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

A Modular Phase I/IIa, Open-label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of Ascending Doses of AZD5305 as Monotherapy and in Combination With Anti-cancer Agents in Patients With Advanced Solid Malignancies

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Cervical Cancer; Breast Cancer; Gastric Cancer; Colorectal Cancer; Pancreatic Cancer; Ovarian Cancer; Prostate Cancer; Bladder Cancer; Endometrial Cancer; Non-small Cell Lung Cancer; Biliary Cancer; Additional Indications Below for Module 4 and 5; Small Cell Lung Cancer Only in Module 5
• Intervention / Treatment: Drug: AZD5305; Drug: Paclitaxel; Drug: Carboplatin; Drug: T- Dxd; Drug: Dato-DXd; Drug: Camizestrant

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 702
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • Heidelberg, Australia, 3084
    • Research Site
  • Melbourne, Australia, 3000
    • Research Site
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1K1
      • Research Site
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Research Site
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Research Site
    • Montreal, Quebec, Canada, H2X 0A9
      • Research Site
• China
  • Beijing, China, 100142
    • Research Site
  • Changchun, China, 130021
    • Research Site
  • Changsha, China, 410013
    • Research Site
  • Chengdu, China, 610041
    • Research Site
  • Chongqing, China, 400030
    • Research Site
  • Guangzhou, China, 510060
    • Research Site
  • Harbin, China, 150081
    • Research Site
  • Jining, China, 272029
    • Research Site
  • Shandong, China
    • Research Site
  • Shanghai, China, 200032
    • Research Site
  • Shanghai, China, 200025
    • Research Site
  • Taiyuan, China, 030001
    • Research Site
  • Wuhan, China, 430079
    • Research Site
  • Xi'an, China, 710061
    • Research Site
• Czechia
  • Brno, Czechia, 656 53
    • Research Site
  • Prague, Czechia, 15006
    • Research Site
• Hungary
  • Budapest, Hungary, 1122
    • Research Site
  • Budapest, Hungary, 1062
    • Research Site
  • Budapest, Hungary, 1082
    • Research Site
• Italy
  • Milan, Italy, 20141
    • Research Site
  • Milan, Italy, 20132
    • Research Site
  • Modena, Italy, 41125
    • Research Site
  • Napoli, Italy, 80131
    • Research Site
  • Padua, Italy, 35128
    • Research Site
  • Roma, Italy, 00168
    • Research Site
• Japan
  • Chūōku, Japan, 104-0045
    • Research Site
  • Kōtoku, Japan, 135-8550
    • Research Site
• Poland
  • Bydgoszcz, Poland, 85-796
    • Research Site
  • Gdansk, Poland, 80-214
    • Research Site
  • Gdynia, Poland, 81-519
    • Research Site
  • Grzepnica, Poland, 72-003
    • Research Site
  • Lodz, Poland, 90-302
    • Research Site
  • Torun, Poland, 87-100
    • Research Site
  • Warsaw, Poland, 02-781
    • Research Site
• Russia
  • Moscow, Russia, 115478
    • Research Site
  • Moscow, Russia, 117997
    • Research Site
  • Moscow, Russia, 111123
    • Research Site
  • Moscow, Russia, 143442
    • Research Site
• South Korea
  • Seoul, South Korea, 03080
    • Research Site
  • Seoul, South Korea, 03722
    • Research Site
  • Seoul, South Korea, 05505
    • Research Site
  • Seoul, South Korea, 06351
    • Research Site
• Spain
  • Barcelona, Spain, 08035
    • Research Site
  • Madrid, Spain, 28041
    • Research Site
  • Madrid, Spain, 28040
    • Research Site
  • Madrid, Spain, 28050
    • Research Site
  • Málaga, Spain, 29010
    • Research Site
  • Pozuelo de Alarcón, Spain, 28223
    • Research Site
  • Seville, Spain, 41013
    • Research Site
• Ukraine
  • Chernivtsі, Ukraine, 58013
    • Research Site
  • Ivano-Frankivsk, Ukraine, 76018
    • Research Site
  • Kyiv, Ukraine, 03022
    • Research Site
  • Uzhhorod, Ukraine, 88000
    • Research Site
• United Kingdom
  • Cambridge, United Kingdom, CB2 0QQ
    • Research Site
  • Manchester, United Kingdom, M20 4BX
    • Research Site
  • Oxford, United Kingdom, OX3 7LE
    • Research Site
  • Sutton, United Kingdom, SM2 5PT
    • Research Site
• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Research Site
    • Boston, Massachusetts, United States, 02215
      • Research Site
  • New York
    • New York, New York, United States, 10021
      • Research Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Research Site
  • Texas
    • Houston, Texas, United States, 77030
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 130 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key 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).

