Phase I/IIa Study of AZD5335 as Monotherapy and Combination Therapy in Participants With Solid Tumors
NCT ID: NCT05797168
Last Updated: 2025-11-10
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
RECRUITING
PHASE1/PHASE2
506 participants
INTERVENTIONAL
2023-06-05
2028-01-06
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Keywords
Explore important study keywords that can help with search, categorization, and topic discovery.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
SEQUENTIAL
* Module 1 (AZD5335 monotherapy)
* Module 2 (AZD5335 in combination with saruparib)
* Module 3 (AZD5335 in combination with bevacizumab)
* Module 4 (AZD5335 in combination with carboplatin +/- bevacizumab)
* Module 5 (AZD5335 in combination with AZD9574)
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Module 1: AZD5335 Monotherapy
AZD5335 Monotherapy
AZD5335
IV Antibody-drug conjugate
Module 2: AZD5335 + Saruparib
AZD5335 + Saruparib
AZD5335
IV Antibody-drug conjugate
Saruparib (AZD5305)
Oral PARP inhibitor
Module 3: AZD5335 + Bevacizumab
AZD5335 + Bevacizumab
AZD5335
IV Antibody-drug conjugate
Bevacizumab
IV Monoclonal antibody
Module 4: AZD5335 + Carboplatin +/- Bevacizumab
AZD5335 + Carboplatin +/- Bevacizumab
AZD5335
IV Antibody-drug conjugate
Bevacizumab
IV Monoclonal antibody
Carboplatin
IV Alkylating agent
Module 5: AZD5335 + AZD9574
AZD5335 + AZD9574
AZD5335
IV Antibody-drug conjugate
AZD9574
Oral PARP inhibitor
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
AZD5335
IV Antibody-drug conjugate
Saruparib (AZD5305)
Oral PARP inhibitor
Bevacizumab
IV Monoclonal antibody
Carboplatin
IV Alkylating agent
AZD9574
Oral PARP inhibitor
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* Provision of signed and dated written Optional Genetic Research Information informed consent prior to collection of samples for optional genetic research that supports Genomic Initiative. Participants who do not provide informed consent for Optional Genetic Research may still be enrolled in the study.
* Participant must be ≥ 18 years at the time of signing the informed consent.
* Willing to provide adequate archival and/or baseline tumor sample as applicable per module-specific criteria.
* For participants who have previously received targeted therapies such as ADCs, a fresh baseline biopsy will be required unless the most recent archival tissue sample was collected after receipt of such treatment.
* Eastern Cooperative Oncology Group Performance Status of 0 or 1.
* Participants with advanced solid tumors must have received prior adequate therapy in accordance with local practice for their tumor type and stage of disease, or, in the opinion of the Investigator, a clinical trial is the best option for the next treatment based on response and/or tolerability to prior therapy. Participants with contraindications or who refuse therapy in accordance with local practice may also be considered provided that it is documented that he/she was informed about all therapeutic options.
* Participants must have measurable disease per RECIST v1.1,
1. A previously irradiated lesion can be considered a target lesion if the lesion is progressing and well defined.
2. For participants who undergo biopsies at screening and/or on treatment, it is preferred though not required, that the biopsied lesion, be distinct from any target lesion used in the RECIST v1.1 evaluation.
* Life expectancy ≥ 12 weeks.
* Adequate organ and marrow function.
* Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
(a) Male participants: (i) Male participants who are sexually active with a female partner of childbearing potential must use a male condom (plus an additional contraceptive method) post-screening through 5 months following the last dose of study intervention. It is strongly recommended for the female partner of a male participant to also use a highly effective method of contraception throughout this period. In addition, male participants must refrain from freezing or donating sperm while on study and for 5 months following the last dose of study intervention.
(b) Female participants: (i) Females of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study intervention and a negative urine or serum pregnancy test prior to starting their next cycle of treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
(ii) (ii) Sex and Contraceptive/Barrier Requirements: Highly effective birth control methods include: Total sexual abstinence is an acceptable method provided it is the usual lifestyle of the participant (defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments) \[(periodic abstinence e.g., calendar, ovulation, symptothermal, post-ovulation methods), declaration of abstinence for the duration of exposure to study intervention, and withdrawal are not acceptable methods of contraception\], a vasectomized partner, Implanon®, bilateral tubal occlusion, intrauterine device/levonorgestrel intrauterine system, Depo Provera™ injections, oral contraceptive associated with inhibition of ovulation, and Evra Patch™, Xulane™, or NuvaRing®.
