External Control Arm Study for T-DXd for Patients With HER2 IHC3+ Solid Tumors (ESPERANZA)

Plain English Summary

ESPERANZA: External Control Arm Study for T-DXd for Patients With HER2 IHC3+ Solid Tumors is a Not Applicable clinical trial sponsored by AstraZeneca studying Bladder Cancer, Biliary Tract Cancer, Cervical Cancer, Endometrial Cancer, Ovarian Cancer, Pancreatic Cancer, Colorectal Cancer, Lung Cancer, Other Tumors. This study compares a targeted therapy called T-DXd to standard treatments for patients with certain solid tumors that have a specific marker (HER2 IHC3+). It is designed for adults with various advanced solid tumors, including bladder, biliary tract, cervical, endometrial, ovarian, pancreatic, colorectal, and lung cancers, who have previously received at least one line of cancer therapy. Participation involves using existing medical records (real-world data) to compare outcomes; patients are not actively receiving treatment in this specific study. The alternative is receiving standard of care treatments as determined by a patient's doctor. The trial aims to enroll 140 participants.

Official 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. 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.

Who Can Participate

Here is what you need to know about eligibility for this trial. Adults aged 18 and older with specific advanced solid tumors (bladder, biliary tract, cervical, endometrial, ovarian, pancreatic, colorectal, non-squamous non-small cell lung cancer) that test positive for HER2 at the IHC3+ level. Patients must have received at least one prior systemic cancer therapy for their advanced disease. Individuals with a history of certain other cancers, active brain metastases, significant heart problems, or certain lung conditions may not be eligible. Patients who have previously received T-DXd or similar drugs are excluded. This trial is studying Bladder Cancer, Biliary Tract Cancer, Cervical Cancer, Endometrial Cancer, Ovarian Cancer, Pancreatic Cancer, Colorectal Cancer, Lung Cancer, Other Tumors, so participants generally need a confirmed diagnosis.

What They're Measuring

The primary outcome of overall survival means researchers will look at how long patients live after starting treatment, helping to understand if T-DXd or standard care leads to longer life for patient The specific primary outcome measures are: Overall Survival (Anticipated to be approximately 11 to 17 months). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This study does not have a traditional clinical phase designation. It may be an observational study that follows patients without intervening in their care, an expanded access or compassionate use program, or other non-interventional research. These studies contribute valuable data about disease progression, treatment patterns, and patient outcomes.

Why This Trial Matters

This trial is important because it aims to provide real-world evidence on how well T-DXd works compared to standard treatments for a specific group of patients with HER2-positive solid tumors, potenti This research targets Bladder Cancer, Biliary Tract Cancer, Cervical Cancer, Endometrial Cancer, Ovarian Cancer, Pancreatic Cancer, Colorectal Cancer, Lung Cancer, Other Tumors, where improved treatment options are needed.

Investor Insight

This study leverages real-world data to support the use of T-DXd in a broader patient population with HER2 IHC3+ solid tumors, potentially strengthening its market position against existing standard o

Is This Trial Right for Me?

Ask your doctor if your tumor is HER2 IHC3+ and if T-DXd is a potential treatment option for you. Understand that this study uses your past medical information; you will not be receiving new treatment as part of this specific trial. Discuss any concerns about your medical history, such as heart conditions or lung issues, with your doctor, as these could affect eligibility. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: OBSERVATIONAL
• Enrollment: 140 participants

Primary Outcomes

• Overall Survival (Anticipated to be approximately 11 to 17 months)

Full Eligibility Criteria

Inclusion Criteria (for the ECA):

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.

\[CRC patients only\] 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.

Exclusion Criteria (for the ECA):

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.

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

• Research Site, Spartanburg, South Carolina, United States
• Research Site, Houston, Texas, United States
• Research Site, Vienna, Austria
• Research Site, Liège, Belgium
• Research Site, London, Ontario, Canada
• Research Site, Olomouc, Czechia
• Research Site, Copenhagen, Denmark
• Research Site, Caen, France
• Research Site, Lille, France
• Research Site, Marseille, France
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Bladder Cancer
• Biliary Tract Cancer
• Cervical Cancer
• Endometrial Cancer
• Ovarian Cancer
• Pancreatic Cancer
• Colorectal Cancer
• Lung Cancer
• Solid Tumors
• HER2-Positive Cancers

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