Master Protocol of Dato-DXd as Monotherapy and in Combination with Anticancer Agents in Patients with Advanced/Metastatic Solid Tumours
- Conditions
- various Advanced/Metastatic solid tumour types- Endometrial Cancer - Gastric Cancer - Ovarian Cancer- Metastatic castration-resistant prostate cancer- Colorectal cancer- Urothelial Cancer- Biliary Tract CancerMedDRA version: 12.0Level: HLGTClassification code 10007129Term: Cancer-related morbiditiesSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2022-000776-19-PL
- Lead Sponsor
- AstraZeneca AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 670
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. All participants must provide an archival FFPE tumour sample or newly acquired FFPE tumour sample for tissue-based analysis (see Section 8.6.1.1 for further details).
4- All participants must provide an archival FFPE tumour sample or
newly acquired FFPE tumour sample for tissue-based analysis.
5- 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.
6- Adequate bone marrow reserve and organ function within 7 days before randomization/treatment assignment defined as:
-Haemoglobin = 9.0 g/dL (red blood cell/plasma transfusion or red blood cell stimulating factor, such as erythropoietin, is not allowed within 1 week prior to screening assessment)
-Absolute neutrophil count = 1.5 × 109/L (granulocyte colony stimulating factor administration is not allowed within 1 week prior to screening assessment).; pegylated granulocyte colony stimulating factor is not allowed within 2 weeks prior to screening assessment).
-Platelet count =100 × 109/L (platelet transfusion or platelet stimulating factor, such as thrombopoietin, 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 or < 3 × ULN in the presence of documented
Gilbert's syndrome.
-Except in the setting of HBV, ALT and AST = 3 × ULN (< 5 × ULN in participants with liver metastases). See Exclusion Criterion 8 for
requirements in the setting of HBV.
-Calculated CrCL = 30 mL/min
7- Minimum life expectancy of 12 weeks.
8- 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.
9- All women of childbearing potential must have a negative pregnancy test (serum) documented during screening.
10- Female participants must be 1 year post-menopausal, surgically sterile, or using 1 highly effective form of birth control. Women of
childbearing potential must agree to use 1 highly effective method of birth control or avoid intercourse. 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 of Dato-DXd. Starting at the time of first dose of Dato-DXd, female participants must not donate, or retrieve for their own use, ova at
any time during this study and for at least 7 months after the last dose of Dato-DXd.
Preservation of ova should be considered prior to enrolment in this study.
11- Male participants who intend to be sexually active with a female partner of childbearing potential must be surgically sterile, avoid
intercourse, or using a highly effective method of contraception from the time of screening throu
1Any evidence of diseases such as QT prolongation and persistent toxicities associated with prior or current medication or previous anti-cancer therapy
2History of another primary malignancy except that treated with curative intent with no known active disease within 3 yrs before the first dose of study intervention and of low potential risk for recurrence 3Persistent toxicities caused by previous anticancer therapy, excluding alopecia, not yet improved to Grade=1 or baseline
4Participants with irreversible toxicity that is not reasonably expected to be exacerbated by study intervention in opinion of PI may be included (eg, hearing loss)
5Spinal 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
6Leptomeningeal carcinomatosis
7Clinically significant corneal disease
8Active hepatitis or uncontrolled hepatitis B or C virus infection
9Uncontrolled infection requiring IV antibiotics, antivirals or antifungals eg, prodromal symptoms
10Known HIV infection that is not well controlled
11Known to have active tuberculosis infection
12 Mean resting corrected QTcF > 470 ms, regardless of gender, obtained from triplicate 12-lead ECGs performed at screening.
13History 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.
14Significant cardiac diseases including:
MI or uncontrolled/unstable angina within 6 months before enrolment.
CHF (NYHA 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 BP>180 mmHg or diastolic BP>110 mmHg)
15History 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
16Has severe pulmonary function compromised
17Prior exposure to chloroquine/hydroxychloroquine without an adequate treatment washout period of > 14 days prior to first dose
18Receipt of live, attenuated vaccine within 30 days prior to the first dose of the study intervention
19Prior exposure to the following anticancer therapies without an adequate treatment washout period prior to enrolment:Immunotherapy non-antibody-based therapy, retinoid therapy: = 2 weeks or 5 times the terminal elimination t1/2 of the chemotherapeutic agent, whichever is longer;= 6 weeks for nitrosoureas or mitomycin C. Antibody-based anticancer therapy: = 4 weeks
20Any concurrent anticancer treatment
21Palliative radiotherapy with a limited field of radiation within = 2 weeks or to more than 30% of the bone marrow within = 4 weeks before the first dose of study intervention
22Major surgical procedure o
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method