Status and phase
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About
This research is designed to determine if experimental treatment with Antibody-drug conjugate, AZD5335, alone, or in combination with anti-cancer agents is safe, tolerable, and has anti-cancer activity in patients with advanced tumors
Full description
This study is a Phase I/IIa modular, open-label, multi-center study of AZD5335 administered either as monotherapy or in combination with other anti-cancer agents in participants with advanced solid malignancies
Enrollment
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Volunteers
Inclusion and exclusion criteria
Core Inclusion Criteria:
Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form and in this protocol.
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.
Consent to provide adequate baseline tumor sample, as applicable per module-specific criteria.
Participant must be ≥ 18 years at the time of signing the informed consent.
Willing to provide archival or baseline tumor sample.
For participants who have previously received targeted therapies such as ADCs, a fresh baseline biopsy will be required.
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,
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) Non-sterilized male participants who are sexually active with a female partner of childbearing potential must use a male condom (plus spermicide, if available) post-screening through 5 half-lives (45 days) plus 6 months (approximately 7.5 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 sperm donation while on study and for 5 half lives (45 days) plus 6 months (~7.5 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.
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 5 half-lives (45 days) plus 6 months (In total, 7.5 months) following the last dose of study intervention. It is strongly recommended for the male partner of a female participants to also use 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 refrain from egg donation while on study and for 5 half-lives (45 days) plus 6 months (~7.5 months) following the last dose of study intervention.
Core Exclusion Criteria:
Patients with a past or resolved HBV/HCV infection are eligible if:
(a) Negative for HBsAg and positive for anti-HBc or (b) 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 AST/ALT <3 × 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.
History of another primary malignancy except for:
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); symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia.
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 cardiomyopathy.
Severe valvular heart disease.
Mean resting QTcF > 470 msec obtained from triplicate ECGs and averaged, recorded within 5 minutes.
Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age.
Uncontrolled intercurrent illness within 12 months prior to screening, including but not limited to serious chronic GI conditions associated with diarrhea, or psychiatric illness/social situations 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 30 days 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), lactating, breastfeeding, or intend 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
Primary purpose
Allocation
Interventional model
Masking
150 participants in 2 patient groups
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Central trial contact
AstraZeneca Clinical Study Information Center
Data sourced from clinicaltrials.gov
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