Study of AZD5305 as Monotherapy and in Combination With Anti-cancer Agents in Patients With Advanced Solid Malignancies

NCT ID: NCT04644068

Last Updated: 2025-08-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

702 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-11-12

Study Completion Date

2027-06-01

Brief Summary

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This research is designed to determine if experimental treatment with PARP inhibitor, AZD5305, alone, or in combination with anti-cancer agents is safe, tolerable, and has anti-cancer activity in patients with advanced solid tumors.

Detailed Description

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This study is a Phase I/IIa modular, open-label, multi-center study of AZD5305 administered orally, either as monotherapy or in combination with other anti-cancer agents in patients with advanced solid malignancies.

Conditions

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Ovarian Cancer Breast Cancer Pancreatic Cancer Prostate Cancer Additional Indications Below for Module 4 and 5 Non-small Cell Lung Cancer Colorectal Cancer Bladder Cancer Gastric Cancer Biliary Cancer Cervical Cancer Endometrial Cancer Small Cell Lung Cancer Only in Module 5

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

The study consists of individual modules each evaluating the safety and tolerability of AZD5305 dosed as monotherapy, or with a specific combination partner:

* Module 1 (AZD5305 monotherapy)
* Module 2 (AZD5305 in combination with paclitaxel)
* Module 3 (AZD5305 in combination with carboplatin, with or without paclitaxel)
* Module 4 (AZD5305 in combination with T DXd)
* Module 5 (AZD5305 in combination with Dato-DXd).
* Module 6 (AZD5305 in combination with Camizestrant)

Modules 1 and 4 has 2 study parts: Part A consisting of dose-escalation cohorts and Part B, consisting of expansion cohorts. Modules 2, 3, 5 and 6 have only PART A.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Module 1: AZD5305 Monotherapy

AZD5305 Monotherapy

Group Type EXPERIMENTAL

AZD5305

Intervention Type DRUG

Oral PARP inhibitor

Module 2: AZD5305 + Paclitaxel

AZD5305 + Paclitaxel

Group Type EXPERIMENTAL

AZD5305

Intervention Type DRUG

Oral PARP inhibitor

Paclitaxel

Intervention Type DRUG

IV Anti-microtubule agent

Module 3: AZD5305 + Carboplatin with or without Paclitaxel

AZD5305 + Carboplatin with or without Paclitaxel

Group Type EXPERIMENTAL

AZD5305

Intervention Type DRUG

Oral PARP inhibitor

Paclitaxel

Intervention Type DRUG

IV Anti-microtubule agent

Carboplatin

Intervention Type DRUG

IV Platinum chemotherapeutic

Module 4: AZD5305 + Trastuzumab Deruxtecan

AZD5305 + T- DXd

Group Type EXPERIMENTAL

AZD5305

Intervention Type DRUG

Oral PARP inhibitor

T- Dxd

Intervention Type DRUG

IV Antibody-drug conjugate

Module 5 AZD5305 + Datopotamab Deruxtecan

AZD5305 + Dato-DXd

Group Type EXPERIMENTAL

AZD5305

Intervention Type DRUG

Oral PARP inhibitor

Dato-DXd

Intervention Type DRUG

IV Antibody-drug conjugate

Module 6 AZD5305 + Camizestrant

AZD5305 + Camizestrant

Group Type EXPERIMENTAL

AZD5305

Intervention Type DRUG

Oral PARP inhibitor

Camizestrant

Intervention Type DRUG

Oral SERD Molecule

Interventions

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AZD5305

Oral PARP inhibitor

Intervention Type DRUG

Paclitaxel

IV Anti-microtubule agent

Intervention Type DRUG

Carboplatin

IV Platinum chemotherapeutic

Intervention Type DRUG

T- Dxd

IV Antibody-drug conjugate

Intervention Type DRUG

Dato-DXd

IV Antibody-drug conjugate

Intervention Type DRUG

Camizestrant

Oral SERD Molecule

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Age ≥ 18 at the time of screening
* Histological or cytological confirmation of advanced malignancy considered to be suitable for study treatment and meeting module specific eligibility criteria..
* Eastern Cooperative Oncology Group Performance status (ECOG PS: 0-2)
* Life expectancy ≥ 12 weeks
* Progressive cancer at the time of study entry
* Patients must have evaluable disease as defined in module-specific criteria for Part A and Part B
* Adequate organ and marrow function as defined by the protocol.
* For Part B expansion cohorts: Provision of formalin-fixed and paraffin embedded (FFPE) tumour specimen is mandatory, where available, except if stated that it is optional in a specific Module.

For Part A:

\- Patients may have received up to one prior line of therapy with a PARPi-based regimen (either as a treatment or as maintenance)

For Part B:

\- Patients must not have received prior therapy with a PARPi-based regimen (either as a treatment or as maintenance).

