various Advanced/Metastatic solid tumour types - Endometrial Cancer - Gastric Cancer - Ovarian Cancer - Metastatic castration-resistant prostate cancer - Colorectal cancer MedDRA version: 12.0 Level: HLGT Classification code 10007129 Term: Cancer-related morbidities System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Code: AZD5305
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: N/A
CAS Number: 2589531-76-8
Current Sponsor code: AZD5305
Concentration unit: mg milligram(s)
Concentration type: ra
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1- Male and female, = 18 years at the time of screening 2-Histologically or cytologically documented advanced or metastatic malignancy. 3- Eastern Cooperative Oncology Group performance status of 0 or 1 with no deterioration over the previous 2 weeks prior to baseline or day of first dosing. Archival FFPE tumour samples must be < 12 months old from the time of collection to the time of start of protocol screening. The exception is for gastric Substudy Cohorts 2A and 2B, where prospective PD-L1 central testing is required for enrolment, archival FFPE tumour samples must be < 6 months old from the time of collection to the time of start of protocol. 4- At least 1 lesion not previously irradiated that qualifies as a RECIST 1.1 target lesion at baseline and can be accurately measured at baseline as = 10 mm in the longest diameter (except lymph nodes, which must have short axis = 15 mm) with CT or MRI and is suitable for accurate repeated measurements. Substudy 3 (mCRPC) allows enrolment of participants with nonmeasurable (by RECIST 1.1) bone metastatic disease. 5- Adequate bone marrow reserve and organ function within 7 days before randomization/treatment assignment defined as: -Haemoglobin = 9.0 g/dL -Absolute neutrophil count = 1.5 × 109/L -Platelet count =100 × 109/L (platelet transfusion is not allowed within 1 week prior to screening assessment). -Serum albumin = 2.5 g/dL, -International normalised ratio/prothrombin time and either partial thromboplastin time or activated partial thromboplastin time = 1.5 × ULN. -Total bilirubin = 1.5 × ULN if no liver metastases or < 3 × ULN in the presence of documented Gilbert’s syndrome or liver metastases at baseline. -ALT and AST = 3 × ULN (< 5 × ULN in participants with liver metastases). -Calculated CrCL = 30 mL/min 6 Minimum life expectancy of 12 weeks. 7- At the time of screening, contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. 8- Negative pregnancy test (serum) for women of childbearing potential who are sexually active with a non-sterilised male partner. 9- Female participants must be 1 year post-menopausal, surgically sterile, or using 1 highly effective form of birth control. Women of childbearing potential who are sexually active with a non-sterilised male partner must agree to use 1 highly effective method of birth control. They should have been stable on their chosen method of birth control for a minimum of 3 months before entering the study and continue for at least 7 months after the last dose. 10- Male participants who intend to be sexually active with a female partner of childbearing potential must be surgically sterile or using a highly effective method of contraception from the time of screening throughout the total duration of the study and for drugs that are potentially genotoxic the drug washout period (at least 4 months after the last dose of study intervention) to prevent pregnancy in a partner. Male participants must not donate or bank sperm during this same time period. 11-Capable of giving signed informed consent 12 Provision of signed and dated written Optional Genetic Research Information informed consent prior to collection of sample for optional genetic research that supports Genomic Initiative. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this
Exclusion criteria
Exclusion criteria: 1-Any evidence of diseases such as QT prolongation and persistent toxicities associated with prior or current medication or previous anti-cancer therapy 2-History of another primary malignancy except that treated with curative intent with no known active disease within 3 years before the first dose of study intervention and of low potential risk for recurrence 3-Persistent toxicities caused by previous anticancer therapy, excluding alopecia, not yet improved to Grade = 1 or baseline 4-Participants with irreversible toxicity that is not reasonably expected to be exacerbated by study intervention may be included (eg, hearing loss) after consultation with the AstraZeneca study clinical lead 5-Spinal cord compression or brain metastases unless treated, asymptomatic, stable, and not requiring steroids for at least 4 weeks prior to randomisation/start of study intervention. A minimum of 2 weeks must have elapsed between the end of whole brain radiotherapy/stereotactic radiation and study enrolment 6-Leptomeningeal carcinomatosis 7-Clinically significant corneal disease 8-Active hepatitis or uncontrolled hepatitis B or C virus infection 9-Uncontrolled infection requiring IV antibiotics, antivirals or antifungals eg, prodromal symptoms 10- Known HIV infection that is not well controlled 11-Known to have active tuberculosis infection 12- Mean resting corrected QTcF > 470 ms, regardless of gender, obtained from triplicate 12-lead ECGs performed at screening. 