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

NCT06973161 | Completed

• 1 other identifier: D967VR00001
• Study Type: observational
• Target: 140
• Locations: 12 countries
• Sites: 27

Brief 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.

Conditions

Endometrial Cancer; Bladder Cancer; Biliary Tract Cancer; Lung Cancer; Cervical Cancer; Ovarian Cancer; Pancreatic Cancer; Colorectal Cancer; Other Tumors

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  Time from the date of first dose of treatment until the date of death due to any cause.

  Anticipated to be approximately 11 to 17 months

Study Arms (2)

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

Eligibility Criteria

• Age: 18 Years - 130 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

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.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AstraZeneca: lead
• Daiichi Sankyo: collaborator
• IQVIA Pty Ltd: collaborator

Study Sites (27)

Research Site

Spartanburg, South Carolina, 29303, United States

Location

Research Site

Houston, Texas, 77030, United States

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Vienna, Austria

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Liège, Belgium

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London, Ontario, N6A 5A5, Canada

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Olomouc, Czechia

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Copenhagen, Denmark

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Caen, France

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Lille, France

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Marseille, France

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Nice, France

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Paris, France

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Saint-Herblain, France

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Berlin, Germany

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Essen, Germany

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Frankfurt, Germany

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Heidelberg, Germany

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Würzburg, Germany

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Meldola, Italy

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Rome, Italy

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Porto, Portugal

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Barcelona, Spain

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Madrid, Spain

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Pamplona, Spain

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Valencia, Spain

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Leeds, United Kingdom

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London, United Kingdom

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MeSH Terms

Conditions

Urinary Bladder Neoplasms; Biliary Tract Neoplasms; Uterine Cervical Neoplasms; Endometrial Neoplasms; Ovarian Neoplasms; Pancreatic Neoplasms; Colorectal Neoplasms; Lung Neoplasms

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Digestive System Neoplasms; Biliary Tract Diseases; Digestive System Diseases; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Genital Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Endocrine System Diseases; Gonadal Disorders; Pancreatic Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: RETROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 23, 2025
• First Posted: May 15, 2025
• Study Start: June 10, 2025
• Primary Completion: March 17, 2026
• Study Completion: March 17, 2026
• Last Updated: April 8, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. For details of our timelines, please rerefer 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 anonymized individual patient-level data via secure research environment Vivli.org. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Locations

DE (5); US (2); AU (1); ES (4); GB (2); FR (6); IT (2); PT (1); BE (1); DK (1); CA (1); CZ (1)