Bladder CancerNCT06973161
ESPERANZA: External Control Arm Study for T-DXd for Patients With HER2 IHC3+ Solid Tumors
An observational study of Bladder Cancer and Biliary Tract Cancer, run by AstraZeneca at 27 sites in 12 countries.
Trial summary
In DESTINY-Pan-Tumor [DP-02], DESTINY CRC02 [DC-02], and DESTINY-Lung01 [DL-01], T-DXd demonstrated tumor response across a broad range of HER2-expressing solid tumors, particularly IHC3+ patients. Read more about this study
- Who is it for?
- Ages 18 to 130 years
- Conditions the study is for
- Bladder Cancer, Biliary Tract Cancer, Cervical Cancer
- How many people
- 140 participants
- Where
- 27 sitesin 12 countries
- Study dates
- 10 Jun 2025to 17 Mar 2026
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 130 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: The study population of interest is adult patients with HER2 IHC3+ unresectable and/or metastatic disease falling within the indications of interest. All IHC3+ patients who initiated 5.4 mg/kg of T-DXd in DP-02, DC-02, or DL-01 for each indication will be included in the T-Dxd arm of this study. To identify RW SoC patients for each indication, relevant eligibility criteria from the corresponding referent trial will be applied and modified for the RW setting where required.
Who may be able to join
- Male or female patients aged 18 years or older at the time of locally advanced, unresectable or metastatic disease diagnosis.
- Patients diagnosed with one of the following malignancies:
- Locally advanced, unresectable or metastatic colorectal adenocarcinoma, biliary tract, bladder (urothelial), cervical, endometrial, epithelial ovarian, pancreatic, or other solid tumors, or unresectable and/or metastatic non-squamous NSCLC.
- Patients may be included on the basis of de-novo locally advanced, unresectable or metastatic disease diagnosis or progression from initial diagnosis at earlier stages.
- Patients must have received at least one line of prior systemic anti-cancer therapy (SACT) therapy in the advanced/ unresectable/ metastatic setting (i.e. excluding adjuvant/ neoadjuvant SACT) prior to index.
- Index date (start of 2nd or later line SoC systemic anti-cancer therapy (SACT) treatment) for advanced disease occurring between January 2017 and December 2022.
Show all 16Show fewer
- [CRC patients only] Prior treatment at index with at least one of the following in prior lines of therapy:
- Fluoropyrimidine, oxaliplatin, and irinotecan
- Anti-epidermal growth factor receptor (EGFR) treatment, if RAS wild-type
- Anti-vascular endothelial growth factor (VEGF) treatment
- Anti-programmed death-ligand 1 (PD-[L]-1) therapy if tumor is microsatellite instable (MSI)-high/deficient mismatch repair (dMMR), or tumor mutational burden (TMB)-high
- [CRC patients only] BRAF wild-type cancer and confirmed RAS status (either mutant or wild type) identified through testing of the primary tumor or metastatic site at any time following initial diagnosis.
- IHC3+ HER2-expression confirmed through testing of tumor samples taken in the advanced/ recurrent/ metastatic disease stage. The sample taken closest in time prior to the or at start of the index line of therapy should be used to confirm IHC3+ HER2 status. Positive IHC3+ tests may be the result of testing at the time of sampling by the sites or retrospective testing based on archival tumor samples
- ECOG of 0 or 1 (or Karnofsky score of ≥ 70%8), or missing performance status based on most recently recorded information prior to or at index date.
- Patients without recorded history of liver disease, leukaemia, aplastic anaemia or haemophilia at index date.
- Patients known to have died must have a complete recorded date of death.
Who cannot join
- Record of other primary malignancies (except non-melanoma skin cancer) at any time prior to or after index.
- Record of spinal cord compression prior to or at index or active CNS metastases at index (with active CNS metastases determined per physician judgment OR receipt of radiotherapy directed at CNS metastases within 6 months prior to index).
- Record of myocardial infarction within 6 months prior to index date or congestive heart failure at any time prior to or at index date.
- Record of lung-specific intercurrent clinically significant illness based on physician judgement prior to or at index date.
- History of (non-infectious) ILD/ pneumonitis prior to or at index.
- Record of autoimmune, connective tissue or inflammatory disorders prior to or at index date.
Show all 16Show fewer
- Record of complete pneumonectomy prior to or at index date.
- Presence of systemic infection at index date.
- Record of HIV prior to or at index date, or active Hep B or Hep C infection at index date.
- Treatment with T-DXd or DXd-containing ADC at any time prior to or at index.
- Record of pregnancy at or at any time following advanced/ unresectable/ metastatic disease diagnosis.
- Treatment as part of a clinical trial at any time prior to or at index.
- [Pan-tumor patients only] Patients with a record of pleural effusion, ascites or pericardial effusion that requires drainage, peritoneal shunt, or Cell-free and Concentrated Ascites Reinfusion Therapy (CART) at index.
