 Panel 3: AZD9574 monotherapy (Sweden only)
    Participants with breast cancer (without BM).
  • Experimental: Module 4 Part A: Dose escalation (AZD9574 + T-DXdat)
    Participants with advanced, unresectable, or metastatic solid tumours that are HER2-positive will receive a combination of AZD9574 and T-DXdat at escalating cohorts.
  • Experimental: Module 5 Part A : Dose escalation (AZD9574 + Dato-DXd)
    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.

Geprüfte Regime

  • AZD9574:
    Participants will receive AZD9574 orally.
  • Temozolomide:
    Participants will receive temozolomide orally.
  • [11C]AZ1419 3391:
    Participants will receive [11C]AZ1419 3391 intravenously.
  • Datopotamab Deruxtecan (Dato-DXd):
    Participants will receive Dato-DXd intravenously.
  • Trastuzumab Deruxtecan (T-DXd):
    Participants will receive T-DXd intravenously.

Quelle: ClinicalTrials.gov


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