Key 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Module 1: AZD5305 Monotherapy; AZD5305 Monotherapy	Drug: AZD5305; Oral PARP inhibitor
Experimental: Module 2: AZD5305 + Paclitaxel; AZD5305 + Paclitaxel	Drug: AZD5305; Oral PARP inhibitor; Drug: Paclitaxel; IV Anti-microtubule agent
Experimental: Module 3: AZD5305 + Carboplatin with or without Paclitaxel; AZD5305 + Carboplatin with or without Paclitaxel	Drug: AZD5305; Oral PARP inhibitor; Drug: Paclitaxel; IV Anti-microtubule agent; Drug: Carboplatin; IV Platinum chemotherapeutic
Experimental: Module 5 AZD5305 + Datopotamab Deruxtecan; AZD5305 + Dato-DXd	Drug: AZD5305; Oral PARP inhibitor; Drug: Dato-DXd; IV Antibody-drug conjugate
Experimental: Module 6 AZD5305 + Camizestrant; AZD5305 + Camizestrant	Drug: AZD5305; Oral PARP inhibitor; Drug: Camizestrant; Oral SERD Molecule
Experimental: Module 4: AZD5305 + Trastuzumab Deruxtecan; AZD5305 + T- DXd	Drug: AZD5305; Oral PARP inhibitor; Drug: T- Dxd; IV Antibody-drug conjugate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The number of subjects with dose-limiting toxicity (DLT), as defined in the protocol.	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.	From first dose of study treatment until the end of Cycle 1.
The number of subjects with adverse events/serious adverse events	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	From time of Informed Consent to 28 + 7 days post last dose ( modules 1,2,3,5 and 6). 40+7 days post last dose for Module 4.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Best percentage change in target lesion	Change in target lesion size from baseline, as defined by RECIST 1.1.	From Screening to confirmed progressive disease (approximately 1 year)
Objective Response Rate	Best response until progression, as defined by RECIST 1.1.	From Screening to confirmed progressive disease (approximately 1 year)
Progression Free Survival	Time from C1D1 to progression or death, as defined by RECIST 1.1.	From Screening to confirmed progressive disease (approximately 1 year)
Time To Response	Time from C1D1 to complete or partial response, as defined by RECIST 1.1.	From Screening to confirmed progressive disease (approximately 1 year)
CA125 response (ovarian cancer)	at least a 50% reduction in CA125 levels from a pre-treatment sample as defined by GCIG criteria.	From Screening to confirmed progressive disease (approximately 1 year)
Module 1: Area Under Curve (AUC)	The concentration of AZD5305 in plasma will be determined. Area under the curve is the integral of the concentration-time curve. The AUC reflects the actual body exposure to drug after administration. The AUC is dependent on the rate of elimination of the drug from the body and the dose administered.	At predefined intervals throughout the treatment period (approximately 12 weeks)
Module 1: Maximum plasma concentration of the drug (Cmax)	The concentration of AZD5305 in plasma will be determined (Cmax will be derived).	At predefined intervals throughout the treatment period (approximately 12 weeks)
Module 1: The time taken to reach the maximum concentration (Tmax)	The concentration of AZD5305 in plasma will be determined (Tmax will be derived).	At predefined intervals throughout the treatment period (approximately 12 weeks)
Module 1 and Module 5: Objective Response Rate (prostate cancer)	Best response until progression, as defined by RECIST 1.1 or PCWG3 (bone)	From Screening to confirmed progressive disease (approximately 1 year)
Module 1: Radiographic progression free survival (prostate cancer)	Time from C1D1 to progression or death, as defined by RECIST 1.1 and PCWG3(bone).	From Screening to confirmed progressive disease (approximately 1 year)
Module 1: Proportion of subjects with ≥ 50% PSA decrease (prostate cancer)	PSA from baseline to the lowest post-baseline PSA result, confirmed by a second consecutive PSA assessment	From Screening to confirmed progressive disease (approximately 1 year)
Module 2: Area Under Curve (AUC)	The concentration of AZD5305 in plasma will be determined. Area under the curve is the integral of the concentration-time curve. The AUC reflects the actual body exposure to drug after administration. The AUC is dependent on the rate of elimination of the drug from the body and the dose administered.	At predefined intervals throughout the treatment period (approximately 12 weeks)
Module 2: Maximum plasma concentration of the drug (Cmax)	The concentration of AZD5305 in plasma will be determined (Cmax will be derived).	At predefined intervals throughout the treatment period (approximately 12 weeks)
Module 2: The time taken to reach the maximum concentration (Tmax)	The concentration of AZD5305 in plasma will be determined (Tmax will be derived).	At predefined intervals throughout the treatment period (approximately 12 weeks)
Module 3: Area Under Curve (AUC)	The concentration of AZD5305 in plasma will be determined. Area under the curve is the integral of the concentration-time curve. The AUC reflects the actual body exposure to drug after administration. The AUC is dependent on the rate of elimination of the drug from the body and the dose administered.	At predefined intervals throughout the treatment period (approximately 12 weeks)