- [Colorectal patients only] Patients with record of leptomeningeal carcinomatosis prior to or at index.
- [NSCLC patients only] Treatment with a HER2-targeted therapy (except for pan-HER class tyrosine kinase inhibitors) at any time prior to or at index.
- [NSCLC patients only] Record of unstable angina at any time prior to or at index date.
Trial locations and contacts
27 sites in 12 countries.
27 sites in 12 countries
France6 sites
Research Site
Caen
Research Site
Lille
Research Site
Marseille
Research Site
Nice
Research Site
Paris
Research Site
Saint-Herblain
Germany5 sites
Research Site
Berlin
Research Site
Essen
Research Site
Frankfurt
Research Site
Heidelberg
Research Site
Würzburg
Spain4 sites
Research Site
Barcelona
Research Site
Madrid
Research Site
Pamplona
Research Site
Valencia
United States2 sites
Research Site
Houston, Texas, 77030
Research Site
Spartanburg, South Carolina, 29303
About this study
Official title: External Control Arm Study for T-DXd for Patients With HER2 IHC3+ Solid Tumors (ESPERANZA)
In DESTINY-Pan-Tumor [DP-02], DESTINY CRC02 [DC-02], and DESTINY-Lung01 [DL-01], T-DXd demonstrated tumor response across a broad range of HER2-expressing solid tumors, particularly IHC3+ patients.
This study will use real-world data (RWD) to identify IHC3+ patients in the real world who received standard of care (SoC) and compare them with IHC3+ patients who received T-DXd in the referent trials. The tumors included are: non-small cell lung cancer [NSCLC], colorectal cancer [CRC], endometrial cancer, bladder cancer, epithelial ovarian cancer, cervical cancer, pancreatic cancer, biliary tract cancers, and other tumors.
Read more
This is a real-world external control arm (ECA) study to generate evidence on the comparative effectiveness of T-DXd versus real-world (RW) SoC in adult patients with HER2 IHC3+ solid tumors who have received prior systemic treatment. HER2 IHC3+ patients who initiated 5.4mg/kg of T-DXd in the referent trials (DP-02, DC-02, and DL-01) will be compared against IHC3+ patients who received RW SoC. This will be a retrospective observational study which will use secondary real-world data and data collected in the 3 aforementioned trials.
Objectives: The primary objective of this study is to evaluate the comparative effectiveness with respect to overall survival (OS) for T-DXd vs SoC for patients with HER2 IHC3+ expressing solid tumors in two pooled cohorts: one cohort reflecting the tumors in the three referent trials (referred to as the 'tumor agnostic' cohort), consisting of patients with NSCLC, CRC, endometrial, epithelial ovarian, cervical, pancreatic, biliary tract cancers, and other tumors; and a second cohort reflecting the tumors in the DP-02 trial (referred to as 'pan tumor'), consisting of the same tumors but excluding NSCLC and CRC.
- Conditions
- Bladder Cancer, Biliary Tract Cancer, Cervical Cancer, Endometrial Cancer, Ovarian Cancer, Pancreatic Cancer
- Medical subject headings
- Urinary Bladder Neoplasms, Biliary Tract Neoplasms, Uterine Cervical Neoplasms, Endometrial Neoplasms, Ovarian Neoplasms, Pancreatic Neoplasms, Colorectal Neoplasms, Lung Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Systemic Anticancer Therapy | Patients who received the existing standard of care systemic anti-cancer therapy (SACT) per routine clinical practice in the real-world setting. | |
| Trastuzumab Deruxtecan | Patients who received 5.4 mg/kg trastuzumab deruxtecan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival
Time from the date of first dose of treatment until the date of death due to any cause.
Measured: Anticipated to be approximately 11 to 17 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 May 2025
- Study start10 Jun 2025
- Primary completion17 Mar 2026
- Study completion17 Mar 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Bladder CancerStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Other
- Time perspective
- Retrospective
- Enrolment
- 140 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Daiichi Sankyo, IQVIA Pty Ltd
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06973161
- Sponsor's protocol ID
- D967VR00001
- Status last verified
- Apr 2026
- First submitted
- 23 Apr 2025
- Last updated
- 8 Apr 2026
- Results posted
- No
- FDA-regulated drug
- No
- Individual data sharing
- Yes: 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. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
Study at a glance
From the registry record, last updated by the sponsor on 8 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- External Control Arm Study for T-DXd for Patients With HER2 IHC3+ Solid Tumors (ESPERANZA)
- ClinicalTrials.gov ID
- NCT06973161
- Acronym / sponsor ID
- D967VR00001
- Conditions
- Bladder Cancer, Biliary Tract Cancer, Cervical Cancer, Endometrial Cancer, Ovarian Cancer, Pancreatic Cancer
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 140 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Collaborators
- Daiichi Sankyo, IQVIA Pty Ltd
- Study start
- 10 Jun 2025 (actual)
- Primary completion
- 17 Mar 2026 (actual)
- Study completion
- 17 Mar 2026 (actual)
- First posted
- 15 May 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In DESTINY-Pan-Tumor [DP-02], DESTINY CRC02 [DC-02], and DESTINY-Lung01 [DL-01], T-DXd demonstrated tumor response across a broad range of HER2-expressing solid tumors, particularly IHC3+ patients.