Exclusion Criteria

* Treatment with any of the following:

1. Nitrosourea or mitomycin C within 6 weeks of the first dose of study treatment
2. Any investigational agents or study drugs from a previous clinical study within 5 half-lives or 3 weeks (whichever is shorter) of the first dose of study treatment
3. Any other chemotherapy, immunotherapy or anticancer agents within 3 weeks of the first dose of study treatment
4. Any live virus or bacterial vaccine within 28 days of the first dose of study treatment
* Concomitant use of medications or herbal supplements known to be cytochrome P450 3A4 (CYP3A4) strong inhibitors or inducers.
* Concomitant use of drugs that are known to prolong or shorten QT and have a known risk of Torsades de Pointes.
* Receiving continuous corticosteroids at a dose of \>10 mg prednisone/day or equivalent for any reason.
* Major surgery within 4 weeks of the first dose of study treatment.
* 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 treatment.
* Any history of persisting (\> 2 weeks) severe pancytopenia due to any cause
* Spinal cord compression or brain metastases unless asymptomatic, treated and stable and not requiring continuous corticosteroids at a dose of \>10mg prednisone/day or equivalent for at least 4 weeks prior to start of study treatment. Patients with leptomeningeal carcinomatosis are excluded.
* patient with known predisposition to bleeding (e.g., active peptic ulceration, recent \[within 6 months\] haemorrhagic stroke, proliferative diabetic retinopathy).
* Cardiac conditions as defined by the clinical study protocol
* Other cardiovascular diseases as defined by any of the following:

1. Symptomatic heart failure,
2. uncontrolled hypertension,
3. hypertensive heart disease with significant left ventricular hypertrophy
4. acute coronary syndrome (ACS)/acute myocardial infarction (AMI), unstable angina pectoris, coronary intervention procedure with percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) within 6 months.
5. cardiomyopathy of any etiology
6. presence of clinically significant valvular heart disease
7. history of atrial or ventricular arrhythmia requiring treatment; subjects with atrial fibrillation and optimally controlled ventricular rate (\< 100 beats per minute) are permitted.
8. subjects with atrial fibrillation and optimally controlled ventricular rate are permitted
9. transient ischaemic attack, or stroke within 6 months prior to screening
10. patients with symptomatic hypotension at screening
* Patients with myelodysplastic syndrome/acute myeloid leukaemia or with features suggestive of myelodysplastic syndrome (MDS)/acute myeloid leukaemia (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 AZD5305
* Known allergy or hypersensitivity to investigational product(s) or any of the excipients of the investigational product(s).

Prior malignancy whose natural history, in the Investigator's opinion, has the potential to interfere with safety and efficacy assessments of the investigational regimen.

other module-specific criteria may apply
Minimum Eligible Age

18 Years

Maximum Eligible Age

130 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AstraZeneca

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Timothy Yap

Role: PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Locations

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Boston, Massachusetts, United States

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Boston, Massachusetts, United States

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New York, New York, United States

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Oklahoma City, Oklahoma, United States

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Houston, Texas, United States

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Heidelberg, , Australia

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Melbourne, , Australia

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Vancouver, British Columbia, Canada

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Toronto, Ontario, Canada

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Montreal, Quebec, Canada

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Montreal, Quebec, Canada

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Beijing, , China

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Changchun, , China

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Changsha, , China

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Chengdu, , China

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Chongqing, , China

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Guangzhou, , China

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Harbin, , China

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Jining, , China

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Shandong, , China

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Shanghai, , China

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Shanghai, , China

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Taiyuan, , China

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Wuhan, , China

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Xi'an, , China

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Brno, , Czechia

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Prague, , Czechia

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Budapest, , Hungary

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Budapest, , Hungary

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Budapest, , Hungary

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Milan, , Italy

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Milan, , Italy

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Modena, , Italy

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Napoli, , Italy

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Padua, , Italy

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Roma, , Italy

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Chūōku, , Japan

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Kōtoku, , Japan

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Bydgoszcz, , Poland

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Gdansk, , Poland

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Gdynia, , Poland

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Grzepnica, , Poland

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Lodz, , Poland

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Torun, , Poland

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Warsaw, , Poland

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Moscow, , Russia

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Moscow, , Russia

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Moscow, , Russia

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Moscow, , Russia

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Barcelona, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Málaga, , Spain

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Pozuelo de Alarcón, , Spain

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Seville, , Spain

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Chernivtsі, , Ukraine

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Ivano-Frankivsk, , Ukraine

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Kyiv, , Ukraine

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Uzhhorod, , Ukraine

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Cambridge, , United Kingdom

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Manchester, , United Kingdom

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Oxford, , United Kingdom

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Sutton, , United Kingdom

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Countries

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United States Australia Canada China Czechia Hungary Italy Japan Poland Russia South Korea Spain Ukraine United Kingdom

References

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Illuzzi G, Staniszewska AD, Gill SJ, Pike A, McWilliams L, Critchlow SE, Cronin A, Fawell S, Hawthorne G, Jamal K, Johannes J, Leonard E, Macdonald R, Maglennon G, Nikkila J, O'Connor MJ, Smith A, Southgate H, Wilson J, Yates J, Cosulich S, Leo E. Preclinical Characterization of AZD5305, A Next-Generation, Highly Selective PARP1 Inhibitor and Trapper. Clin Cancer Res. 2022 Nov 1;28(21):4724-4736. doi: 10.1158/1078-0432.CCR-22-0301.

Reference Type DERIVED
PMID: 35929986 (View on PubMed)

Related Links

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https://www.breastcancerstudylocator.com/trial/listing/260668

Breast Cancer Study Locator details (for US)

Other Identifiers

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2020-002688-77

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

D9720C00001

Identifier Type: -

Identifier Source: org_study_id

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