Module 3: Maximum plasma concentration of the drug (Cmax)	The concentration of AZD5305 in plasma will be determined (Cmax will be derived).	At predefined intervals throughout the treatment period (approximately 12 weeks)
Module 3: The time taken to reach the maximum concentration (Tmax)	The concentration of AZD5305 in plasma will be determined (Tmax will be derived).	At predefined intervals throughout the treatment period (approximately 12 weeks)
Module 4 : Area Under Curve	The concentration of AZD5305 in plasma will be determined. Area under the curve is the integral of the concentration-time curve. The AUC reflects the actual body exposure to drug after administration. The AUC is dependent on the rate of elimination of the drug from the body and the dose administered.	At predefined intervals throughout the treatment period (approximately 12 weeks)
Module 4: Maximum plasma concentration of the drug (Cmax)	The concentration of AZD5305 in plasma will be determined (Cmax will be derived).	At predefined intervals throughout the treatment period (approximately 12 weeks)
Module 4: The time taken to reach the maximum concentration (Tmax)	The concentration of AZD5305 in plasma will be determined (Tmax will be derived).	At predefined intervals throughout the treatment period (approximately 12 weeks)
Module 4: Anti-Drug Antibody (ADA)	To investigate the presence of ADAs for T-DXd	Samples will be collected within 1 hour before dose administration on Day 1 of Cycle 1, 2, and 4, then every 4 Cycles (each cycle is 21 days), EoT, and at safety follow-up (40 days after last dose) as per Schedule of Assessments
Module 5: Area Under Curve	The concentration of AZD5305 in plasma will be determined. Area under the curve is the integral of the concentration-time curve. The AUC reflects the actual body exposure to drug after administration. The AUC is dependent on the rate of elimination of the drug from the body and the dose administered.	At predefined intervals throughout the treatment period (approximately 12 weeks)
Module 5: Maximum plasma concentration of the drug (Cmax)	The concentration of AZD5305 in plasma will be determined (Cmax will be derived).	At predefined intervals throughout the treatment period (approximately 12 weeks)
Module 5: The time taken to reach the maximum concentration (Tmax)	The concentration of AZD5305 in plasma will be determined (Tmax will be derived).	At predefined intervals throughout the treatment period (approximately 12 weeks)
Module 5: Anti-Drug Antibody (ADA)	Presence of ADAs for Dato-DXd	Whole blood samples for determination of ADA for Dato-DXd in plasma will be collected in patients receiving Dato-DXd per the schedule specified in the SoA : Day 1 of Cycle 1, 2, 4, and 8 (each cycle is 21 days) , EoT, and then 28 day follow up visit.
Module 1 : To investigate the effect of a high-fat meal on the PK of AZD5305	Effect on High fat meal on PK parameters of AZD5305.PK parameters, including but not limited to AUC and/or AUC(0-t), Cmax, Tmax, AUC(0-t) and Cmax ratio, with and without food	Cycle 0, Day 1 (C0D1), in either the "fasted" or "fed" state, followed by a single oral dose of AZD5305 in the other state for Cycle 1, Day 1 (C1D1) at least 72 hours later; 1 cycle is 28 days.
Duration of Response	Time from first response to progression or death , as defined by RECIST 1.1.	From Screening to confirmed progressive disease (approximately 1 year)
Effects of AZD5305 on pH2AX (Ser139) PD biomarker	Measure change from baseline in pH2AX	From Cycle 0 Day 1 to Cycle 1 Day 15 (approximately 21 days)
Module 4: To assess the preliminary anti-tumour activity of AZD5305 as monotherapy and in combination with T-DXd.	Time from C1D1 to progression or death, as defined by RECIST v 1.1 summarised at the 6 month landmark (PFS6)	From screening to approximately 6 months
Module 6: To characterise the PK of AZD5305 and camizestrant following a single dose and at steady state after multiple dosing, when given in combination.	Plasma concentrations and PK parameters of AZD5305 and camizestrant after single dose and multiple dose administration, including, but not limited to: AUC, Cmax, Tmax, as data allow	At predefined interval throughout the treatment (approximately 12 weeks)
Module 6: To evaluate the effect of camizestrant on the PK of AZD5305.	PK parameters, including but not limited to AUC and/or AUC(0-t), Cmax, Tmax, AUC(0-t) and Cmax ratio, with and without camizestrant.	At predefined intervals throughout the treatment period (approximately 12 weeks)
Module 6: To evaluate the effect of AZD5305 on the PK of Camizestrant.	PK parameters, including but not limited to AUC and/or AUC(0-t), Cmax, Tmax, AUC(0-t) and Cmax ratio, with and without AZD5305.	At predefined intervals throughout the treatment period (approximately 12 weeks)
Module 5: Premilinary anti tumour activity AZD5305 in combination with Dato-DXd	objective response rate and radiographic progression-free survival using RECIST v1.1. Proportion of patients achieving a ≥ 50% decrease in PSA from baseline to the post-baseline PSA result, confirmed by a second consecutive PSA assessment at least 3 weeks later (PSA50 response).	From screening to confirmed progresive disease ( approximately 12 weeks)

