Master Protocol of Dato-DXd as Monotherapy and in Combination with Anticancer Agents in Patients with Advanced/Metastatic Solid Tumours
- Conditions
- Endometrial CancerGastric CancerMetastatic Castration-resistant Prostate CancerOvarian CancerColorectal CancerUrothelial CancerBiliary Tract CancerMedDRA version: 20.0Level: SOCClassification code: 10029104Term: Neoplasms benign malignant and unspecified (incl cysts and polyps) Class: 2Therapeutic area: Diseases [C] - Neoplasms [C04]
- Registration Number
- CTIS2023-509436-26-00
- Lead Sponsor
- AstraZeneca AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 773
Male and female, = 18 years at the time of screening, 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., 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 throughout the total duration of the study and for at least 4 months after the last dose of Dato-DXd (6 months for France), in addition to the female partner using a highly effective contraception method, to prevent pregnancy in a partner. Starting at the time of first dose of Dato-DXd, male participants must not freeze or donate sperm at any time during this study and for at least 4 months after the last dose of Dato-DXd (6 months for France). Preservation of sperm should be considered prior to enrolment in this study. For substudy cohorts involving 5-FU, capecitabine, and AZD5305, at least 6 months after the last dose of these study interventions will be required., Capable of giving signed informed consent, Provision of signed and dated written Optional Genetic Research Information informed consent prior to collection of samples for optional genetic research that supports the Genomic Initiative., ***However, where specific substudy criteria differ from the master criteria below, the substudy criteria should be applied., Histologically or cytologically documented advanced or metastatic malignancy., 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., 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., 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
Any evidence of diseases such as QT prolongation and persistent toxicities associated with prior or current medication or previous anticancer therapy, Known HIV infection that is not well controlled, Known to have active tuberculosis infection, Mean resting corrected QTcF > 470 ms, regardless of gender, obtained from triplicate 12-lead ECGs performed at screening, 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 <40 years of age in first-degree relatives., Significant 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>180mmHg or diastolic BP>110mmHg), History of non-infectious ILD/pneumonitis that required steroids, current ILD/pneumonitis, or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening, Has severe pulmonary function compromised, Prior exposure to chloroquine/hydroxychloroquine without an adequate treatment washout period of > 14d prior to first dose, Receipt of live, attenuated vaccine within 30d prior to the 1st dose of the study intervention, Prior exposure to the following anticancer therapies without an adequate treatment washout period prior to enrolment: Immunotherapy non-antibody-based therapy, retinoid therapy: = 2 wks or 5 times the terminal elimination t1/2 of the chemotherapeutic agent, whichever is longer;= 6 wks for nitrosoureas or mitomycin C. Antibodybased anticancer therapy: = 4 wks, History 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, Any concurrent anticancer treatment, Palliative radiotherapy with a limited field of radiation within = 2 wks or to more than 30% of the bone marrow within = 4 wks before the first dose of study intervention, Major surgical procedure or significant traumatic injury within = 3 wks of the first dose of study intervention or an anticipated need for major surgery during the study, Prior treatment with TROP2-directed therapies, Prior treatment with other ADCs with deruxtecan payload, Previous treatment in the present study, Participation in another clinical study with a study intervention or investigational medicinal device administered in the last 4 wks prior to first dose of study intervention or concurrent enrolment in another clinical study, unless it is non-interventional clinical study or during the follow-up period of an interventional study, Severe hypersensitivity to Dato-DXd or any of the excipients, including but not limited to polysorbate 80 or other monoclonal antibodies, Involvement in the planning, conducting of the study (AZ staff and/or staff at the study site), The participant is unlikely to c
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: - To assess the efficacy of Dato-DXd as monotherapy and in combination with anticancer agents by assessment of ORR<br><br>- 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 (Substudy 3: Castration-resistant Prostate Cancer), Progression-free survival (PFS) (Substudy 4: Ovarian Cancer)
- Secondary Outcome Measures
Name Time Method Secondary end point(s):Progression-free survival (PFS);Secondary end point(s):Duration of response (DoR);Secondary end point(s):Disease control rate (DCR);Secondary end point(s):Best percentage change in tumour size;Secondary end point(s):Plasma concentrations and PK parameters, total anti-TROP2 antibody, and MAAA-1181a;Secondary end point(s):Serum concentration of durvalumab (Substudy 1), volrustomig and rilvegostomig (Substudy 6);Secondary end point(s):Plasma concentration of AZD5305 (Substudy 1, 3 and 4);Secondary end point(s):Presence of ADAs for Dato-DXd (all Substudies), Durvalumab (Substudy 2), volrustomig and rilvegostomig (Substudy 6);Secondary end point(s):Radiographic Progression-free survival (rPFS) (Substudy 3);Secondary end point(s):Time to PSA progression (Substudy 3);Secondary end point(s):CA-125 response (Substudy 4);Secondary end point(s):OS (Overall survival) (Substudy 4)