Trial record 1 of 1 for:
D926UC00001
Study of Dato-Dxd as Monotherapy and in Combination With Anti-cancer Agents in Patients With Advanced Solid Tumours (TROPION-PanTumor03)
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| ClinicalTrials.gov Identifier: NCT05489211 |
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Recruitment Status :
Recruiting
First Posted : August 5, 2022
Last Update Posted : April 25, 2024
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Sponsor:
AstraZeneca
Collaborator:
Daiichi Sankyo
Information provided by (Responsible Party):
AstraZeneca
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Brief Summary:
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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Endometrial Cancer Gastric Cancer Metastatic Castration-resistant Prostate Cancer Ovarian Cancer Colorectal Cancer Urothelial Cancer Biliary Tract Cancer | Drug: Datopotamab deruxtecan (Dato-DXd) Drug: Saruparib Drug: Durvalumab Drug: Capecitabine Drug: 5-Fluorouracil Drug: Volrustomig Drug: Carboplatin Drug: Leucovorin LV Drug: Bevacizumab Drug: Rilvegostomig Drug: Prednisone/ prednisolone | Phase 2 |
This Phase II, open-label, uncontrolled, multicentre study evaluating the efficacy and safety of Dato-DXd as monotherapy (MONO) and in combination with anticancer agents (COMBO) in various advanced solid tumour types.
This study has a modular design, as such a master protocol with independent substudies enables simultaneous evaluation of the safety profile, recommended Phase II dose (RP2D), and efficacy of Dato-DXd in multiple disease populations and treatment combinations. This study will evaluate various solid tumour types, including endometrial cancer (Substudy 1), gastric cancer (Substudy 2), metastatic castration-resistant prostate cancer (mCRPC) (Substudy 3), ovarian cancer (Substudy 4), colorectal cancer (CRC) (Substudy 5), urothelial cancer (Substudy 6) and biliary tract cancer (Substudy 7) in the advanced or metastatic setting. Within each substudy, Dato-DXd will be evaluated as monotherapy (for all substudies except Substudy 2 (Gastric Cancer) and Substudy 6 (Urothelial Cancer) and in combination with approved or novel anticancer agents that may be active in the tumour type being evaluated (for all substudies except Substudy 7).
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 531 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Parallel Assignment |
| Intervention Model Description: | 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. Substudy 1 (Endometrial): MONO: Dato-DXd monotherapy; COMBO; Dato-DXd + durvalumab, Dato-DXd + Saruparib, Dato-DXd + durvalumab +Saruparib Substudy 2 (Gastric): Dato-DXd + capecitabine, Dato-DXd + 5-FU, Dato-DXd + capecitabine/ 5-FU + volrustomig Substudy 3 (mCRPC): MONO; COMBO: Dato-DXd + AZD5305, Dato-DXd + prednisone/prednisolone Substudy 4 (Ovarian): MONO; COMBO: Dato-DXd + carboplatin --> Dato-DXd + Saruparib Substudy 5 (CRC): MONO; COMBO Dato-DXd + 5-FU + leucovorin + bevacizumab or Dato-DXd + capecitabine + bevacizumab Substudy 6 (Urothelial): Dato-DXd + volrustomig, Dato-DXd + rilvegostomig Substudy 7 (BTC): MONO |
| Masking: | None (Open Label) |
| Masking Description: | The study is open label. Patients will be assigned treatment in all Substudies. |
| Primary Purpose: | Treatment |
| 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 |
| Actual Study Start Date : | September 6, 2022 |
| Estimated Primary Completion Date : | August 19, 2026 |
| Estimated Study Completion Date : | August 19, 2026 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
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Experimental: Substudy-1A
Dato-DXd will be evaluated as monotherapy
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Drug: Datopotamab deruxtecan (Dato-DXd)
Intravenous (IV) Antibody drug conjugate
Other Name: DS-1062a |
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Experimental: Substudy-1B
Dato-Dxd in combination with Durvalumab will be evaluated
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Drug: Datopotamab deruxtecan (Dato-DXd)
Intravenous (IV) Antibody drug conjugate
Other Name: DS-1062a Drug: Durvalumab Administered as an IV
Other Names:
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Experimental: Substudy-1C
Dato-Dxd in combination with Saruparib (AZD5305) will be evaluated
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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 |
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Experimental: Substudy-1D
Dato-Dxd in combination with Durvalumab + Saruparib (AZD5305) will be evaluated
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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 Names:
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Experimental: Substudy-2A
Dato-DXd in combination with capecitabine will be evaluated
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Drug: Datopotamab deruxtecan (Dato-DXd)
Intravenous (IV) Antibody drug conjugate
