A Phase II, Multicentre, Open-label, Master Protocol to Evaluate the Efficacy and Safety of Datopotamab Deruxtecan (Dato-DXd) as Monotherapy and in Combination With Anticancer Agents in Patients With Advanced/Metastatic Solid Tumours

D926UC00001

TROPION-PanTumor03 will investigate the safety, tolerability, and anti-tumour activity of Datopotamab Deruxtecan (Dato-DXd) as Monotherapy and in Combination with Anticancer Agents in Patients with Advanced/Metastatic Solid Tumours.

2022-09-06

2026-08-19

2026-08-19

Recruiting

Early phase I

531

Key Inclusion 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 Key Exclusion 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 * 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 * Active TB infection * 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 * 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 Anti-drug antibody, ADC Antibody-drug conjugate (ADCs), other ADCs with deruxtecan payload * Severe hypersensitivity to monoclonal antibodies * Pregnant, breastfeeding, planning to become pregnant

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2'], 'designInfo': {'allocation': 'NON_RANDOMIZED', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'Within each substudy, Dato-DXd will be evaluated as monotherapy (all except #2 Gastric Cancer and #6 Urothelial Cancer) and in combination with approved or novel anticancer agents that may be active in the tumour type being evaluated (all except #7 Biliary Tract Cancer). All substudies will be treatment assigned.\n\nSubstudy 1 (Endometrial): MONO: Dato-DXd monotherapy; COMBO; Dato-DXd + durvalumab, Dato-DXd + Saruparib, Dato-DXd + durvalumab +Saruparib\n\nSubstudy 2 (Gastric): Dato-DXd + capecitabine, Dato-DXd + 5-FU, Dato-DXd + capecitabine/ 5-FU + volrustomig\n\nSubstudy 3 (mCRPC): MONO; COMBO: Dato-DXd + AZD5305, Dato-DXd + prednisone/prednisolone\n\nSubstudy 4 (Ovarian): MONO; COMBO: Dato-DXd + carboplatin --\\> Dato-DXd + Saruparib\n\nSubstudy 5 (CRC): MONO; COMBO Dato-DXd + 5-FU + leucovorin + bevacizumab or Dato-DXd + capecitabine + bevacizumab\n\nSubstudy 6 (Urothelial): Dato-DXd + volrustomig, Dato-DXd + rilvegostomig\n\nSubstudy 7 (BTC): MONO', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE', 'maskingDescription': 'The study is open label. Patients will be assigned treatment in all Substudies.'}}, 'enrollmentInfo': {'count': 531, 'type': 'ESTIMATED'}}

2024-04-25