Study of Dato-Dxd as Monotherapy and in Combination With Anti-cancer Agents in Patients With Advanced Solid Tumours (TROPION-PanTumor03)

JRCT ID: jRCT2031220404

Registered date:21/10/2022

Basic Information

• Recruitment status: Recruiting

Health condition(s) or Problem(s) studied

Endometrial CA
Gastric CA
Prostate CA
Ovarian CA
Colorectal CA
Urothelial CA
Biliary Tract CA

• Date of first enrollment: 10/02/2023
• Target sample size: 582
• Countries of recruitment: Canada,Japan,China,Japan,France,Japan,Germany,Japan,Italy,Japan,Korea,Japan,Poland,Japan,Spain,Japan,Switzerland,Japan,Taiwan,Japan,Turkey,Japan,United Kingdom,Japan,United States,Japan
• Study type: Interventional

Intervention(s)

Substudy-1A: Dato-DXd
Substudy-2A: Dato-DXd, Capecitabine
Substudy-2B: Dato-DXd, 5-Fluorouracil
Substudy-3A: Dato-DXd
Substudy-3C: Dato-DXd, Prednisone/prednisolone
Substudy-4A: Dato-DXd
Substudy-4C: Dato-DXd, Carboplatin, Bevacizumab
Substudy-5A: Dato-DXd
Substudy-5B: Dato-DXd, 5-Fluorouracil, Leucovorin LV, Bevacizumab or Dato-DXd, Capecitabine, Bevacizumab
Substudy-6A: Dato-DXd, Volrustomig
Substudy-6B: Dato-DXd, Rilvegostomig
Substudy-6C: Dato-DXd
Substudy-6D: Dato-DXd, Carboplatin or Cisplatin
Substudy-7A: Dato-DXd

Outcome(s)

Primary Outcome

Objective response rate (ORR)
The number of subjects with adverse events/serious adverse events
PSA50 response (Substudy 3 only)
Progression free survival (PFS) response (Substudy 4C only)

Secondary Outcome

Progression free survival (PFS)
Duration Of Response (DoR)
Disease Control Rate (DCR)
Best percentage change in tumour size
Pharmacokinetics of Dato-DXd (all substudies) and volrustomig and rilvegostomig (substudy 6): Maximum plasma concentration of the drug (Cmax)
Pharmacokinetics of Dato-DXd (all substudies) and volrustomig and rilvegostomig (substudy 6): The time taken to reach the maximum concentration (Tmax)
Pharmacokinetic Parameter of Dato-DXd (all substudies) and volrustomig and rilvegostomig (substudy 6): Area under the plasma concentration- time curve (AUC)
Plasma concentration of Total anti-TROP2 antibody
Plasma concentration of MAAA-1181a
Anti Drug Antibody (ADA) for Dato-DXd (all substudies) and volrustomig and rilvegostomig (substudy 6)
Radiographic PFS (Substudy 3)
PSA progression (Substudy 3)
CA-125 response (Substudy 4)
Overall survival (OS) (Substudy 4)

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: <= 130age old
• Gender: Both

Include criteria

Male and female, >= 18 years
Documented advanced or metastatic malignancy
Eastern Cooperative Oncology Group performance status of 0 or 1 with no deterioration over the 2 weeks prior to baseline or day of first dosing
All participants must provide a tumour sample for tissue-based analysis
At least 1 measurable lesion not previously irradiated, except Substudy 3 (Prostate Cancer) which allows participants with non measurable bone metastatic disease
Adequate bone marrow reserve and organ function
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 serum pregnancy test documented during screening
Female participants must be 1 year post-menopausal, surgically sterile, or using 1 highly effective form of birth control. Female participants must not donate, or retrieve for their own use, ova at any time during this study
Male participants who intend to be sexually active with a female partner of childbearing potential must be surgically sterile, avoid intercourse, or use a highly effective method of contraception. Male participants must not freeze or donate sperm at any time during this study.
Capable of giving signed informed consent
Provision of signed and dated written optional genetic research informed consent prior to collection of samples for optional genetic research that supports the Genomic Initiative

Exclude criteria

Any evidence of diseases which, in the investigator's opinion, makes it undesirable for the participant to participate in the study or that would jeopardize compliance with the protocol
History of another primary malignancy except for adequately resected basal cell carcinoma or in situ squamous cell carcinoma of the skin, or other solid malignancy treated with curative intent
Persistent toxicities caused by previous anticancer therapy, excluding alopecia, not yet improved
Irreversible toxicity that is not reasonably expected to be exacerbated by study intervention in the opinion of the investigator, for example hearing loss
Spinal cord compression or brain metastases unless treated
Leptomeningeal carcinomatosis
Clinically significant corneal disease
Active hepatitis or uncontrolled hepatitis B or C virus infection
Uncontrolled infection requiring IV antibiotics, antivirals or antifungals, for example prodromal symptoms
Known HIV infection that is not well controlled
Known active tuberculosis infection
Mean resting corrected QTcF > 470 ms
In the judgement of the investigator, history of QT prolongation associated with other medications that required discontinuation of that medication, or any current concomitant medication known to prolong the QT interval and cause TdP
In the judgement of the investigator, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age in first-degree relatives
Uncontrolled or significant cardiac diseases
History of non-infectious Interstitial lung disease (ILD)/pneumonitis that required steroids
Has severe pulmonary function compromise
Prior exposure to chloroquine/hydroxychloroquine without an adequate treatment washout period
Receipt of live, attenuated vaccine within 30 days prior to the first dose of study intervention
Prior exposure to anticancer therapies without an adequate treatment washout period prior to enrolment or any concurrent anticancer treatment
Palliative 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
Major surgical procedure or significant traumatic injury within <= 3 weeks of the first dose of study intervention or an anticipated need for major surgery during the study
Prior treatment with TROP2-directed therapies or other antibody-drug conjugate (ADCs) with deruxtecan payload
Herbal or natural products intended as treatment or prophylaxis for any type of cancer that may interfere with the activity of the study intervention
Previous treatment in the present study
Participation in another clinical study with a study intervention or investigational medicinal device administered in the last 4 weeks prior to first dose of study intervention or concurrent enrolment in another clinical 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 and/or conduct of the study
Judgment by the investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions, and requirements
Females that are pregnant, breastfeeding, or planning to become pregnant
Female participants should refrain from breastfeeding from enrolment throughout the study and for at least 7 months after last dose of Dato-DXd

Related Information

• Primary Sponsor: Inoguchi Akihiro
• Secondary Sponsor: AstraZeneca
• Secondary ID(s): NCT05489211