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Master Protocol of Dato-DXd as Monotherapy and in Combination with Anticancer Agents in Patients with Advanced/Metastatic Solid Tumours
EU CTIS ID: 2023-509436-26-00
What this study is testing
- 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
- Therapeutic exploratory (Phase II)
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- 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 or capecitabine, 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.
You likely can't join if
- Any evidence of diseases such as QT prolongation and persistent toxicities associated with prior or current medication or previous anticancer therapy
- Known HIV infection unless well controlled (according to protocol-specific definitions, e.g., stable on antiretroviral therapy, undetectable viral load).
- 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.
- History of drug-induced QT prolongation requiring discontinuation, current use of medications known to prolong QT and cause torsades de pointes, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death in a first-degree relative aged <40.
See the full eligibility criteria
Who can join
- 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 or capecitabine, 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 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
- Minimum life expectancy of 12 weeks.
- 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.
- All women of childbearing potential must have a negative pregnancy test (serum) documented during screening.
What rules you out
- Any evidence of diseases such as QT prolongation and persistent toxicities associated with prior or current medication or previous anticancer therapy
- Known HIV infection unless well controlled (according to protocol-specific definitions, e.g., stable on antiretroviral therapy, undetectable viral load).
- 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.
- History of drug-induced QT prolongation requiring discontinuation, current use of medications known to prolong QT and cause torsades de pointes, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death in a first-degree relative aged <40.
- 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 within 3 years prior to the first dose, except for those treated with curative intent and with no known active disease and low risk of recurrence (e.g., adequately treated basal cell carcinoma, squamous cell carcinoma, or carcinoma in situ).
- 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 comply with study procedures, restrictions and requirements.
- Persistent toxicities (excluding alopecia) from previous anticancer therapy that have not improved to Grade ≤1 or baseline, according to CTCAE v5.0
- Pregnant, breastfeeding, planning to become pregnant
- Herbal or natural products intended as treatment or prophylaxis for any type of cancer that may interfere with the activity of the study intervention are excluded, see AI2
- Female participants should refrain from breastfeeding from enrolment throughout the study and for at least 7 months after last dose of Dato-DXd
- Participants legally protected cannot be included
- *However, where specific substudy criteria differ from the master criteria below, the substudy criteria should be applied
- Participants with irreversible toxicities (e.g., hearing loss) not reasonably expected to be exacerbated by study intervention may be eligible at the investigator’s discretion.
- Spinal cord compression or brain metastases unless treated, asymptomatic, stable, and not requiring steroids for at least 4 wks prior to randomisation/start of study intervention. A min 2 wks must have elapsed between the end of whole brain radiotherapy/stereotactic radiation and study enrolment
- Leptomeningeal carcinomatosis
- Clinically significant corneal disease
- Active hepatitis B or C infection (unless controlled as per protocol requirements), or any other uncontrolled chronic hepatitis.
- Uncontrolled infection requiring IV antibiotics, antivirals or antifungals eg, prodromal symptoms
The study team makes the final eligibility decision.
Where it's taking place
- China
- Korea, Republic of
- United Kingdom
- United States
- Canada
- Taiwan
- Turkey
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 65+ years, 18-64 years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include China; Korea, Republic of; United Kingdom; United States; Canada; Taiwan and 1 more location(s). Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.