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: Timothy Yap, M.D. Anderson Cancer Center

Publications and helpful links

General Publications

• 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.

Helpful Links

• Breast Cancer Study Locator details (for US)

Study record dates

Study Major Dates

• Study Start (Actual): November 12, 2020
• Primary Completion (Estimated): May 28, 2027
• Study Completion (Estimated): May 28, 2027

Study Registration Dates

• First Submitted: October 26, 2020
• First Submitted That Met QC Criteria: November 19, 2020
• First Posted (Actual): November 25, 2020

Study Record Updates

• Last Update Posted (Actual): February 19, 2026
• Last Update Submitted That Met QC Criteria: February 17, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Breast Cancer; PARP inhibitor; Prostate Cancer; Pancreatic Cancer; Ovarian Cancer; AZD5305, T-DXd, Enhertu, Trastuzumab Deruxtecan, Dato-DXd, Datopotamab Deruxtecan, Camizestrant
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Intestinal Diseases; Respiratory Tract Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Intestinal Neoplasms; Rectal Diseases; Uterine Diseases; Genital Diseases, Female; Lung Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Biliary Tract Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Colonic Diseases; Lung Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Gonadal Disorders; Skin Diseases; Breast Diseases; Urologic Neoplasms; Uterine Cervical Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Uterine Neoplasms; Urinary Bladder Diseases; Skin and Connective Tissue Diseases; Prostatic Neoplasms; Stomach Neoplasms; Biliary Tract Neoplasms; Colorectal Neoplasms; Ovarian Neoplasms; Breast Neoplasms; Pancreatic Neoplasms; Carcinoma, Non-Small-Cell Lung; Uterine Cervical Neoplasms; Urinary Bladder Neoplasms; Endometrial Neoplasms; Organic Chemicals; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Coordination Complexes; Taxoids; Cyclodecanes; Diterpenes; Carboplatin; Paclitaxel; AZD5305; AZD9833
• Other Study ID Numbers: D9720C00001; 2020-002688-77 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No