13- History of QT prolongation associated with other medications that required discontinuation of that medication, any current concomitant medication known to prolong the QT interval and cause TdP. Congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age in first-degree relatives. 14-Significant cardiac diseases including: - Myocardial infarction or uncontrolled/unstable angina within 6 months before enrolment. - Congestive heart failure (New York Heart Association Class II to IV). - Cardiac arrhythmia, multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia, which is symptomatic or requires treatment (CTCAE Grade 3), symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. Participants with atrial fibrillation controlled by medication or arrhythmias controlled by pacemakers may be permitted upon discussion with the study clinical lead. - Uncontrolled hypertension (resting systolic blood pressure > 180 mmHg or diastolic blood pressure > 110 mmHg) 15-History of non-infectious ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or has suspected ILD/pneumonitis that cannot be ruled out by imaging at screening 16-Clinically severe pulmonary function (ie, pulmonary emboli within 3 months prior to study enrolment, severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease, pleural effusion etc); or any autoimmune, connective tissue or inflammatory disorders (ie, rheumatoid arthritis, Sjögren’s syndrome, sarcoidosis, etc) 17-Prior exposure to chloroquine/hydroxychloroquine without an adequate treatment washout period of > 14 days prior to first dose 18-Receipt of live, attenuated vaccine within 30 days prior to the first dose of the study intervention 19-Prior exposure to the following anticancer therapies without an adequate treatment washout period prior to enrolment: Immunotherapy n
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: -To assess the efficacy of Dato-DXd as monotherapy and in combination with anticancer agents by assessment of ORR -To assess the safety and tolerability of Dato-DXd as monotherapy and in combination with anticancer agents;Secondary Objective: - To further assess the efficacy of Dato-DXd as monotherapy and in combination with anticancer agents by assessment of PFS, DoR, DCR at 12 and 24 weeks, Best percentage change in tumour size (where applicable) - To assess the PK of Dato-DXd, total anti-TROP2 antibody, and MAAA-1181a in plasma - To investigate the immunogenic potential of Dato-DXd;Primary end point(s): - Objective response rate (ORR) - AEs/SAEs, ECOG performance status, changes from baseline in laboratory findings,ECGs, vital signs, physical examinations, and ophthalmologic assessments - PSA50 response - Progression-free survival (PFS);Timepoint(s) of evaluation of this end point: - ORR, PSA50, PFS: data obtained from first dose up until progression per RECIST 1.1 as assessed by the investigator or death, or the last evaluable assessment in the absence of an event (regardless of whether the participant withdraws from therapy) - Safety: during the study treatment or the safety follow-up period (defined as 28 days after last dose of study intervention, or if durvalumab, nivolumab, or bevacizumab is given, 90 days after the last dose will be reported) but prior to subsequent cancer therapy | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Progression-free survival (PFS) - Duration of response (DoR) - Disease control rate (DCR) - Best percentage change in tumour size - Overall survival (OS) - Radiographic Progression-free survival (rPFS) - CA-125 response - Plasma concentrations and PK parameters, total anti-TROP2 antibody, and MAAA-1181a - Presence of ADAs for Dato-DXd;Timepoint(s) of evaluation of this end point: - PFS, DoR, DCR, Best percentage change in tumour size, rPFS, CA-125 response: data obtained from first dose up until progression per RECIST 1.1 as assessed by the investigator or death, or the last evaluable assessment in the absence of an event (regardless of whether the participant withdraws from therapy) - OS: data obtained from first dose up until death, or the last evaluable assessment in the absence of an event - PK and Immunogenicity: blood samples will be taken for specific drugs at limited time points | — |
Countries
Canada, China, France, Germany, Italy, Japan, Korea, Republic of, Poland, Spain, Switzerland, Taiwan, Turkey, United Kingdom, United States
Contacts
Public ContactInformation Center
AstraZeneca AB
Outcome results
None listed