Study of Dato-Dxd as monotherapy and in combination with anti-cancer agents in patients with advanced solid Tumours (TROPION-PanTumor03)

Study identifier:D926UC00001

ClinicalTrials.gov identifier:NCT05489211

EudraCT identifier:2022-000776-19

CTIS identifier:N/A

Recruiting

Official Title

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

Medical condition

endometrial cancer

Phase

Phase 2

Healthy volunteers

Study drug

Datopotamab deruxtecan (Dato-DXd), Saruparib, Durvalumab, Capecitabine, 5-Fluorouracil, Volrustomig, Carboplatin, Leucovorin LV, Bevacizumab, Rilvegostomig, Prednisone/ prednisolone

Sex

All

Estimated Enrollment

670

Study type

Interventional

Age

18 Years - 130 Years

Date

Study Start Date: 06 Sept 2022

Estimated Primary Completion Date: 19 Aug 2026

Estimated Study Completion Date: 19 Aug 2026

Study design

Allocation: Non-randomized
Endpoint Classification: -
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment

Verification:

Verified 01 Apr 2024 by AstraZeneca

Collaborators

Daiichi Sankyo

Inclusion and exclusion criteria

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

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

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Arms	Assigned Interventions
Experimental: Substudy-1A Dato-DXd will be evaluated as monotherapy	Drug: Datopotamab deruxtecan (Dato-DXd) Intravenous (IV) Antibody drug conjugate Other Name: DS-1062a
Experimental: Substudy-1B Dato-Dxd in combination with Durvalumab will be evaluated	Drug: Datopotamab deruxtecan (Dato-DXd) Intravenous (IV) Antibody drug conjugate Other Name: DS-1062a Drug: Durvalumab Administered as an IV Other Name: MEDI4736 Other Name: IMFINZI
Experimental: Substudy-1C Dato-Dxd in combination with Saruparib (AZD5305) will be evaluated	Drug: Datopotamab deruxtecan (Dato-DXd) Intravenous (IV) Antibody drug conjugate Other Name: DS-1062a Drug: Saruparib Oral poly ADP ribose polymerase (PARP) inhibitor Other Name: AZD5305
Experimental: Substudy-1D Dato-Dxd in combination with Durvalumab + Saruparib (AZD5305) will be evaluated	Drug: Datopotamab deruxtecan (Dato-DXd) Intravenous (IV) Antibody drug conjugate Other Name: DS-1062a Drug: Saruparib Oral poly ADP ribose polymerase (PARP) inhibitor Other Name: AZD5305 Drug: Durvalumab Administered as an IV Other Name: MEDI4736 Other Name: IMFINZI
Experimental: Substudy-2A Dato-DXd in combination with capecitabine will be evaluated	Drug: Datopotamab deruxtecan (Dato-DXd) Intravenous (IV) Antibody drug conjugate Other Name: DS-1062a Drug: Capecitabine Administered orally Other Name: Xeloda
Experimental: Substudy-2B Dato-DXd in combination with 5-FU will be evaluated	Drug: Datopotamab deruxtecan (Dato-DXd) Intravenous (IV) Antibody drug conjugate Other Name: DS-1062a Drug: 5-Fluorouracil Administered as an IV Other Name: Adrucil
Experimental: Substudy-2C Dato-DXd in combination with chemotherapy (capecitabine or 5-FU) + volrustomig (MEDI5752) will be evaluated	Drug: Datopotamab deruxtecan (Dato-DXd) Intravenous (IV) Antibody drug conjugate Other Name: DS-1062a Drug: Capecitabine Administered orally Other Name: Xeloda Drug: 5-Fluorouracil Administered as an IV Other Name: Adrucil Drug: Volrustomig Administered as an IV Other Name: MEDI5752
Experimental: Substudy-3A Dato-DXd will be evaluated as monotherapy	Drug: Datopotamab deruxtecan (Dato-DXd) Intravenous (IV) Antibody drug conjugate Other Name: DS-1062a
Experimental: Substudy-3B Dato-DXd in combination with Saruparib (AZD5305) will be evaluated	Drug: Datopotamab deruxtecan (Dato-DXd) Intravenous (IV) Antibody drug conjugate Other Name: DS-1062a Drug: Saruparib Oral poly ADP ribose polymerase (PARP) inhibitor Other Name: AZD5305
Experimental: Substudy-3C Dato-DXd will be evaluated in combination with prednisone/prednisolone	Drug: Datopotamab deruxtecan (Dato-DXd) Intravenous (IV) Antibody drug conjugate Other Name: DS-1062a Drug: Prednisone/ prednisolone Administered orally Other Name: Prednisolone
Experimental: Substudy-4A Dato DXd will be evaluated as monotherapy	Drug: Datopotamab deruxtecan (Dato-DXd) Intravenous (IV) Antibody drug conjugate Other Name: DS-1062a
Experimental: Substudy-4B Dato-DXd in combination with carboplatin followed by Dato-DXd + Saruparib (AZD5305) will be evaluated	Drug: Datopotamab deruxtecan (Dato-DXd) Intravenous (IV) Antibody drug conjugate Other Name: DS-1062a Drug: Saruparib Oral poly ADP ribose polymerase (PARP) inhibitor Other Name: AZD5305 Drug: Carboplatin Administered as an IV Other Name: Paraplatin
Experimental: Substudy-5A Dato-DXd will be evaluated as monotherapy	Drug: Datopotamab deruxtecan (Dato-DXd) Intravenous (IV) Antibody drug conjugate Other Name: DS-1062a
Experimental: Substudy-5B Dato-DXd + 5-FU + LV + bevacizumab OR Dato-DXd + capecitabine + bevacizumab will be evaluated	Drug: Datopotamab deruxtecan (Dato-DXd) Intravenous (IV) Antibody drug conjugate Other Name: DS-1062a Drug: Capecitabine Administered orally Other Name: Xeloda Drug: 5-Fluorouracil Administered as an IV Other Name: Adrucil Drug: Leucovorin LV Administered as an IV Other Name: Folinic acid Drug: Bevacizumab Administered as an IV Other Name: Avastin
Experimental: Substudy- 6A Dato-DXd in combination with volrustomig (MEDI5752) will be evaluated	Drug: Datopotamab deruxtecan (Dato-DXd) Intravenous (IV) Antibody drug conjugate Other Name: DS-1062a Drug: Volrustomig Administered as an IV Other Name: MEDI5752
Experimental: Substudy-6B Data-DXd in combination with rilvegostomig (AZD2936) will be evaluated	Drug: Datopotamab deruxtecan (Dato-DXd) Intravenous (IV) Antibody drug conjugate Other Name: DS-1062a Drug: Rilvegostomig Administered as an IV Other Name: AZD2936
Experimental: Substudy- 7A Dato-DXd will be evaluated as monotherapy	Drug: Datopotamab deruxtecan (Dato-DXd) Intravenous (IV) Antibody drug conjugate Other Name: DS-1062a

Documents available

Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

[email protected]

Investigators

Principal Investigator

Global Clinical Lead

AstraZeneca