Other Name: DS-1062a Drug: Capecitabine Administered orally
Other Name: Xeloda |
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Experimental: Substudy-2B
Dato-DXd in combination with 5-FU will be evaluated
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Drug: Datopotamab deruxtecan (Dato-DXd)
Intravenous (IV) Antibody drug conjugate
Other Name: DS-1062a Drug: 5-Fluorouracil Administered as an IV
Other Name: Adrucil |
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Experimental: Substudy-2C
Dato-DXd in combination with chemotherapy (capecitabine or 5-FU) + volrustomig (MEDI5752) will be evaluated
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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 |
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Experimental: Substudy-3A
Dato-DXd will be evaluated as monotherapy
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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
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Drug: Datopotamab deruxtecan (Dato-DXd)
Intravenous (IV) Antibody drug conjugate
Other Name: DS-1062a Drug: Prednisone/ prednisolone Administered orally
Other Name: Prednisolone |
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Experimental: Substudy-4A
Dato DXd will be evaluated as monotherapy
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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
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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 |
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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 |
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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
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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 |
Primary Outcome Measures :
- Objective response rate (ORR) [ Time Frame: From baseline to progressive disease or death (approximately 1 year) ]Proportion of participants who have a confirmed CR or confirmed PR, as determined by the investigator at local site per RECIST 1.1.
- The number of subjects with adverse events/serious adverse events [ Time Frame: Throughout the treatment and the safety follow-up period 28 [+ 7] days after the discontinuation of all study interventions, except durvalumab, nivolumab, and bevacizumab for which it will be 90 [+ 7] days (approximatelt 1 year) ]Number of patients with adverse events and with serious adverse events including abnormal clinical observations, abnormal Electrocardiogram (ECG) parameters, abnormal laboratory assessments and abnormal vital signs that changed from baseline.
- PSA50 response (Substudy 3 only) [ Time Frame: Time to PSA progression is defined as the time from randomization to PSA progression per PCWG3 criteria (up to 12 weeks) ]Proportion of participants achieving a ≥ 50% decrease in PSA from baseline to the lowest post-baseline PSA result, confirmed by a second consecutive PSA assessment at least 3 weeks later.
Secondary Outcome Measures :
- Progression free survival (PFS) [ Time Frame: From baseline to progressive disease or death (approximately 1 year) ]PFS is defined as time from start of treatment until progression per RECIST 1.1 as assessed by the investigator.
- Duration Of Response (DOR) [ Time Frame: From baseline to progressive disease or death (approximately 1 year) ]DoR is defined as the time from the date of first documented confirmed response until date of documented progression per RECIST 1.1 as assessed by the investigator or death.
- Disease Control Rate (DCR) [ Time Frame: at 12 and 24 weeks ]DCR at 12 and 24 weeks is defined as the percentage of participants who have a Complete response (CR) or Partial response (PR) in the first 13 and 25 weeks or who have Stable disease (SD) for at least 11 and 23 weeks after the date of first dose respectively, per RECIST 1.1 as assessed by the investigator at local site and derived from the raw tumour data.
- Best percentage change in tumour size [ Time Frame: From baseline to progressive disease or death (approximately 1 year) ]The best percentage change from baseline in tumour size will be derived as the maximum reduction from baseline or (in the absence of reduction) the minimum increase from baseline.
- Anti Drug Antibody (ADA) for Dato-DXd (all substudies), Durvalumab (substudy 1), volrustomig and rilvegostomig (substudy 6) [ Time Frame: Throughout the treatment period at pre-defined intervals and including the safety follow-up period (approximately 1 year) ]Whole blood samples for determination of ADA in plasma will be collected; Percentage of patients who develop ADA
- Pharmacokinetics of Dato-DXd (all substudies), durvalumab (substudy 1) and AZD5305 (substudy 1, substudy 3, substudy 4), volrustomig and rilvegostomig (substudy 6): Maximum plasma concentration of the drug (Cmax) [ Time Frame: At predefined intervals throughout the treatment period (approximately 1 year) ]The concentration in plasma will be determined.