This study will use real-world data (RWD) to identify IHC3+ patients in the real world who received standard of care (SoC) and compare them with IHC3+ patients who received T-DXd in the referent trials. The tumors included are: non-small cell lung cancer [NSCLC], colorectal cancer [CRC], endometrial cancer, bladder cancer, epithelial ovarian cancer, cervical cancer, pancreatic cancer, biliary tract cancers, and other tumors.
This is a real-world external control arm (ECA) study to generate evidence on the comparative effectiveness of T-DXd versus real-world (RW) SoC in adult patients with HER2 IHC3+ solid tumors who have received prior systemic treatment. HER2 IHC3+ patients who initiated 5.4mg/kg of T-DXd in the referent trials (DP-02, DC-02, and DL-01) will be compared against IHC3+ patients who received RW SoC. This will be a retrospective observational study which will use secondary real-world data and data collected in the 3 aforementioned trials.
Objectives: The primary objective of this study is to evaluate the comparative effectiveness with respect to overall survival (OS) for T-DXd vs SoC for patients with HER2 IHC3+ expressing solid tumors in two pooled cohorts: one cohort reflecting the tumors in the three referent trials (referred to as the 'tumor agnostic' cohort), consisting of patients with NSCLC, CRC, endometrial, epithelial ovarian, cervical, pancreatic, biliary tract cancers, and other tumors; and a second cohort reflecting the tumors in the DP-02 trial (referred to as 'pan tumor'), consisting of the same tumors but excluding NSCLC and CRC.
Study design
- Observational model
- Other
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Systemic Anticancer Therapy | – | –Patients who received the existing standard of care systemic anti-cancer therapy (SACT) per routine clinical practice in the real-world setting. |
| Trastuzumab Deruxtecan | – | –Patients who received 5.4 mg/kg trastuzumab deruxtecan |
Who may qualify
- Ages
- 18 to 130 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- The study population of interest is adult patients with HER2 IHC3+ unresectable and/or metastatic disease falling within the indications of interest. All IHC3+ patients who initiated 5.4 mg/kg of T-DXd in DP-02, DC-02, or DL-01 for each indication will be included in the T-Dxd arm of this study. To identify RW SoC patients for each indication, relevant eligibility criteria from the corresponding referent trial will be applied and modified for the RW setting where required.
Key inclusion criteria (16 listed)
- Male or female patients aged 18 years or older at the time of locally advanced, unresectable or metastatic disease diagnosis.
- Locally advanced, unresectable or metastatic colorectal adenocarcinoma, biliary tract, bladder (urothelial), cervical, endometrial, epithelial ovarian, pancreatic, or other solid tumors, or unresectable and/or metastatic non-squamous NSCLC.
- Patients may be included on the basis of de-novo locally advanced, unresectable or metastatic disease diagnosis or progression from initial diagnosis at earlier stages.
- Patients must have received at least one line of prior systemic anti-cancer therapy (SACT) therapy in the advanced/ unresectable/ metastatic setting (i.e. excluding adjuvant/ neoadjuvant SACT) prior to index.
- Index date (start of 2nd or later line SoC systemic anti-cancer therapy (SACT) treatment) for advanced disease occurring between January 2017 and December 2022.
Key exclusion criteria (16 listed)
- Record of other primary malignancies (except non-melanoma skin cancer) at any time prior to or after index.
- Record of spinal cord compression prior to or at index or active CNS metastases at index (with active CNS metastases determined per physician judgment OR receipt of radiotherapy directed at CNS metastases within 6 months prior to index).
- Record of myocardial infarction within 6 months prior to index date or congestive heart failure at any time prior to or at index date.
- Record of lung-specific intercurrent clinically significant illness based on physician judgement prior to or at index date.
- History of (non-infectious) ILD/ pneumonitis prior to or at index.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Overall Survival
Time frame: Anticipated to be approximately 11 to 17 months
Time from the date of first dose of treatment until the date of death due to any cause.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Apr 2026.
- Individual participant dataSharing planned: Yes. 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. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
27 sites in 12 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Bladder Cancer and Biliary Tract Cancer, run by AstraZeneca at 27 sites in 12 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 27 sites in France, Germany, Spain, United States, Italy and 7 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Survival (time frame: Anticipated to be approximately 11 to 17 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Apr 2026.