Female participants of childbearing potential who are sexually active with a non-sterilized male partner must agree to use one highly effective method of birth control (defined as one that can achieve a failure rate of less than 1% per year when used consistently and correctly), from enrolment throughout the study and for 8 months following the last dose of study intervention. The male partner of a female participant of childbearing potential must also use a male condom (plus spermicide, if available) throughout this period. Cessation of contraception after this point should be discussed with a responsible physician. In addition, female participants must not donate or retrieve for their own use, ova while on study and for 8 months following the last dose of study intervention.
Exclusion Criteria
* Patients with brain metastases unless, asymptomatic, stable, and not requiring continuous corticosteroids at a dose of \> 10 mg prednisone/day or equivalent for at least 4 weeks prior to first dose of study intervention.
* Treatment with any of the protocol defined medications, without adequate washout periods or time before the first dose of study intervention.
* Unresolved toxicities of Grade ≥ 2 (National Cancer Institute \[NCI\] CTCAE v5.0) from prior therapy (excluding vitiligo, alopecia, and endocrine disorders that are controlled with replacement hormone therapy). Participants with stable ≤ Grade 2 neuropathy are eligible.
* Active infection, including tuberculosis and infections with hepatitis B virus (HBV; verified by known positive hepatitis B surface antigen \[HBsAg\] result), hepatitis C virus (HCV) or known HIV infection that is not well controlled. All of the following criteria are required to define an HIV infection that is well controlled: undetectable viral RNA, CD4+ count ≥ 350/mm3, no history of acquired immune deficiency syndrome-defining opportunistic infection within the past 12 months, and stable for at least 4 weeks on the same anti-HIV medications (meaning there are no expected further changes in that time to the number or type of antiretroviral drugs in the regimen).
Patients with a past or resolved HBV/HCV infection are eligible if:
1. Negative for HBsAg and positive for anti-hepatitis B virus core protein (HBc) or
2. Are HBsAg + with chronic HBV infection (lasting 6 months or longer) and meet conditions i-iii below:
(i) HBV DNA viral load \<100 IU/mL. (ii) Have normal transaminase values, or, if liver metastases are present, abnormal transaminases, with a result of aspartate aminotransferase (AST)/alanine aminotransferase (ALT) \<3 x upper limit of normal (ULN), which are not attributable to HBV infection.
(iii) Start or maintain antiviral treatment if clinically indicated as per the Investigator or as per local guideline.
Note for Japan: Japanese patients with positive anti-HBs/anti-HBc and negative HBsAg will be assessed following local guidelines.
(c) Participants testing positive for HCV antibody are eligible only if the polymerase chain reaction test result is negative for HCV RNA.
* Patient has ILD/pneumonitis or has a history of (non-infectious) ILD/pneumonitis that required oral or IV steroids or supplemental oxygen, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
* Patients with a history of radiation pneumonitis which has clinically and radiologically resolved and not requiring treatment with steroids may be eligible.
* History of another malignancy except for:
* Malignancy treated with curative intent and with no known active disease for at least 2 years prior to screening of study intervention and with low potential risk for recurrence.
* Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
* Adequately treated carcinoma in situ without evidence of disease.
* Localized non-invasive solid organ primary disease under surveillance.
* Patients with any of the following cardiac criteria:
* History of arrhythmia (such as multifocal premature ventricular contractions, bigeminy, trigeminy, and ventricular tachycardia), which is symptomatic or requires treatment NCI CTCAE v5.0 Grade 3 except for:
(i) Rate controlled asymptomatic atrial fibrillation.
* NOTE: significant abnormalities in serum electrolytes that can increase the risk of arrhythmic events (ie, sodium, potassium, calcium, and magnesium) should be corrected before starting the study intervention.
* Uncontrolled hypertension.
* Acute coronary syndrome/acute myocardial infarction, unstable angina pectoris, coronary intervention procedure with percutaneous coronary intervention, or coronary artery bypass grafting within 6 months of screening.
* History of brain perfusion problems (eg, carotid stenosis) or stroke, or transient ischemic attack in the last 6 months prior to screening.
* Symptomatic heart failure (as defined by New York Heart Association class ≥ 2).
* Prior or current diagnosis of cardiomyopathy considered clinically relevant per investigator's judgement.
* Severe uncorrected valvular heart disease.
* Mean resting QTcF \> 470 msec obtained from triplicate electrocardiograms (ECGs) and averaged, recorded within 5 minutes.
* Any factor that, in the opinion of the investigator, increases the proarrhythmic risk of QT prolongation, such as congenital long QT syndrome, family history of long QT syndrome, hypertrophic cardiomyopathy, or unexplained sudden cardiac death under 40 years of age.