- Pharmacokinetics of Dato-DXd (all substudies), durvalumab (substudy 1) and AZD5305 (substudy 1, substudy 3, substudy 4), volrustomig and rilvegostomig (substudy 6): The time taken to reach the maximum concentration (Tmax) [ Time Frame: At predefined intervals throughout the treatment period (approximately 1 year) ]The concentration in plasma will be determined.
- Pharmacokinetic Parameter of Dato-DXd (all substudies), durvalumab (substudy 1) and AZD5305 (substudy 1, substudy 3, substudy 4), volrustomig and rilvegostomig (substudy 6): Area under the plasma concentration- time curve (AUC) [ Time Frame: At predefined intervals throughout the treatment period (approximately 1 year) ]The concentration in plasma will be determined. Area under the curve is the integral of the concentration-time curve. The AUC reflects the actual body exposure to drug after administration. The AUC is dependent on the rate of elimination of the drug from the body and the dose administered.
- Plasma concentration of Total anti-TROP2 antibody [ Time Frame: Throughout the treatment period at pre-defined intervals (approximately 1 year) ]Expression of TROP2 will be measured in blood sample
- Plasma concentration of MAAA-1181a [ Time Frame: Throughout the treatment period at pre-defined intervals (approximately 1 year) ]The concentration in plasma will be determined (Cmax will be derived).
- Radiographic PFS (substudy 3) [ Time Frame: From baseline to radiographic progression or death (approximately 1 year) ]PFS is defined as time from start of treatment until radiographic progression per RECIST 1.1 (soft tissue) and/or PCWG3 criteria (bone) as assessed by the investigator or death.
- Overall survival (OS) (substudy 4) [ Time Frame: From baseline to death (approximately 1 year) ]OS is defined as time from start of treatment until death.
- CA-125 response (Substudy 4) [ Time Frame: From baseline to CA-125 response evaluated according to the GCIG criteria (up to 12 weeks) ]Proportion of participants achieving a > 50% reduction in CA-125 levels from a pre-treatment sample confirmed and maintained for at least 28 days.
Information from the National Library of Medicine
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years to 130 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05489211
Contacts
| Contact: AstraZeneca Clinical Study Information Center | 1-877-240-9479 | information.center@astrazeneca.com |
Locations
Show 95 study locations
Sponsors and Collaborators
AstraZeneca
Daiichi Sankyo
Investigators
| Principal Investigator: | Global Clinical Lead, MD | AstraZeneca |
| Responsible Party: | AstraZeneca |
| ClinicalTrials.gov Identifier: | NCT05489211 |
| Other Study ID Numbers: |
D926UC00001 2022-000776-19 ( EudraCT Number ) |
| First Posted: | August 5, 2022 Key Record Dates |
| Last Update Posted: | April 25, 2024 |
| Last Verified: | April 2024 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. |
| Supporting Materials: |
Study Protocol Statistical Analysis Plan (SAP) |
| Time Frame: | AstraZeneca will meet or exceed data availability as per the commitments made to the European Federation of Pharmaceutical Industries and Associations (EFPIA) Pharma Data Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. |
| Access Criteria: | When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. |
| URL: | https://astrazenecagroup-dt.pharmacm.com/DT/Home |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by AstraZeneca:
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TROPION-PanTumor03 Datopotamab Deruxtecan (Dato-DXd) Solid Tumours Antibody-drug conjugate (ADC) Trophoblast cell surface protein 2 (TROP2) |
Additional relevant MeSH terms:
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Endometrial Neoplasms Biliary Tract Neoplasms Urogenital Neoplasms Neoplasms by Site Neoplasms Genital Diseases Urogenital Diseases Digestive System Neoplasms Digestive System Diseases Genital Diseases, Female Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Genital Neoplasms, Female Uterine Neoplasms Uterine Diseases |
Biliary Tract Diseases Leucovorin Prednisone Prednisolone Methylprednisolone Acetate Methylprednisolone Methylprednisolone Hemisuccinate Prednisolone acetate Bevacizumab Durvalumab Carboplatin Capecitabine Fluorouracil Prednisolone hemisuccinate Prednisolone phosphate |