* Uncontrolled and/or unresolved intercurrent illness within 12 months prior to screening, including but not limited to serious chronic gastrointestinal conditions associated with diarrhea, or illness (including psychiatric illness) and/or social situations, in the opinion of the investigator, that would limit compliance with study requirements and activities, substantially increase risk of incurring AEs or compromise the ability of the participant to give written informed consent.
* Substance abuse or any other medical conditions that would increase the safety risk to the participant or interfere with participation of the participant or evaluation of the clinical study in the opinion of the Investigator.
* Receipt of live attenuated vaccine within 30 days prior to the first dose of study intervention. Note: Participants, if enrolled, should not receive live vaccine whilst receiving study intervention and up to 3 months after the last dose of study intervention. Participants can receive Coronavirus (COVID)-19 vaccines, at the discretion of the Investigator, following a benefit/risk evaluation for the individual participant and in accordance with local rules and regulations and vaccination guidelines. Note: If a COVID-19 vaccine is administered it should be done \> 72 hours prior to study intervention initiation or after completion of the DLT period.
* For women only - currently pregnant (confirmed with positive pregnancy test or suspected), lactating, breastfeeding, or intention to become pregnant during the study period.
* Concurrent enrolment in another clinical study, unless it is an observational (non interventional) clinical study or during the follow-up period of an interventional study.
* Patients with a known hypersensitivity to study intervention or any of the excipients of the product.
* Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
* Judgment by the Investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements.
* Previous enrolment in the present study. \*\*Other module specific criteria may apply
18 Years
130 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
AstraZeneca
INDUSTRY
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Funda Meric-Bernstam, MD
Role: PRINCIPAL_INVESTIGATOR
UT MD Anderson Cancer Center
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Research Site
Duarte, California, United States
Research Site
Irvine, California, United States
Research Site
La Jolla, California, United States
Research Site
Aurora, Colorado, United States
Research Site
Louisville, Kentucky, United States
Research Site
Boston, Massachusetts, United States
Research Site
Detroit, Michigan, United States
Research Site
Columbus, Ohio, United States
Research Site
Portland, Oregon, United States
Research Site
Providence, Rhode Island, United States
Research Site
Providence, Rhode Island, United States
Research Site
Houston, Texas, United States
Research Site
Fairfax, Virginia, United States
Research Site
Liverpool, , Australia
Research Site
Melbourne, , Australia
Research Site
Edmonton, Alberta, Canada
Research Site
London, Ontario, Canada
Research Site
Toronto, Ontario, Canada
Research Site
Montreal, Quebec, Canada
Research Site
Montreal, Quebec, Canada
Research Site
Chengdu, , China
Research Site
Chongqing, , China
Research Site
Guangzhou, , China
Research Site
Guangzhou, , China
Research Site
Jinan, , China
Research Site
Xi'an, , China
Research Site
Zhengzhou, , China
Research Site
Berlin, , Germany
Research Site
Essen, , Germany
Research Site
Freiburg im Breisgau, , Germany
Research Site
Hanover, , Germany
Research Site
Leipzig, , Germany
Research Site
Mannheim, , Germany
Research Site
Regensburg, , Germany
Research Site
Haifa, , Israel
Research Site
Ramat Gan, , Israel
Research Site
Hidaka-shi, , Japan
Research Site
Kashiwa, , Japan
Research Site
Kōtoku, , Japan
Research Site
Sunto-gun, , Japan
Research Site
Tokyo, , Japan
Research Site
Seoul, , South Korea
Research Site
Seoul, , South Korea
Research Site
Barcelona, , Spain
Research Site
Madrid, , Spain
Research Site
Madrid, , Spain
Research Site
Málaga, , Spain
Research Site
Taichung, , Taiwan
Research Site
Tainan, , Taiwan
Research Site
Taipei, , Taiwan
Research Site
Taipei, , Taiwan
Research Site
Ankara, , Turkey (Türkiye)
Research Site
Ankara, , Turkey (Türkiye)
Research Site
Ankara, , Turkey (Türkiye)
Research Site
Istanbul, , Turkey (Türkiye)
Research Site
Cambridge, , United Kingdom
Research Site
Glasgow, Scotland, , United Kingdom
Research Site
London, , United Kingdom
Research Site
London, , United Kingdom
Research Site
Sutton, , United Kingdom
Countries
Review the countries where the study has at least one active or historical site.
Central Contacts
Reach out to these primary contacts for questions about participation or study logistics.
AstraZeneca Clinical Study Information Center
Role: CONTACT
Phone: 1-877-240-9479
Email: [email protected]
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
2022-502576-23-00
Identifier Type: REGISTRY
Identifier Source: secondary_id
D8990C00001
Identifier Type: -
Identifier Source: org_study_id